Molecules

2020

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10 pages, 1200 KiB

Open AccessArticle

Simplified LC-MS Method for Analysis of Sterols in Biological Samples

by Cene Skubic, Irena Vovk, Damjana Rozman and Mitja Križman

Molecules 2020, 25(18), 4116; https://doi.org/10.3390/molecules25184116 - 9 Sep 2020

Cited by 19 | Viewed by 5144

Abstract

We developed a simple and robust liquid chromatographic/mass spectrometric method (LC-MS) for the quantitative analysis of 10 sterols from the late part of cholesterol synthesis (zymosterol, dehydrolathosterol, 7-dehydrodesmosterol, desmosterol, zymostenol, lathosterol, FFMAS, TMAS, lanosterol, and dihydrolanosterol) from cultured human hepatocytes in a single [...] Read more.

We developed a simple and robust liquid chromatographic/mass spectrometric method (LC-MS) for the quantitative analysis of 10 sterols from the late part of cholesterol synthesis (zymosterol, dehydrolathosterol, 7-dehydrodesmosterol, desmosterol, zymostenol, lathosterol, FFMAS, TMAS, lanosterol, and dihydrolanosterol) from cultured human hepatocytes in a single chromatographic run using a pentafluorophenyl (PFP) stationary phase. The method also avails on a minimized sample preparation procedure in order to obtain a relatively high sample throughput. The method was validated on 10 sterol standards that were detected in a single chromatographic LC-MS run without derivatization. Our developed method can be used in research or clinical applications for disease-related detection of accumulated cholesterol intermediates. Disorders in the late part of cholesterol synthesis lead to severe malformation in human patients. The developed method enables a simple, sensitive, and fast quantification of sterols, without the need of extended knowledge of the LC-MS technique, and represents a new analytical tool in the rising field of cholesterolomics. Full article

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11 pages, 4537 KiB

Open AccessArticle

Two New Apotirucallane-Type Triterpenoids from the Pericarp of Toona sinensis and Their Ability to Reduce Oxidative Stress in Rat Glomerular Mesangial Cells Cultured under High-Glucose Conditions

by Di Liu, Rong-shen Wang, Lu-lu Xuan, Xiao-hong Wang and Wan-zhong Li

Molecules 2020, 25(4), 801; https://doi.org/10.3390/molecules25040801 - 12 Feb 2020

Cited by 10 | Viewed by 2913

Abstract

Hyperglycemia is a strong risk factor for chronic complications of diabetes. Hyperglycemic conditions foster not only the production of reactive oxygen species (ROS), but also the consumption of antioxidants, leading to oxidative stress and promoting the occurrence and progression of complications. During our [...] Read more.

Hyperglycemia is a strong risk factor for chronic complications of diabetes. Hyperglycemic conditions foster not only the production of reactive oxygen species (ROS), but also the consumption of antioxidants, leading to oxidative stress and promoting the occurrence and progression of complications. During our continuous search for antioxidant constituents from the pericarp of Toona sinensis (A. Juss.) Roem, we isolated two previously unreported apotirucallane-type triterpenoids, toonasinensin A (1) and toonasinensin B (2), together with five known apotirucallane-type triterpenoids (3–7) and two known cycloartane-type triterpenoids (8–9) from the pericarp. Compounds 8–9 were obtained from T. sinensis for the first time. Their structures were characterized based on interpretation of spectroscopic data (1D, 2D NMR, high-resolution electrospray ionization mass spectra, HR-ESI-MS) and comparison to previous reports. Compounds (2, 4, 6, 7, and 9) were able to inhibit proliferation against rat glomerular mesangial cells (GMCs) cultured under high-glucose conditions within a concentration of 80 μM. Compounds (2, 6, and 7) were tested for antioxidant activity attributable to superoxide dismutase (SOD), malondialdehyde (MDA), and ROS in vitro, and the results showed that compounds (2, 6, and 7) could significantly increase the levels of SOD and reduce the levels of MDA and ROS. The current studies showed that apotirucallane-type triterpenoids (2, 6, and 7) might have the antioxidant effects against diabetic nephropathy. Full article

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2019

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16 pages, 876 KiB

Open AccessReview

Review of Ginseng Anti-Diabetic Studies

by Wei Chen, Prabhu Balan and David G. Popovich

Molecules 2019, 24(24), 4501; https://doi.org/10.3390/molecules24244501 - 9 Dec 2019

Cited by 94 | Viewed by 11889

Abstract

Ginseng is one of the most valuable and commonly used Chinese medicines not only in ancient China but also worldwide. Ginsenosides, also known as saponins or triterpenoids, are thought to be responsible for the beneficial effects of ginseng. In this review, we summarize [...] Read more.

Ginseng is one of the most valuable and commonly used Chinese medicines not only in ancient China but also worldwide. Ginsenosides, also known as saponins or triterpenoids, are thought to be responsible for the beneficial effects of ginseng. In this review, we summarize recent publications on anti-diabetic studies of ginseng extracts and ginsenosides in cells, animals, and humans. It seems that the anti-diabetic effect of ginseng is positive for type 2 diabetic patients but has no significant impact on prediabetes or healthy adults. Regulation of insulin secretion, glucose uptake, anti-oxidative stress, and anti-inflammatory pathways may be the mechanisms involved with ginseng’s anti-diabetic effects. Taken together, this summary provides evidence for the anti-diabetes effects of ginseng extracts and ginsenosides as well as the underlying mechanisms of their impact on diabetes. Full article

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29 pages, 1158 KiB

Open AccessReview

Saponins from Quillaja saponaria and Quillaja brasiliensis: Particular Chemical Characteristics and Biological Activities

by Juliane Deise Fleck, Andresa Heemann Betti, Francini Pereira Da Silva, Eduardo Artur Troian, Cristina Olivaro, Fernando Ferreira and Simone Gasparin Verza

Molecules 2019, 24(1), 171; https://doi.org/10.3390/molecules24010171 - 4 Jan 2019

Cited by 96 | Viewed by 14453

Abstract

Quillaja saponaria Molina represents the main source of saponins for industrial applications. Q. saponaria triterpenoids have been studied for more than four decades and their relevance is due to their biological activities, especially as a vaccine adjuvant and immunostimulant, which have led to [...] Read more.

Quillaja saponaria Molina represents the main source of saponins for industrial applications. Q. saponaria triterpenoids have been studied for more than four decades and their relevance is due to their biological activities, especially as a vaccine adjuvant and immunostimulant, which have led to important research in the field of vaccine development. These saponins, alone or incorporated into immunostimulating complexes (ISCOMs), are able to modulate immunity by increasing antigen uptake, stimulating cytotoxic T lymphocyte production (Th1) and cytokines (Th2) in response to different antigens. Furthermore, antiviral, antifungal, antibacterial, antiparasitic, and antitumor activities are also reported as important biological properties of Quillaja triterpenoids. Recently, other saponins from Q. brasiliensis (A. St.-Hill. & Tul.) Mart. were successfully tested and showed similar chemical and biological properties to those of Q. saponaria barks. The aim of this manuscript is to summarize the current advances in phytochemical and pharmacological knowledge of saponins from Quillaja plants, including the particular chemical characteristics of these triterpenoids. The potential applications of Quillaja saponins to stimulate further drug discovery research will be provided. Full article

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2018

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10 pages, 1648 KiB

Open AccessArticle

The Increase of Triterpene Saponin Production Induced by Trans-Anethole in Hairy Root Cultures of Panax quinquefolium

by Ewa Kochan, Piotr Szymczyk, Łukasz Kuźma, Grażyna Szymańska, Anna Wajs-Bonikowska, Radosław Bonikowski and Monika Sienkiewicz

Molecules 2018, 23(10), 2674; https://doi.org/10.3390/molecules23102674 - 17 Oct 2018

Cited by 27 | Viewed by 4110

Abstract

In vitro cultivation is an effective way to increase pharmaceutical production. To increase ginsenoside production in hairy root cultures of American ginseng, the present study uses trans-anethole as an elicitor. The content of nine triterpene saponins was determined: Rb1, Rb2, Rb3, Rc, [...] Read more.

In vitro cultivation is an effective way to increase pharmaceutical production. To increase ginsenoside production in hairy root cultures of American ginseng, the present study uses trans-anethole as an elicitor. The content of nine triterpene saponins was determined: Rb1, Rb2, Rb3, Rc, Rd, Rg1, Rg2, Re and Rf. Trans-anethole was found to stimulate saponin synthesis regardless of exposure time (24 and 72 h). Twenty-four hour exposure to 1 μmol trans-anethole in the culture medium resulted in the highest increase of total saponin content (twice that of untreated roots), and optimum accumulation of Rb-group saponins, with ginsenoside Rc dominating (8.45 mg g⁻¹ d.w.). In contrast, the highest mean content of protopanaxatriol derivatives was obtained for 10 μmol trans-anethole. The Re metabolite predominated, reaching a concentration of 5.72 mg g⁻¹ d.w.: a 3.9-fold increase over untreated roots. Elicitation with use of trans-anethole can therefore be an effective method of increasing ginsenoside production in shake flasks. Full article

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12 pages, 1919 KiB

Open AccessFeature PaperArticle

Optimization of Culture Condition for Ganoderic Acid Production in Ganoderma lucidum Liquid Static Culture and Design of a Suitable Bioreactor

by Gaosheng Hu, Manhuayun Zhai, Rong Niu, Xiaoqiang Xu, Qian Liu and Jingming Jia

Molecules 2018, 23(10), 2563; https://doi.org/10.3390/molecules23102563 - 8 Oct 2018

Cited by 20 | Viewed by 6833

Abstract

Ganoderma lucidum, a famous medicinal mushroom used worldwide, is a rich source of triterpenoids which, together with polysaccharides, are believed to be the main effective constituents of G. lucidum. With the increase of market demand, the wild resource is facing serious [...] Read more.

Ganoderma lucidum, a famous medicinal mushroom used worldwide, is a rich source of triterpenoids which, together with polysaccharides, are believed to be the main effective constituents of G. lucidum. With the increase of market demand, the wild resource is facing serious limitations, and the quality of cultivated fruiting bodies can be seriously affected by the availability of wood resources and by cultivation management practices. In the present study, we aimed to develop an alternative way to produce useful triterpenoids from G. lucidum. We cultured the strain using a two-stage liquid culture strategy and investigated the effects of nitrogen limitation, carbon supply, static culture volume and air supply in the static culture stage on the accumulation of five triterpenoids (GA-P, GA-Q, GA-T, GA-S, GA-R). Our results showed that, under optimized condition, the total yield of the five triterpenoids reached 963 mg/L (as determined by HPLC). Among the five triterpenoids, GA-T accounted for about 75% of the total yield. Besides, a bioreactor suitable for fungal liquid static culture with a 10 L extensible plastic bag shaped culture unit was designed and in which the maximum total yield of the five GAs reached 856.8 mg/L, and the GAs content reached 5.99%. Our results demonstrate the potential of industrial application of G. lucidum culture for the production of triterpenoids, especially GA-T. Air supply significantly improved the accumulation of triterpenoids, and this will provide important clues to understand why more triterpenoids are produced in the mycelia mat under static liquid culture conditions. Full article

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7 pages, 1214 KiB

Open AccessArticle

Isolation, Structural Elucidation of Three New Triterpenoids from the Stems and Leaves of Schisandra chinensis (Turcz) Baill.

by Feng Qiu, Han Liu, Huan Duan, Pian Chen, Shao-Juan Lu, Guang-Zhong Yang and Xin-Xiang Lei

Molecules 2018, 23(7), 1624; https://doi.org/10.3390/molecules23071624 - 4 Jul 2018

Cited by 27 | Viewed by 4558

Abstract

Schisandra chinensis (Turcz) Baill. is sufficiently well known as a medicinal plant worldwide, which modern research shows has many pharmacological activities such as hepatoprotective, anti-inflammatory effect, potent anti-HIV-1 activity, anti-tumor effect, and activity on the central nervous system. With considerable chemical investigation, three [...] Read more.

Schisandra chinensis (Turcz) Baill. is sufficiently well known as a medicinal plant worldwide, which modern research shows has many pharmacological activities such as hepatoprotective, anti-inflammatory effect, potent anti-HIV-1 activity, anti-tumor effect, and activity on the central nervous system. With considerable chemical investigation, three new triterpenoids (1–3), together with four known triterpenoids were isolated from the S. chinensis (Turcz) Baill. Their structures were elucidated by 1D- and 2D-NMR spectroscopic analyses, single-crystal X-ray diffraction and high-resolution mass spectroscopy, which were identified as Schisanlactone I (1), Schinalactone D, (2), Schisanlactone J, (3) Kadsuphilactone B (4), Schisanlactone C (5), Schisphendilactone B (6), and Schinchinenlactone A (7). The cytotoxicity of those compounds (1–7) was tested against Hep-G2 cell lines, but no apparent antitumor activity was observed at 50 µg/mL using MTT method. Full article

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2016

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942 KiB

Open AccessArticle

Six New Triterpene Derivatives from Aralia chinensis Var. dasyphylloides

by Rui-xi Gao, Maochuan Liao, Xianju Huang, Yu Chen, Guangzhong Yang and Jun Li

Molecules 2016, 21(12), 1700; https://doi.org/10.3390/molecules21121700 - 9 Dec 2016

Cited by 6 | Viewed by 4871

Abstract

Aralia chinensis var. dasyphylloides is widely distributed in China and used as a traditional herbal medicine for the treatment of digestive and immune system diseases. The present study aimed to search for novel oleanolic-type triterpenoids in low-polarity fractions. Six new triterpene derivatives ( [...] Read more.

Aralia chinensis var. dasyphylloides is widely distributed in China and used as a traditional herbal medicine for the treatment of digestive and immune system diseases. The present study aimed to search for novel oleanolic-type triterpenoids in low-polarity fractions. Six new triterpene derivatives (1–6), together with two known compounds were isolated from the barks of A. chinensis var. dasyphylloides. Their structures were elucidated by 1D- and 2D-NMR spectroscopic analysis and chemical methods. They were identified as 3-oxo-oleana-11,13(18)-dien-28,30-dioic acid (1), 30-hydroxy-3-oxo-oleana-11,13(18)-dien-28-oic acid (2), 3β-hydroxy-oleana-11,13(18)-dien-28-oic acid-28-O-β-d-glucopyranoside (3), 3β,30-dihydroxy-oleana-11,13(18)-dien-28-oic acid-28-O-β-d-glucopyranoside (4), 3β-hydroxy-oleana-11,13(18)-dien-28-oic acid-3-O-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranoside (5), 3β,29-dihydroxy-oleana-9(11),12-dien-28-oic acid-28-O-β-d-glucopyranoside (6), namely, araliachinolic acids I and II and araliachinosides I–IV. The cytotoxicity of the isolated compounds was tested against HepG2, A549, SGC7901, and MCF7 cell lines, but no apparent activity was observed at a concentration of 50 μM. Full article

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2684 KiB

Open AccessArticle

Screening for Triterpenoid Saponins in Plants Using Hyphenated Analytical Platforms

by Bekzod Khakimov, Li Hong Tseng, Markus Godejohann, Søren Bak and Søren Balling Engelsen

Molecules 2016, 21(12), 1614; https://doi.org/10.3390/molecules21121614 - 24 Nov 2016

Cited by 29 | Viewed by 10483

Abstract

Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene [...] Read more.

Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene aglycone with one or more sugar moieties attached to it. However, due to similar physico-chemical properties, isolation and identification of a large diversity of triterpenoid saponins remain challenging. This study demonstrates a methodology to screen saponins using hyphenated analytical platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and pubescent (P) type that are known to differ by their insect resistance. The proposed methodology allows for detailed comparison of saponin profiles from intact plant extracts as well as saponin aglycone profiles from hydrolysed samples. Continuously measured 1D proton NMR data during LC separation along with mass spectrometry data revealed significant differences, including contents of saponins, types of aglycones and numbers of sugar moieties attached to the aglycone. A total of 49 peaks were tentatively identified as saponins from both plants; they are derived from eight types of aglycones and with 2–5 sugar moieties. Identification of two previously known insect-deterrent saponins, hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the applicability of the methodology for relatively rapid screening of bioactive compounds. Full article

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2705 KiB

Open AccessReview

Chemical Components and Pharmacological Activities of Terpene Natural Products from the Genus Paeonia

by Dan-Dan Zhao, Li-Li Jiang, Hong-Yi Li, Peng-Fei Yan and Yan-Long Zhang

Molecules 2016, 21(10), 1362; https://doi.org/10.3390/molecules21101362 - 13 Oct 2016

Cited by 50 | Viewed by 9653

Abstract

Paeonia is the single genus of ca. 33 known species in the family Paeoniaceae, found in Asia, Europe and Western North America. Up to now, more than 180 compounds have been isolated from nine species of the genus Paeonia, including terpenes, [...] Read more.

Paeonia is the single genus of ca. 33 known species in the family Paeoniaceae, found in Asia, Europe and Western North America. Up to now, more than 180 compounds have been isolated from nine species of the genus Paeonia, including terpenes, phenols, flavonoids, essential oil and tannins. Terpenes, the most abundant naturally occurring compounds, which accounted for about 57% and occurred in almost every species, are responsible for the observed in vivo and in vitro biological activities. This paper aims to give a comprehensive overview of the recent phytochemical and pharmacological knowledge of the terpenes from Paeonia plants, and enlighten further drug discovery research. Full article

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4312 KiB

Open AccessReview

Methodology for the Construction of the Bicyclo[4.3.0]nonane Core

by Nicholas A. Eddy and Pranjali Ichalkaranje

Molecules 2016, 21(10), 1358; https://doi.org/10.3390/molecules21101358 - 12 Oct 2016

Cited by 10 | Viewed by 10659

Abstract

The bicyclo[4.3.0]nonane scaffold, commonly known as a hydrindane, is a common structural motif found in many terpenoid structures and one that remains a challenge for synthetic chemists to elaborate with appropriate regio- and stereo-selectivity. Over the course of the study of terpene natural [...] Read more.

The bicyclo[4.3.0]nonane scaffold, commonly known as a hydrindane, is a common structural motif found in many terpenoid structures and one that remains a challenge for synthetic chemists to elaborate with appropriate regio- and stereo-selectivity. Over the course of the study of terpene natural products, the elaboration of the hydrindane structure has seen progress on the utilization of both old and newer methods to achieve the desired outcomes. This review seeks to serve as a general overview of these methods, and detail specific examples. Full article

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433 KiB

Open AccessCommunication

Quantitative Determination of 3-O-Acetyl-11-Keto-βBoswellic Acid (AKBA) and Other Boswellic Acids in Boswellia sacra Flueck (syn. B. carteri Birdw) and Boswellia serrata Roxb

by Giuseppe Mannino, Andrea Occhipinti and Massimo E. Maffei

Molecules 2016, 21(10), 1329; https://doi.org/10.3390/molecules21101329 - 6 Oct 2016

Cited by 58 | Viewed by 9745

Abstract

Boswellia serrata and Boswellia sacra (syn. B. carteri) are important medicinal plants widely used for their content of bioactive lipophilic triterpenes. The qualitative and quantitative determination of boswellic acids (BAs) is important for their use in dietary supplements aimed to provide a support [...] Read more.

Boswellia serrata and Boswellia sacra (syn. B. carteri) are important medicinal plants widely used for their content of bioactive lipophilic triterpenes. The qualitative and quantitative determination of boswellic acids (BAs) is important for their use in dietary supplements aimed to provide a support for osteoarthritic and inflammatory diseases. We used High Performance Liquid Chromatography (HPLC)-Diode Array Detector (DAD) coupled to ElectroSpray Ionization and tandem Mass Spectrometry (ESI-MS/MS) for the qualitative and quantitative determination of BAs extracted from the gum resins of B. sacra and B. serrata. Limit of detection (LOD), limit of quantification (LOQ), and Matrix Effect were assessed in order to validate quantitative data. Here we show that the BAs quantitative determination was 491.20 g·kg−1 d. wt (49%) in B. sacra and 295.25 g·kg−1 d. wt (30%) in B. serrata. Lower percentages of BAs content were obtained when BAs were expressed on the gum resin weight (29% and 16% for B. sacra and B. serrata, respectively). The content of Acetyl-11-Keto-β-Boswellic Acid (AKBA) was higher in B. sacra (70.81 g·kg−1 d. wt; 7%) than in B. serrata (7.35 g·kg−1 d. wt; 0.7%). Our results show that any claim of BAs content in either B. sacra or B. serrata gum resins equal to or higher than 70% or AKBA contents of 30% are simply unrealistic or based on a wrong quantitative determination. Full article

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Graphical abstract

736 KiB

Open AccessArticle

Tetranortriterpenes and Limonoids from the Roots of Aphanamixis polystachya

by Ching-Jie Lin, I-Wen Lo, Yu-Chi Lin, Shun-Ying Chen, Ching-Te Chien, Yao-Haur Kuo, Tsong-Long Hwang, Shorong-Shii Liou and Ya-Ching Shen

Molecules 2016, 21(9), 1167; https://doi.org/10.3390/molecules21091167 - 2 Sep 2016

Cited by 10 | Viewed by 5995

Abstract

Phytochemical investigation of the acetone extract from the roots of Aphanamixis polystachya resulted in isolation of four new tetranortriterpenes (1–4) in addition to one protolimonoid (methyl-1ξ,7R-diacetoxy-23R,25-dihydroxy-20S,24R-21,24-epoxy-3,4-seco-apotirucall-4(28),14(15)-diene-3-oate (5)), five known [...] Read more.

Phytochemical investigation of the acetone extract from the roots of Aphanamixis polystachya resulted in isolation of four new tetranortriterpenes (1–4) in addition to one protolimonoid (methyl-1ξ,7R-diacetoxy-23R,25-dihydroxy-20S,24R-21,24-epoxy-3,4-seco-apotirucall-4(28),14(15)-diene-3-oate (5)), five known limonoids (rohituka 3 (6), rohituka 7 (7), nymania 1 (8), rubrin G (9), prieurianin (10)) and a steroid (2,3-dihydroxy-5-pregnan-16-one (11)). Their structures were determined by spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Cytotoxic and anti-inflammatory activities of these compounds were evaluated. Compounds 4 and 5 showed significant inhibition against superoxide generation and elastase release by human neutrophils in response to (formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B) (FMLP/CB). Full article

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1730 KiB

Open AccessArticle

Triterpenes for Well-Balanced Scar Formation in Superficial Wounds

by Stefan Kindler, Matthias Schuster, Christian Seebauer, Rico Rutkowski, Anna Hauschild, Fred Podmelle, Camilla Metelmann, Bibiana Metelmann, Charlotte Müller-Debus, Hans-Robert Metelmann and Isabella Metelmann

Molecules 2016, 21(9), 1129; https://doi.org/10.3390/molecules21091129 - 27 Aug 2016

Cited by 7 | Viewed by 12214

Abstract

Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as [...] Read more.

Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as the first topical therapeutic agent with the proven clinical benefit of accelerating wound healing. Two self-conducted randomized intra-individual comparison clinical studies with a total of 220 patients involved in TBG treatment of skin graft surgical wounds have been screened for data concerning the aesthetic aspect of wound healing. Three months after surgery wound treatment with TBG resulted in about 30% of cases with more discreet scars, and standard of care in about 10%. Patients themselves appreciate the results of TBG after 3 months even more (about 50%) compared to standard of care (about 10%). One year after surgery, the superiority of TBG counts for about 25% in comparison with about 10%, and from the patients’ point of view, for 25% compared to 4% under standard of care. In the majority of wound treatment cases, there is no difference visible between TBG treatment and standard of care after 1 year of scar formation. However, in comparison, TBG still offers a better chance for discreet scars and therefore happens to be superior in good care of wounds. Full article

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1329 KiB

Open AccessArticle

Three Novel Triterpenoids from Taraxacum officinale Roots

by Takashi Kikuchi, Ayaka Tanaka, Mayu Uriuda, Takeshi Yamada and Reiko Tanaka

Molecules 2016, 21(9), 1121; https://doi.org/10.3390/molecules21091121 - 27 Aug 2016

Cited by 20 | Viewed by 6745

Abstract

Three novel lupane-, bauerane-, and euphane-type triterpenoids (1–3), in addition to seven known triterpenoids (4–10)—18β,19β-epoxy-21β-hydroxylupan-3β-yl acetate (4), 21-oxolup-18-en-3β-yl acetate (5), betulin (6), officinatrione (7), 11α-methoxyolean-12-en-3-one (8 [...] Read more.

Three novel lupane-, bauerane-, and euphane-type triterpenoids (1–3), in addition to seven known triterpenoids (4–10)—18β,19β-epoxy-21β-hydroxylupan-3β-yl acetate (4), 21-oxolup-18-en-3β-yl acetate (5), betulin (6), officinatrione (7), 11α-methoxyolean-12-en-3-one (8), eupha-7,24-dien-3-one (9), and 24-oxoeupha-7,24-dien-3β-yl acetate (10)—were isolated from the roots of Taraxacum officinale. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D-NMR spectra and electron ionization mass spectrometry (EIMS). The effects of compounds 1–10 on the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages were evaluated. Compounds 4, 6, and 10 exhibited similar NO inhibitory activities to N^G-monomethyl-l-arginine acetate (l-NMMA). These compounds did not exhibit cytotoxicity at an effective concentration. The results of present study suggest that compounds 4, 6, and 10 have potential as anti-inflammatory disease agents. Full article

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1040 KiB

Open AccessArticle

Cytotoxicity of Triterpenoid Alkaloids from Buxus microphylla against Human Tumor Cell Lines

by Shi-Tou Bai, Guo-Lei Zhu, Xing-Rong Peng, Jin-Run Dong, Mu-Yuan Yu, Jian-Chao Chen, Luo-Sheng Wan and Ming-Hua Qiu

Molecules 2016, 21(9), 1125; https://doi.org/10.3390/molecules21091125 - 26 Aug 2016

Cited by 13 | Viewed by 5743

Abstract

Three new triterpenoid alkaloids, namely buxmicrophyllines P–R (1–3), were isolated from the twigs and leaves of Buxus microphylla. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. Structurally, compounds 1–3 belong to [...] Read more.

Three new triterpenoid alkaloids, namely buxmicrophyllines P–R (1–3), were isolated from the twigs and leaves of Buxus microphylla. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. Structurally, compounds 1–3 belong to the 9,10-cycloartane type alkaloids. In addition, compound 3 exhibited moderate cytotoxic activities in vitro against HL-60, SMMC-7221, A-549, MCF-7, and SW480 cell lines (with IC₅₀ values ranging from 4.51 to 15.58 μM). Full article

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1466 KiB

Open AccessArticle

Betulin Phosphonates; Synthesis, Structure, and Cytotoxic Activity

by Elwira Chrobak, Ewa Bębenek, Monika Kadela-Tomanek, Małgorzata Latocha, Christian Jelsch, Emmanuel Wenger and Stanisław Boryczka

Molecules 2016, 21(9), 1123; https://doi.org/10.3390/molecules21091123 - 26 Aug 2016

Cited by 27 | Viewed by 7114

Abstract

Betulin derivatives are a widely studied group of compounds of natural origin due to their wide spectrum of biological activities. This paper describes new betulin derivatives, containing a phosphonate group. The allyl-vinyl isomerization and synthesis of acetylenic derivatives have been reported. Structural identification [...] Read more.

Betulin derivatives are a widely studied group of compounds of natural origin due to their wide spectrum of biological activities. This paper describes new betulin derivatives, containing a phosphonate group. The allyl-vinyl isomerization and synthesis of acetylenic derivatives have been reported. Structural identification of products as E and Z isomers has been carried out using ¹H-, ¹³C-, ³¹P-NMR, and crystallographic analysis. The crystal structure in the orthorhombic space group and analysis of crystal packing contacts for 29-diethoxyphosphoryl-28-cyclopropylpropynoyloxy-lup-20E(29)-en-3β-ol 8a are reported. All new compounds were tested in vitro for their antiproliferative activity against human T47D (breast cancer), SNB-19 (glioblastoma), and C32 (melanoma) cell lines. Full article

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Open AccessReview

Plant Resources, ¹³C-NMR Spectral Characteristic and Pharmacological Activities of Dammarane-Type Triterpenoids

by Jingya Ruan, Chang Zheng, Lu Qu, Yanxia Liu, Lifeng Han, Haiyang Yu, Yi Zhang and Tao Wang

Molecules 2016, 21(8), 1047; https://doi.org/10.3390/molecules21081047 - 12 Aug 2016

Cited by 20 | Viewed by 11526

Abstract

Dammarane-type triterpenoids (DTT) widely distribute in various medicinal plants. They have generated a great amount of interest in the field of new drug research and development. Generally, DTT are the main bioactive ingredients abundant in Araliaceae plants, such as Panax ginseng, P. [...] Read more.

Dammarane-type triterpenoids (DTT) widely distribute in various medicinal plants. They have generated a great amount of interest in the field of new drug research and development. Generally, DTT are the main bioactive ingredients abundant in Araliaceae plants, such as Panax ginseng, P. japonicas, P. notoginseng, and P. quinquefolium. Aside from Araliaceae, DTT also distribute in other families, including Betulaceae, Cucurbitaceae, Meliaceae, Rhamnaceae, and Scrophulariaceae. Until now, about 136 species belonging to 46 families have been reported to contain DTT. In this article, the genus classifications of plant sources of the botanicals that contain DTT are reviewed, with particular focus on the NMR spectral features and pharmacological activities based on literature reports, which may be benefit for the development of new drugs or food additives. Full article

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Open AccessArticle

Structures and Biogenesis of Fallaxosides D₄, D₅, D₆ and D₇, Trisulfated Non-Holostane Triterpene Glycosides from the Sea Cucumber Cucumaria fallax

by Alexandra S. Silchenko, Anatoly I. Kalinovsky, Sergey A. Avilov, Pelageya V. Andryjaschenko, Pavel S. Dmitrenok, Vladimir I. Kalinin, Ekaterina A. Chingizova, Kirill V. Minin and Valentin A. Stonik

Molecules 2016, 21(7), 939; https://doi.org/10.3390/molecules21070939 - 20 Jul 2016

Cited by 14 | Viewed by 5169

Abstract

Four new trisulfated triterpene glycosides, fallaxosides D₄ (1), D₅ (2), D₆ (3) and D₇ (4) have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida). The structures of the glycosides [...] Read more.

Four new trisulfated triterpene glycosides, fallaxosides D₄ (1), D₅ (2), D₆ (3) and D₇ (4) have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida). The structures of the glycosides have been elucidated by 2D NMR spectroscopy and HRESIMS. All the glycosides have the lanostane aglycones of a rare non-holostane type with 7(8)-, 8(9)- or 9(11)-double bonds, one or two hydroxyl groups occupying unusual positions in the polycyclic nucleus and shortened or normal side chains. The pentasaccharide carbohydrate moieties of 1–4 have three sulfate groups. The cytotoxic activity of glycosides 1–4 against the ascite form of mouse Ehrlich carcinoma cells and mouse spleen lymphocytes and hemolytic activity against mouse erythrocytes have been studied. Full article

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Open AccessArticle

Metabolism of 20(S)-Ginsenoside Rg₂ by Rat Liver Microsomes: Bioactivation to SIRT1-Activating Metabolites

by Li-Yuan Ma, Qi-Le Zhou, Xin-Bao Yang, Hong-Ping Wang and Xiu-Wei Yang

Molecules 2016, 21(6), 757; https://doi.org/10.3390/molecules21060757 - 10 Jun 2016

Cited by 20 | Viewed by 6068

Abstract

20(S)-Ginsenoside Rg₂ (1) has recently become a hot research topic due to its potent bioactivities and abundance in natural sources such as the roots, rhizomes and stems-leaves of Panax ginseng. However, due to the lack of studies [...] Read more.

20(S)-Ginsenoside Rg₂ (1) has recently become a hot research topic due to its potent bioactivities and abundance in natural sources such as the roots, rhizomes and stems-leaves of Panax ginseng. However, due to the lack of studies on systematic metabolic profiles, the prospects for new drug development of 1 are still difficult to predict, which has become a huge obstacle for its safe clinical use. To solve this problem, investigation of the metabolic profiles of 1 in rat liver microsomes was first carried out. To identify metabolites, a strategy of combined analyses based on prepared metabolites by column chromatography and ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was performed. As a result, four metabolites M1–M4, including a rare new compound named ginsenotransmetin A (M1), were isolated and the structures were confirmed by spectroscopic analyses. A series of metabolites of 1, M_A–M_G, were also tentatively identified by UPLC-Q-TOF/MS in rat liver microsomal incubate of 1. Partial metabolic pathways were proposed. Among them, 1 and its metabolites M1, M3 and M4 were discovered for the first time to be activators of SIRT1. The SIRT1 activating effects of the metabolite M1 was comparable to those of 1, while the most interesting SIRT1 activatory effects of M3 and M4 were higher than that of 1 and comparable with that of resveratrol, a positive SIRT1 activator. These results indicate that microsome-dependent metabolism may represent a bioactivation pathway for 1. This study is the first to report the metabolic profiles of 1 in vitro, and the results provide an experimental foundation to better understand the in vivo metabolic fate of 1. Full article

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Open AccessArticle

Anti-Inflammatory Oleanolic Triterpenes from Chinese Acorns

by Jie Huang, Yihai Wang, Chuan Li, Xinluan Wang and Xiangjiu He

Molecules 2016, 21(5), 669; https://doi.org/10.3390/molecules21050669 - 20 May 2016

Cited by 23 | Viewed by 6582

Abstract

Acorns play an important role in human history and are a source of food and recipes for many cultures around the world. In this study, eleven oleanolic triterpenes, one of which was novel, were isolated from Chinese acorns (Quercus serrata var. brevipetiolata). [...] Read more.

Acorns play an important role in human history and are a source of food and recipes for many cultures around the world. In this study, eleven oleanolic triterpenes, one of which was novel, were isolated from Chinese acorns (Quercus serrata var. brevipetiolata). The chemical structure of the novel triterpene, which was identified as 2α,3β,19α-trihydroxy-24-oxo-olean-12-en-28-oic acid (1), was established based on the interpretation of chemical and spectroscopic analyses, including IR, HR-ESI-MS, and NMR experiments (¹H, ¹³C NMR, DEPT, ¹H-¹H COSY, HSQC, HMBC, and NOESY). All isolated compounds were tested for their inhibitory effects on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compared with the positive control drug indomethacin (IC₅₀ = 47.4 μM), compounds 1, 3, 6 and 8 exhibited remarkable anti-inflammatory activities with IC₅₀ values of 5.4, 7.8, 4.0 and 8.9 μM, respectively. Besides, compounds 2, 4, 7 and 9 also showed moderate anti-inflammatory activities with IC₅₀ values of 10.1, 13.0, 20.1 and 17.2 μM, respectively. Furthermore, Compound 1 could inhibit TNF-α-induced IL-6 and IL-8 production in MH7A cells. Full article

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Open AccessArticle

High-Performance Liquid Chromatography with Diode Array Detector and Electrospray Ionization Ion Trap Time-of-Flight Tandem Mass Spectrometry to Evaluate Ginseng Roots and Rhizomes from Different Regions

by Hong-Ping Wang, You-Bo Zhang, Xiu-Wei Yang, Xin-Bao Yang, Wei Xu, Feng Xu, Shao-Qing Cai, Ying-Ping Wang, Yong-Hua Xu and Lian-Xue Zhang

Molecules 2016, 21(5), 603; https://doi.org/10.3390/molecules21050603 - 9 May 2016

Cited by 28 | Viewed by 7531

Abstract

Ginseng, Panax ginseng C. A. Meyer, is an industrial crop in China and Korea. The functional components in ginseng roots and rhizomes are characteristic ginsenosides. This work developed a new high-performance liquid chromatography coupled with electrospray ionization ion trap time-of-flight multistage mass spectrometry [...] Read more.

Ginseng, Panax ginseng C. A. Meyer, is an industrial crop in China and Korea. The functional components in ginseng roots and rhizomes are characteristic ginsenosides. This work developed a new high-performance liquid chromatography coupled with electrospray ionization ion trap time-of-flight multistage mass spectrometry (LC–ESI-IT-TOF-MSⁿ) method to identify the triterpenoids. Sixty compounds (1–60) including 58 triterpenoids were identified from the ginseng cultivated in China. Substances 1, 2, 7, 15–20, 35, 39, 45–47, 49, 55–57, 59, and 60 were identified for the first time. To evaluate the quality of ginseng cultivated in Northeast China, this paper developed a practical liquid chromatography–diode array detection (LC–DAD) method to simultaneously quantify 14 interesting ginsenosides in ginseng collected from 66 different producing areas for the first time. The results showed the quality of ginseng roots and rhizomes from different sources was different due to growing environment, cultivation technology, and so on. The developed LC–ESI-IT-TOF-MSⁿ method can be used to identify many more ginsenosides and the LC–DAD method can be used not only to assess the quality of ginseng, but also to optimize the cultivation conditions for the production of ginsenosides. Full article

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Open AccessArticle

Inhibition of Nitric Oxide Production in BV2 Microglial Cells by Triterpenes from Tetrapanax papyriferus

by Namki Cho, Eun Hye Moon, Hyun Woo Kim, Jaewoo Hong, John A. Beutler and Sang Hyun Sung

Molecules 2016, 21(4), 459; https://doi.org/10.3390/molecules21040459 - 7 Apr 2016

Cited by 20 | Viewed by 7054

Abstract

It is well known that activated microglia produce nitric oxide (NO), which has an important role in the pathophysiology of several neurodegenerative diseases such as Alzheimer’s disease. In the course of searching for novel therapeutic agents from medicinal plants against neuroinflammatory diseases, the [...] Read more.

It is well known that activated microglia produce nitric oxide (NO), which has an important role in the pathophysiology of several neurodegenerative diseases such as Alzheimer’s disease. In the course of searching for novel therapeutic agents from medicinal plants against neuroinflammatory diseases, the methanolic extract of Tetrapanax papyriferus was found to have significant NO inhibitory activity in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Nine oleanane-type triterpenes, including two new compounds, epipapyriogenin C-3-O-β-d-glucopyranoside (6) and 11-O-butylpapyrioside LIIc (9), were isolated from the leaves and stems of Tetrapanax papyriferus. The structures of these compounds were elucidated with 1D- and 2D-NMR and MS data. Among these Δ^11,13 oleanane-type triterpenes, compound 3 showed significant NO inhibitory activity in BV-2 cells, reducing the LPS-induced expression of COX-2 and pro-inflammatory cytokines such as TNF-α and IL-6. Compounds 7 and 9 also showed NO inhibitory activities among the Δ¹² oleanane-type triterpene saponins. These results show that oleanane-type triterpenes isolated from T. papyriferus could be a potential natural resource of NO inhibitors used in the treatment of neurodegenerative disorders. Full article

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Open AccessArticle

Optimization of Betulinic Acid Extraction from Tecomella undulata Bark Using a Box-Behnken Design and Its Densitometric Validation

by Nahida Siddiqui and Vidhu Aeri

Molecules 2016, 21(4), 393; https://doi.org/10.3390/molecules21040393 - 6 Apr 2016

Cited by 11 | Viewed by 6226

Abstract

Betulinic acid (BA) is a pentacyclic triterpenoid acid obtained from the stem bark of Tecomella undulata Seem. (Bignoniaceae). Development of an efficient extraction method for the isolation of BA is important as it has a wide range of pharmacological activity. A Box-Behnken design [...] Read more.

Betulinic acid (BA) is a pentacyclic triterpenoid acid obtained from the stem bark of Tecomella undulata Seem. (Bignoniaceae). Development of an efficient extraction method for the isolation of BA is important as it has a wide range of pharmacological activity. A Box-Behnken design (BBD) was used to investigate the effect of extraction variables such as temperature (30–60 °C), time (4–8 h) and solvent to drug ratio (300–500 mL/100 g) on the maximization of BA yield and its quantification using validated densitometric high performance thin layer chromatography coupled with ultraviolet detection (HPTLC-VIS). A quadratic polynomial model was found to best fit the model with R² = 0.99. The optimized Soxhlet extraction yielded 2.449% w/w of BA at a temperature 53.86 °C, time 6.38 h and solvent to drug ratio 371 mL/100 g. BA in Tecomella undulata bark was detected at Rf value of 0.65 at 510 nm using the solvent system toluene–ethyl acetate–glacial acetic acid (8.5:1.5:0.02 v/v/v). The analytical method was validated and the linear regression analysis reflects good linear relationship (R² = 0.9902). Lower %RSD and SEM suggested that the developed HPTLC-VIS method was precise, accurate and robust. Therefore, these economical techniques are very efficient and promising for the extraction and quantification of pharmaceutically important BA. Full article

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Open AccessArticle

Bryonolic Acid, a Triterpenoid, Protect Against N-methyl-d-Aspartate-Induced Neurotoxicity in PC12 Cells

by Jinhua Que, Miao Ye, Yuqin Zhang, Wen Xu, Huang Li, Wei Xu and Kedan Chu

Molecules 2016, 21(4), 418; https://doi.org/10.3390/molecules21040418 - 28 Mar 2016

Cited by 11 | Viewed by 5837

Abstract

Calcium overload is considered to be one of the mechanisms of cerebral ischemia. Ca²⁺ influx and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and cAMP response element-binding protein (CREB) phosphorylation are considered to be involved in N-Methyl-d-aspartate (NMDA)-induced apoptosis [...] Read more.

Calcium overload is considered to be one of the mechanisms of cerebral ischemia. Ca²⁺ influx and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and cAMP response element-binding protein (CREB) phosphorylation are considered to be involved in N-Methyl-d-aspartate (NMDA)-induced apoptosis process. This study investigated the neuroprotective effects of bryonolic acid (BA) in an NMDA-induced rat adrenal pheochromocytoma cell line (PC12) cells and the potential mechanism. PC12 was treated by NMDA to establish an excitotoxicity model. BA (110,100 and 1000 μM final concentration) was added to the medium 24 h prior to the addition of NMDA. Subsequently, a methyl thiazolyl tetrazolium (MTT) assay and a lactate dehydrogenase (LDH) release were performed. Ca²⁺ concentration was demonstrated using a scanning-dual wavelength fluorimetric method. In addition, protein and mRNA levels were determined via Western blot and real-time PCR. In the presence of BA, MTT assay and LDH assay showed that more cells were viable in comparison with the NMDA group. Moreover, the concentration of Ca²⁺ decreased with the addition of BA in culture. Furthermore, BA could upregulate protein expressions of Bcl-2, p-CREB, and p-CaMKII and downregulate protein expression of Bax. The mRNA results showed that the pattern of mRNA expression were similar to their respective protein levels. All these results indicate that BA protected PC12 cells against NMDA-induced apoptosis by inhibiting Ca²⁺ influx and regulating gene expression in the Ca²⁺-CaMKII-CREB signal pathway. Therefore, the present study supports the notion that BA may be a promising neuroprotective agent for the treatment of cerebral ischemia disease. Full article

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Open AccessArticle

Two New Oleanane-Type Saponins with Anti-Proliferative Activity from Camellia oleifera Abel. Seed Cake

by Jian-Fa Zong, Yun-Ru Peng, Guan-Hu Bao, Ru-Yan Hou and Xiao-Chun Wan

Molecules 2016, 21(2), 188; https://doi.org/10.3390/molecules21020188 - 4 Feb 2016

Cited by 26 | Viewed by 6027

Abstract

Two new oleanane-type saponins, named oleiferasaponins C₄ (1) and C₅ (2), were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galacto-pyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→2)-β- [...] Read more.

Two new oleanane-type saponins, named oleiferasaponins C₄ (1) and C₅ (2), were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galacto-pyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→2)-β-d-galactopyranosy-(1→3)]-β-d-glucopyranosid-uronic acid methyl ester (1) and 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxy-methylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2)]-[β-d-galactopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (2) through 1D- and 2D-NMR, HR-ESI-MS, and GC-MS spectroscopic methods. The two compounds exhibited potent cytotoxic activities against five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB). Full article

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Open AccessArticle

Enhancement of Cunninghamella elegans UCP/WFCC 0542 Biomass and Chitosan with Amino Acid Supply

by Ednaldo Ramos Dos Santos, Marta Cristina Freitas Da Silva, Patrícia Mendes De Souza, Antonio Cardoso Da Silva, Sergio Carvalho De Paiva, Clarissa D. C. Albuquerque, Aline E. Nascimento, Kaoru Okada and Galba M. Campos-Takaki

Molecules 2013, 18(9), 10095-10107; https://doi.org/10.3390/molecules180910095 - 22 Aug 2013

Cited by 7 | Viewed by 7276

Abstract

Studies were carried out with Cunninghamella elegans UCP/WFCC 0542 to evaluate the effects of an abundant supply of amino acids, asparagine and corn steep liquor associated with sucrose on the production of biomass and chitosan by submerged fermentation. The concentrations of the components [...] Read more.

Studies were carried out with Cunninghamella elegans UCP/WFCC 0542 to evaluate the effects of an abundant supply of amino acids, asparagine and corn steep liquor associated with sucrose on the production of biomass and chitosan by submerged fermentation. The concentrations of the components of the culture medium which were determined by a 2³ full factorial design evaluated the interactions and effects of the independent variables of the sucrose, asparagine and corn steep liquor in relation to carbon and nitrogen sources, on the production of chitosan regarding biomass. The best results were observed at the central point [asparagine 0.025%, sucrose 0.15% and 0.45% of corn steep liquor, ratio C:N=2:6], and produced maximum yields of 16.95 g/L biomass and 2.14 g/L chitosan, after 96 h of submerged fermentation. However, the lowest level of sucrose, asparagine and corn steep liquor produced a low amount of biomass (10.83 g/L) and chitosan (0.60g/L). The infrared spectrum absorption of the chitosan produced by C. elegans showed bands regarding OH-axial stretching between 3406 and 3432 cm⁻¹, superimposed on the NH stretching band with axial deformation of the amide C=O group at about 1639 cm⁻¹, NH angular deformation at approximately 1560 cm⁻¹; axial deformation of amide-CN at around 1421 cm⁻¹, symmetrical angular deformation in CH₃ at 1379 cm⁻¹, -CN axial deformation of amino groups from 1125 to 1250 cm⁻¹ and polysaccharide structure bands in the range of between 890–1150 cm⁻¹. The crystallinity index of chitosan was 60.92%, and its degree of deacetylation was 75.25%. A low percentage of a supply of sucrose and asparagine with corn steep liquor offered higher yields of biomass and chitosan production at low cost. Full article

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Open AccessReview

Triterpenoids of Marine Origin as Anti-Cancer Agents

by Yong-Xin Li, S. W. A. Himaya and Se-Kwon Kim

Molecules 2013, 18(7), 7886-7909; https://doi.org/10.3390/molecules18077886 - 4 Jul 2013

Cited by 62 | Viewed by 10398

Abstract

Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy [...] Read more.

Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy in preclinical animal models. In this review efforts have been taken to review the structural features and the potential use of triterpenoids of marine origin to be used in the pharmaceutical industry as potential anti-cancer drug leads. Full article

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Open AccessArticle

Intravenous and Subcutaneous Toxicity and Absorption Kinetics in Mice and Dogs of the Antileishmanial Triterpene Saponin PX-6518

by Louis Maes

Molecules 2013, 18(4), 4803-4815; https://doi.org/10.3390/molecules18044803 - 22 Apr 2013

Cited by 2 | Viewed by 7275

Abstract

The intravenous (IV) and subcutaneous (SC) toxicity and absorption kinetics of the antileishmanial triterpene saponin PX-6518 and its active constituents maesabalide-III and -IV were studied in mice and dogs. A high-dose wash-out study of PX-6518 at 20 mg/kg SC for 5 days and [...] Read more.

The intravenous (IV) and subcutaneous (SC) toxicity and absorption kinetics of the antileishmanial triterpene saponin PX-6518 and its active constituents maesabalide-III and -IV were studied in mice and dogs. A high-dose wash-out study of PX-6518 at 20 mg/kg SC for 5 days and a single low-dose wash-out study at 1, 2.5 or 5 mg/kg SC and IV with follow-up until day 35 after treatment were performed in mice. Beagle dogs received three escalating doses of maesabalide-III and -IV at weekly intervals (0.01, 0.1 and 0.5 mg/kg IV and maesabalide-III was also dosed SC at 0.1, 0.2 and 0.4 mg/kg). Endpoint measurements included clinical, hematological and serum biochemical parameters. Pathology and toxicokinetic studies were performed on the dogs. Whereas the neutrophils and aspartate aminotransferase and alanine aminotransferase levels were increased in the high-dose wash-out mouse study, these parameters did not change in the low-dose wash-out study. The dogs were far more susceptible than mice to liver toxicity (hepatocellular necrosis and elevated liver enzymes) and developed a painful inflammatory reaction at the SC injection site. Toxicokinetic analysis revealed a non dose-linear systemic availability with plasma concentrations above the antileishmanial IC₅₀ after only a single dose at 0.01 mg/kg IV or 0.1 mg/kg SC. Related to the long half-life (T_1/2 71–91 h after SC dosing), repeated dosing at weekly intervals may result in drug accumulation and enhanced toxicity. It was decided not to pursue further drug development for PX-6518 because of the hepatotoxic risk. Full article

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Open AccessArticle

Preparation, Purification and Regioselective Functionalization of Protoescigenin—The Main Aglycone of Escin Complex

by Mariusz M. Gruza, Kamil Jatczak, Bogdan Zagrodzki, Marta Łaszcz, Katarzyna Koziak, Maura Malińska, Piotr Cmoch, Tomasz Giller, Oliwia Zegrocka-Stendel, Krzysztof Woźniak and Grzegorz Grynkiewicz

Molecules 2013, 18(4), 4389-4402; https://doi.org/10.3390/molecules18044389 - 15 Apr 2013

Cited by 13 | Viewed by 8003

Abstract

A two-step chemical process for controlled degradation of escin, affording a mixture of olean-12-ene sapogenins, was elaborated and scaled up. The main component of the mixture—protoescigenin—was isolated and purified, in the form of its corresponding monohydrate, without resource to chromatographic methods. This material [...] Read more.

A two-step chemical process for controlled degradation of escin, affording a mixture of olean-12-ene sapogenins, was elaborated and scaled up. The main component of the mixture—protoescigenin—was isolated and purified, in the form of its corresponding monohydrate, without resource to chromatographic methods. This material was further converted into the high purity 3,24;16,22-di-O,O-isopropylidene derivative in a validated large scale laboratory process. Full article

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Open AccessArticle

Metabolomic Analysis of Methyl Jasmonate-Induced Triterpenoid Production in the Medicinal Herb Centella asiatica (L.) Urban

by Jacinda T. James, Fidele Tugizimana, Paul A. Steenkamp and Ian A. Dubery

Molecules 2013, 18(4), 4267-4281; https://doi.org/10.3390/molecules18044267 - 11 Apr 2013

Cited by 54 | Viewed by 9826

Abstract

Centella asiatica is an important source of biologically active pentacyclic triterpenoids. The enhancement of the biosynthesis of the centellosides by manipulation of associated metabolic pathways is receiving much attention. Jasmonates play critical roles in plant metabolism by up-regulating the expression of genes related [...] Read more.

Centella asiatica is an important source of biologically active pentacyclic triterpenoids. The enhancement of the biosynthesis of the centellosides by manipulation of associated metabolic pathways is receiving much attention. Jasmonates play critical roles in plant metabolism by up-regulating the expression of genes related to secondary metabolites. Here, we investigated the effect of methyl jasmonate (MeJa) in C. asiatica through targeted metabolomic profiling of asiaticoside and madecassoside as well as their aglycones, asiatic acid and madecassic acid. Cell suspensions were treated with 0.2 mM MeJa for 2, 4 and 6 days. Liquid chromatography coupled to mass spectrometry (LC-MS) was used to explore induced changes in metabolite profiles, both qualitatively and quantitatively. Principal component analysis (PCA)-derived scores plots revealed clusters of sample replicates for control and treated samples at 2, 4 and 6 days while loading plots aided in identifying signatory biomarkers (asiatic acid and madecassic acid, as well as asiaticoside and madecassoside) that clearly demonstrate the variability between samples. In addition to increased biosynthesis of the targeted centelloids, other differential changes in the intracellular metabolite profiles reflected the response of the C. asiatica cells to the MeJa-treatment as a reprogramming of the metabolome. Full article

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Open AccessArticle

Triterpene Esters: Natural Products from Dorstenia arifolia (Moraceae)

by Catharina E. Fingolo, Thabata De S. Santos, Marcelo D. M. Vianna Filho and Maria Auxiliadora C. Kaplan

Molecules 2013, 18(4), 4247-4256; https://doi.org/10.3390/molecules18044247 - 11 Apr 2013

Cited by 49 | Viewed by 8715

Abstract

The phytochemical study of Dorstenia arifolia Lam. (Moraceae) has led to the identification of 18 triterpenes esterified by fatty acids, five triterpenes without esterification, 12 triterpenes esterified by acetic acid, together with a known furanocoumarin: α-amyrin (1), β-amyrin (2) [...] Read more.

The phytochemical study of Dorstenia arifolia Lam. (Moraceae) has led to the identification of 18 triterpenes esterified by fatty acids, five triterpenes without esterification, 12 triterpenes esterified by acetic acid, together with a known furanocoumarin: α-amyrin (1), β-amyrin (2) α-amyrin acetate (3) β-amyrin acetate (4), α-amyrin octanoate (5), β-amyrin octanoate (6), α-amyrin decanoate (7), β-amyrin decanoate (8), α-amyrin dodecanoate (9), β-amyrin dodecanoate (10), α-amyrin tetradecanoate (11), β-amyrin tetradecanoate (12), α-amyrin hexadecanoate (13), β-amyrin hexadecanoate (14), glutinol (15), glutinyl acetate (16), 11-oxo-α-amyrin (17), 11-oxo-β-amyrin (18), 11-oxo-α-amyrin acetate (19), 11-oxo-β-amyrin acetate (20) 11-oxo-α-amyrin octanoate (21) 11-oxo-β-amyrin octanoate (22), 11-oxo-α-amyrin decanoate (23), 11-oxo-β-amyrin decanoate (24) 11-oxo-α-amyrin dodecanoate (25) 11-oxo-β-amyrin dodecanoate (26), ursa-9(11),12-dien-3-yl acetate (27), oleana-9(11),12-dien-3-yl acetate (28), ursa-9(11),12-dien-3-yl decanoate (29), oleana-9(11),12-dien-3-yl decanoate (30), 12,13-epoxyolean-3-yl acetate (31), 12,13-epoxyolean-9(11)en-3-yl acetate (32), taraxeryl acetate (33), lupenyl acetate (34), lanosta-8,24-dien-3-yl acetate (35) and psoralen (36). The identification of the triterpene compounds isolated as isomeric mixtures obtained from the hexane extract was based mainly in mass spectra and ¹³C-NMR data. The long-chain alkanoic acid esters of the triterpenes α- and β-amyrin; 11-oxo-α- and 11-oxo-β-amyrin; ursa- and olean-9(11),12-dien-3-yl; have not been reported before in the literature as constituents of the Dorstenia genus. Full article

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Open AccessReview

Protostane and Fusidane Triterpenes: A Mini-Review

by Ming Zhao, Tanja Gödecke, Jordan Gunn, Jin-Ao Duan and Chun-Tao Che

Molecules 2013, 18(4), 4054-4080; https://doi.org/10.3390/molecules18044054 - 5 Apr 2013

Cited by 70 | Viewed by 12030

Abstract

Protostane triterpenes belong to a group of tetracyclic triterpene that exhibit unique structural characteristics. Their natural distribution is primarily limited to the genus Alisma of the Alismataceae family, but they have also been occasionally found in other plant genera such as Lobelia, [...] Read more.

Protostane triterpenes belong to a group of tetracyclic triterpene that exhibit unique structural characteristics. Their natural distribution is primarily limited to the genus Alisma of the Alismataceae family, but they have also been occasionally found in other plant genera such as Lobelia, Garcinia, and Leucas. To date, there are 59 known protostane structures. Many of them have been reported to possess biological properties such as improving lipotropism, hepatoprotection, anti-viral activity against hepatitis B and HIV-I virus, anti-cancer activity, as well as reversal of multidrug resistance in cancer cells. On the other hand, fusidanes are fungal products characterized by 29-nor protostane structures. They possess antibiotic properties against staphylococci, including the methicillin-resistant Staphylococcus aureus (MRSA). Fusidic acid is a representative member which has found clinical applications. This review covers plant sources of the protostanes, their structure elucidation, characteristic structural and spectral properties, as well as biological activities. The fungal sources, structural features, biological activities of fusidanes are also covered in this review. Additionally, the biogenesis of these two types of triterpenes is discussed and a refined pathway is proposed. Full article

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Open AccessReview

Steroidal Triterpenes of Cholesterol Synthesis

by Jure Ačimovič and Damjana Rozman

Molecules 2013, 18(4), 4002-4017; https://doi.org/10.3390/molecules18044002 - 4 Apr 2013

Cited by 54 | Viewed by 11774

Abstract

Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that leads to cholesterol, an essential structural component of mammalian cell membranes, required for proper membrane permeability and fluidity. The last part of the pathway involves steroidal triterpenes with cholestane ring structures. It starts [...] Read more.

Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that leads to cholesterol, an essential structural component of mammalian cell membranes, required for proper membrane permeability and fluidity. The last part of the pathway involves steroidal triterpenes with cholestane ring structures. It starts by conversion of acyclic squalene into lanosterol, the first sterol intermediate of the pathway, followed by production of 20 structurally very similar steroidal triterpene molecules in over 11 complex enzyme reactions. Due to the structural similarities of sterol intermediates and the broad substrate specificity of the enzymes involved (especially sterol-Δ²⁴-reductase; DHCR24) the exact sequence of the reactions between lanosterol and cholesterol remains undefined. This article reviews all hitherto known structures of post-squalene steroidal triterpenes of cholesterol synthesis, their biological roles and the enzymes responsible for their synthesis. Furthermore, it summarises kinetic parameters of enzymes (V_max and K_m) and sterol intermediate concentrations from various tissues. Due to the complexity of the post-squalene cholesterol synthesis pathway, future studies will require a comprehensive meta-analysis of the pathway to elucidate the exact reaction sequence in different tissues, physiological or disease conditions. A major reason for the standstill of detailed late cholesterol synthesis research was the lack of several steroidal triterpene standards. We aid to this efforts by summarizing commercial and laboratory standards, referring also to chemical syntheses of meiosis-activating sterols. Full article

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Open AccessCommunication

Anti-Inflammatory Cycloartane-Type Saponins of Astragalus membranaceus

by Dae-Young Lee, Hyung-Jun Noh, Jehun Choi, Kyeong-Hee Lee, Min-Ho Lee, Ji-Hyun Lee, Yoonpyo Hong, Seung-Eun Lee, Seung-Yu Kim and Geum-Soog Kim

Molecules 2013, 18(4), 3725-3732; https://doi.org/10.3390/molecules18043725 - 25 Mar 2013

Cited by 64 | Viewed by 9971

Abstract

A new cycloartane-type triterpene glycoside, agroastragaloside V (1) was isolated from the roots of Astragalus membranaceus. The structure was identified as 3-O-β-(2'-O-acetyl)-D-xylopyranosyl-6-O-β-D-glucopyranosyl-(24S)-3β,6α,24α,25-tetrahydroxy- [...] Read more.

A new cycloartane-type triterpene glycoside, agroastragaloside V (1) was isolated from the roots of Astragalus membranaceus. The structure was identified as 3-O-β-(2'-O-acetyl)-D-xylopyranosyl-6-O-β-D-glucopyranosyl-(24S)-3β,6α,24α,25-tetrahydroxy- 9,19-cyclolanostane, by means of spectroscopic methods, including HR-FAB/MS, 1D NMR (¹H, ¹³C, DEPT), 2D NMR (gCOSY, gHSQC, gHMBC, NOESY), and IR spectroscopy. Four known cycloartane glycosides, namely, agroastragaloside I (2), agroastragaloside II (3), isoastragaloside II (4) and astragaloside IV (5) were also isolated. All isolated compounds were tested for the ability to inhibit LPS-induced nitric oxide production in RAW264.7 macrophages. Full article

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Open AccessArticle

Efficient Synthesis and Anti-Fungal Activity of Oleanolic Acid Oxime Esters

by Hanqing Zhao, Minjie Zhou, Lifeng Duan, Wei Wang, Jianjun Zhang, Daoquan Wang and Xiaomei Liang

Molecules 2013, 18(3), 3615-3629; https://doi.org/10.3390/molecules18033615 - 21 Mar 2013

Cited by 52 | Viewed by 8205

Abstract

In order to develop potential glucosamine-6-phosphate synthase inhibitors and anti-fungal agents, twenty five oleanolic acid oxime esters were synthesized in an efficient way. The structures of the new compounds were confirmed by MS, HRMS, ¹H-NMR and ¹³C-NMR. Preliminary studies based on [...] Read more.

In order to develop potential glucosamine-6-phosphate synthase inhibitors and anti-fungal agents, twenty five oleanolic acid oxime esters were synthesized in an efficient way. The structures of the new compounds were confirmed by MS, HRMS, ¹H-NMR and ¹³C-NMR. Preliminary studies based on means of the Elson-Morgan method indicated that many compounds exhibited some inhibitory activity of glucosamine-6-phosphate synthase (GlmS), and the original fungicidal activities results showed that some of the compounds exhibited good fungicidal activities towards Sclerotinia sclerotiorum (Lib.) de Bary, Rhizoctonia solani Kuhn and Botrytis cinerea Pers at the concentration of 50 µg/mL. These compounds would thus merit further study and development as antifungal agents. Full article

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Open AccessArticle

Inhibition of Telomerase Activity by Oleanane Triterpenoid CDDO-Me in Pancreatic Cancer Cells is ROS-Dependent

by Dorrah Deeb, Xiaohua Gao, Yongbo Liu, Nadimpalli R. S. Varma, Ali S. Arbab and Subhash C. Gautam

Molecules 2013, 18(3), 3250-3265; https://doi.org/10.3390/molecules18033250 - 13 Mar 2013

Cited by 43 | Viewed by 8144

Abstract

Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a synthetic derivative of oleanolic acid, a triterpene, with apoptosis-inducing activity in a wide range of cancer cells. Induction of apoptosis by CDDO-Me is associated with the generation of reactive oxygen species (ROS) and inhibition of telomerase activity. In the [...] Read more.

Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a synthetic derivative of oleanolic acid, a triterpene, with apoptosis-inducing activity in a wide range of cancer cells. Induction of apoptosis by CDDO-Me is associated with the generation of reactive oxygen species (ROS) and inhibition of telomerase activity. In the present study, we investigated the role of ROS in inhibition of telomerase by CDDO-me. Treatment of MiaPaCa-2 and Panc-1 pancreatic cancer cell lines with CDDO-Me induced the production of hydrogen peroxide and superoxide anions and inhibited the telomerase activity. Pretreatment of cells with N-acetylcycsteine, a general purpose antioxidant or overexpression of glutathione peroxidase (GPx) or superoxide dismutase-1 (SOD-1) blocked the telomerase inhibitory activity of CDDO-Me. Furthermore, blocking ROS generation also prevented the inhibition of hTERT gene expression, hTERT protein production and expression of a number of hTERT–regulatory proteins by CDDO-Me (e.g., c-Myc, Sp1, NF-κB and p-Akt). Data also showed that Akt plays an important role in the activation of telomerase activity. Together, these data suggest that inhibition of telomerase activity by CDDO-Me is mediated through a ROS-dependent mechanism; however, more work is needed to fully understand the role of ROS in down-regulation of hTERT gene and hTERT-regulatory proteins by CDDO-Me. Full article

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Open AccessArticle

Repeated Oral Administration of Oleanolic Acid Produces Cholestatic Liver Injury in Mice

by Yuan-Fu Lu, Xiao-Li Wan, Yasha Xu and Jie Liu

Molecules 2013, 18(3), 3060-3071; https://doi.org/10.3390/molecules18033060 - 7 Mar 2013

Cited by 51 | Viewed by 8471

Abstract

Oleanolic acid (OA) is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 [...] Read more.

Oleanolic acid (OA) is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 mg/kg), po for 10 days, and the hepatotoxicity was determined by serum biochemistry, histopathology, and toxicity-related gene expression via real-time RT-PCR. Animal body weight loss was evident at OA doses of 1,000 µmol/kg and above. Serum alanine aminotransferase activities were increased in a dose-dependent manner, indicative of hepatotoxicity. Serum total bilirubin concentrations were increased, indicative of cholestasis. OA administration produced dose-dependent pathological lesions to the liver, including inflammation, hepatocellular apoptosis, necrosis, and feathery degeneration indicative of cholestasis. These lesions were evident at OA doses of 500 µmol/kg and above. Real-time RT-PCR revealed that OA produced dose-dependent increases in acute phase proteins (MT-1, Ho-1, Nrf2 and Nqo1), decreases in bile acid synthesis genes (Cyp7a1 and Cyp8b1), and decreases in liver bile acid transporters (Ntcp, Bsep, Oatp1a1, Oatp1b2, and Ostβ). Thus, the clinical use of OA and OA-type triterpenoids should balance the beneficial effects and toxicity potentials. Full article

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Open AccessArticle

Simultaneous Determination of Flavonoids, Isochlorogenic Acids and Triterpenoids in Ilex hainanensis Using High Performance Liquid Chromatography Coupled with Diode Array and Evaporative Light Scattering Detection

by Bo Peng, Chun-Feng Qiao, Jing Zhao, Wei-Hua Huang, De-Jun Hu, Hua-Gang Liu and Shao-Ping Li

Molecules 2013, 18(3), 2934-2941; https://doi.org/10.3390/molecules18032934 - 4 Mar 2013

Cited by 10 | Viewed by 7584

Abstract

A high performance liquid chromatography coupled with diode array and evaporative light scattering detection (HPLC-DAD-ELSD) method for simultaneous determination of eight major bioactive compounds including two flavonoids (rutin and eriodictyol-7-O-β-D-glucopyranoside), two isochlorogenic acids (isochlorogenic acid A and isochlorogenic acid C) and [...] Read more.

A high performance liquid chromatography coupled with diode array and evaporative light scattering detection (HPLC-DAD-ELSD) method for simultaneous determination of eight major bioactive compounds including two flavonoids (rutin and eriodictyol-7-O-β-D-glucopyranoside), two isochlorogenic acids (isochlorogenic acid A and isochlorogenic acid C) and four triterpenoids (ilexhainanoside D, ilexsaponin A₁, ilexgenin A and ursolic acid) in Ilex hainanensis has been developed for the first time. The 283 nm wavelength was chosen for determination of two flavonoids and two isochlorogenic acids. ELSD was applied to determine four triterpenoids. The analysis was performed on an Agilent Zorbax SB-C₁₈ column (250 × 4.6 mm i.d., 5 µm) with gradient elution of 0.2% formic acid in water and acetonitrile. The method was validated for linearity, limit of detection, limit of quantification, precision, repeatability and accuracy. The proposed method has been successfully applied for simultaneous quantification of the analytes in four samples of Ilex hainanensis, which is helpful for quality control of this plant. Full article

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Open AccessArticle

Cell Suspension Culture of Eriobotrya japonica Regulates the Diabetic and Hyperlipidemic Signs of High-Fat-Fed Mice

by Chun-Ching Shih, Jiun-Lin Ciou, Cheng-Hsiu Lin, Jin-Bin Wu and Hui-Ya Ho

Molecules 2013, 18(3), 2726-2753; https://doi.org/10.3390/molecules18032726 - 1 Mar 2013

Cited by 39 | Viewed by 14689

Abstract

The present study investigates the anti-hyperlipidemic and antihyperglycemic effects and mechanism in high-fat (HF)-fed mice of cell suspension culture of Eriobotrya japonica (TA), which contains a great number of pentacyclic terpenoids. Firstly, C57BL/6J mice were randomly divided into two groups: the control (CON) [...] Read more.

The present study investigates the anti-hyperlipidemic and antihyperglycemic effects and mechanism in high-fat (HF)-fed mice of cell suspension culture of Eriobotrya japonica (TA), which contains a great number of pentacyclic terpenoids. Firstly, C57BL/6J mice were randomly divided into two groups: the control (CON) group was fed with a low-fat diet (n = 9), whereas the experimental group was fed a 45% HF diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and was orally given TA or rosiglitazone or not for 4 weeks. Blood and visceral adipose tissue, liver tissue and skeletal muscle were examined. Treatment with TA reduced body weight gain, weights of white adipose tissue (WAT) (including epididymal, perirenal, mesenteric WAT and visceral fat), and hepatic triacylglycerol content significantly without affecting food intake in diet-induced diabetic mice. TA effectively prevented HF diet-induced increases in the levels of blood glucose, insulin, leptin and HOMA-IR index (p < 0.001, p < 0.05, p < 0.05, p < 0.01, respectively) and attenuated insulin resistance. Treatment with TA, adipocytes in the visceral depots showed a reduction in size. TA effectively significantly increased the protein contents of phosphorylation of AMPK-α (Thr172) both in liver and adipose tissue. It is shown that TA exhibits hypolipidemic effect in HF-fed mice by decreasing gene expressions of fatty acid synthesis, including acyl-coenzyme A: diacylglycerol acyltransferase (DGAT) 2, which catalyzes the final step in the synthesis of triglycerides, and antidiabetic properties occurred as a result of decreased hepatic glucose production via phosphenolpyruvate carboxykinase (PEPCK) down- regulation, improved insulin sensitization and TA (at 1.0 g/kg dose) decreased expression of hepatic and adipose 11-β-hydroxysteroid dehydroxygenase (11β-HSD1) gene, which contributed in attenuating diabetic state. Futhermore, TA at doses of 0.5 and 1.0 g/kg had serum lipid-lowering action characterized by the inhibition of DGAT 1 expression. Thus, amelioration of diabetic and dyslipidemic state by TA in HF-fed mice occurred by regulation of PEPCK, DGAT2 and AMPK phosphorylation. Full article

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Open AccessArticle

Ulososides and Urabosides — Triterpenoid Saponins from the Caribbean Marine Sponge Ectyoplasia ferox

by Jhonny Colorado, Diana Muñoz, Diana Marquez, Maria Elena Marquez, Juan Lopez, Olivier P. Thomas and Alejandro Martinez

Molecules 2013, 18(3), 2598-2610; https://doi.org/10.3390/molecules18032598 - 27 Feb 2013

Cited by 14 | Viewed by 9184

Abstract

Three new triterpene glycosides, named ulososide F (1), urabosides A (2) and B (3), together with the previously reported ulososide A (4), were isolated from the Caribbean marine sponge Ectyoplasia ferox. Their structures were [...] Read more.

Three new triterpene glycosides, named ulososide F (1), urabosides A (2) and B (3), together with the previously reported ulososide A (4), were isolated from the Caribbean marine sponge Ectyoplasia ferox. Their structures were elucidated using extensive interpretation of 1D and 2D-NMR data, as well as HRESIMS. The aglycon of all compounds is a rare 30-norlonastane and the sugar residues were identified after acid hydrolysis and GC analyses. Cytotoxicities of the isolated compounds were evaluated against Jurkat and CHO cell lines by a MTT in vitro assay as well as a hemolysis assay. Unexpectedly, all these saponin derivatives showed very low activity in our bioassays. Full article

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Open AccessArticle

Hirtinone, a Novel Cycloartane-Type Triterpene and Other Compounds from Trichilia hirta L. (Meliaceae)

by Ivo José Curcino Vieira, Otoniel De Aquino Azevedo, Jucimar Jorgeane De Souza, Raimundo Braz-Filho, Milena Dos Santos Gonçalves and Marcelo Francisco De Araújo

Molecules 2013, 18(3), 2589-2597; https://doi.org/10.3390/molecules18032589 - 26 Feb 2013

Cited by 18 | Viewed by 8091

Abstract

One novel triterpene cycloartane-type, named hirtinone (1), six protolimonoids – nilocitin (2), dihydronilocitin B (3), melianone epimers (4) and (5), piscidinol A (6) and melianone lactone (7), one tertranortriterpenoid, [...] Read more.

One novel triterpene cycloartane-type, named hirtinone (1), six protolimonoids – nilocitin (2), dihydronilocitin B (3), melianone epimers (4) and (5), piscidinol A (6) and melianone lactone (7), one tertranortriterpenoid, hirtin (8), and one sesquiterpene, spathulenol (9), were identified in the fruits of Trichilia hirta. The structures were established by 1D and 2D NMR (¹H and ¹³C-NMR, DEPTQ, ¹H-¹H-COSY, ¹H-¹H-NOESY, HSQC and HMBC), high resolution mass spectroscopy (HR-ESI-MS) and infrared (IR) spectral data. Full article

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Open AccessArticle

Methyl Antcinate A Suppresses the Population of Cancer Stem-Like Cells in MCF7 Human Breast Cancer Cell Line

by Chih-Yu Peng, Pin-Chung Fong, Cheng-Chia Yu, Wan-Chi Tsai, Yew-Min Tzeng and Wen-Wei Chang

Molecules 2013, 18(3), 2539-2548; https://doi.org/10.3390/molecules18032539 - 26 Feb 2013

Cited by 20 | Viewed by 9292

Abstract

Methyl antcinate A (MAA) is an ergostane-type triterpenoid extracted from the fruiting bodies of Antrodia camphorate that has been reported to be a cytotoxic agent towards some types of cancer cells, such as oral cancer and liver cancer. Cancer stem cells (CSCs) are [...] Read more.

Methyl antcinate A (MAA) is an ergostane-type triterpenoid extracted from the fruiting bodies of Antrodia camphorate that has been reported to be a cytotoxic agent towards some types of cancer cells, such as oral cancer and liver cancer. Cancer stem cells (CSCs) are a particular population within cancer cells which are responsible for tumor initiation, drug resistance and metastasis and targeting CSCs is an emerging area in cancer therapy. In this study, we examine the effect of MAA on cancer stem-like cells in the MCF7 human breast cancer cell line. Although MAA displayed very low cytotoxic effect towards MCF7 under normal culture conditions, it did show good inhibitory effects on the self-renewal capability which was examined by mammosphere culture including primary and secondary sphere. MAA also inhibited cell migration ability of MCF7 sphere cells. By western blot analysis, MAA was shown to suppress the expression of heat shock protein 27 and increase the expression of IkBα and p53. In conclusion, our data demonstrate that MAA has anti-CSC activity and is worthy of future development of potent anticancer agents. Full article

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Open AccessArticle

Cytotoxic and Radical Scavenging Nor-Dammarane Triterpenoids from Viburnum mongolicum

by Xiaohua Wang and Wei Wang

Molecules 2013, 18(2), 1405-1417; https://doi.org/10.3390/molecules18021405 - 24 Jan 2013

Cited by 7 | Viewed by 4987

Abstract

The ethanol extract of the whole plants of Viburnum mongolicum afforded six new nor-dammarane triterpenoids: 3β,12β-dihydroxy-25,26,27-trinordammara-22-en -24,20-olide (1), 3β,12β-dihydroxy-24α-methoxy-25,26,27-trinordammara-20,24-epoxy (2), 3β-O-acetyl-12β-hydroxy-23,24,25,26,27-hexanordammarane-20-one (3 [...] Read more.

The ethanol extract of the whole plants of Viburnum mongolicum afforded six new nor-dammarane triterpenoids: 3β,12β-dihydroxy-25,26,27-trinordammara-22-en -24,20-olide (1), 3β,12β-dihydroxy-24α-methoxy-25,26,27-trinordammara-20,24-epoxy (2), 3β-O-acetyl-12β-hydroxy-23,24,25,26,27-hexanordammarane-20-one (3), 12β-O- acetyl-15α-hydroxy-17β-methoxy-3-oxo-20,21,22-23,24,25,26,27-octanordammanrane (4), 12β-O-acetyl-15α,17β-dihydroxy-3-oxo-20,21,22-23,24,25,26,27-octanordammanrane (5), and 12β,15α-dihydroxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanordammanrane (6), together with two known nor-dammarane triterpenoids, 12β-hydroxy-3-oxo-24α-methoxy- 25,26,27-trinordammara-20,24-epoxy (7) and 3β,12β-dihydroxy-23,24,25,26,27- hexanordammarane-20-one (8). The structures of the isolated compounds were established based on 1D and 2D (¹H-¹H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic potential against seven tumor cell lines and radical scavenging activities. Compounds 4–6 exhibited significant cytotoxic activities against all tested tumor cell lines and radical scavenging activities against ABTS^·+ radicals comparable with the standard drug Trolox. Full article

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Open AccessArticle

A New Triterpenoid from Teucrium viscidum

by Xincai Hao, Jinwen Zhang, Guangxin Xia, Yongbo Xue, Zengwei Luo, Yanyan Si, Guangmin Yao and Yonghui Zhang

Molecules 2013, 18(1), 1262-1269; https://doi.org/10.3390/molecules18011262 - 21 Jan 2013

Cited by 13 | Viewed by 6127

Abstract

A new ursane-type triterpenoid, 3β-hydroxy-urs-30-p-Z-hydroxycinnamoyloxy-12-en-28-oic-acid (1), together with three known triterpenoids, 3β-hydroxy-urs-30-p-E-hydroxycinnamoyloxy-12-en-28-oic-acid (2), 2α,3β,19α-trihydroxy-urs-12-en-28-oic-acid (3), and ursolic acid ( [...] Read more.

A new ursane-type triterpenoid, 3β-hydroxy-urs-30-p-Z-hydroxycinnamoyloxy-12-en-28-oic-acid (1), together with three known triterpenoids, 3β-hydroxy-urs-30-p-E-hydroxycinnamoyloxy-12-en-28-oic-acid (2), 2α,3β,19α-trihydroxy-urs-12-en-28-oic-acid (3), and ursolic acid (4), four known lignans, pinoresinol (5), 9α-hydroxypinoresinol (6), (+)-medioresinol (7), and (+)-kobusin (8), and two steroids, β-sitosterol (9), and daucosterol (10), were isolated from the whole parts of Teucrium viscidum. Their structures were established by a combination of spectroscopic data analysis, besides comparison with literature data. Compounds 1–4 were evaluated for their inhibitory activities against 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). Full article

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Open AccessArticle

Antiprotozoal Activity of Quinonemethide Triterpenes from Maytenus ilicifolia (Celastraceae)

by Vania A. F. F. M. Dos Santos, Karoline M. Leite, Mariana Da Costa Siqueira, Luis O. Regasini, Isabel Martinez, Camila T. Nogueira, Mariana Kolos Galuppo, Beatriz S. Stolf, Ana Maria Soares Pereira, Regina M. B. Cicarelli, Maysa Furlan and Marcia A. S. Graminha

Molecules 2013, 18(1), 1053-1062; https://doi.org/10.3390/molecules18011053 - 15 Jan 2013

Cited by 52 | Viewed by 7880

Abstract

The present study describes the leishmanicidal and trypanocidal activities of two quinonemethide triterpenes, maytenin (1) and pristimerin (2), isolated from Maytenus ilicifolia root barks (Celastraceae). The compounds were effective against the Trypanosomatidae Leishmania amazonensis and Leishmania chagasi and Trypanosoma [...] Read more.

The present study describes the leishmanicidal and trypanocidal activities of two quinonemethide triterpenes, maytenin (1) and pristimerin (2), isolated from Maytenus ilicifolia root barks (Celastraceae). The compounds were effective against the Trypanosomatidae Leishmania amazonensis and Leishmania chagasi and Trypanosoma cruzi, etiologic agents of leishmaniasis and Chagas’ disease, respectively. The quinonemethide triterpenes 1 and 2 exhibited a marked in vitro leishmanicidal activity against promastigotes and amastigotes with 50% inhibitory concentration (IC₅₀) values of less than 0.88 nM. Both compounds showed IC₅₀ lower than 0.3 nM against Trypanosoma cruzi epimastigotes. The selectivity indexes (SI) based on BALB/c macrophages for L. amazonensis and L. chagasi were 243.65 and 46.61 for (1) and 193.63 and 23.85 for (2) indicating that both compounds presented high selectivity for Leishmania sp. The data here presented suggests that these compounds should be considered in the development of new and more potent drugs for the treatment of leishmaniasis and Chagas’ disease. Full article

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2012

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Open AccessArticle

Telomerase Reverse Transcriptase (TERT) is a Therapeutic Target of Oleanane Triterpenoid CDDO-Me in Prostate Cancer

by Yongbo Liu, Xiaohua Gao, Dorrah Deeb, Ali S. Arbab and Subhash C. Gautam

Molecules 2012, 17(12), 14795-14809; https://doi.org/10.3390/molecules171214795 - 11 Dec 2012

Cited by 20 | Viewed by 5585

Abstract

Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is an synthetic oleanane triterpenoid with strong antiprolifertive and proapoptotic activities in cancer cells. However, the effect of CDDO-Me on human telomerase reverse transcriptase (hTERT) and its telomerase activity in prostate cancer cells has not been studied. We investigated the role [...] Read more.

Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is an synthetic oleanane triterpenoid with strong antiprolifertive and proapoptotic activities in cancer cells. However, the effect of CDDO-Me on human telomerase reverse transcriptase (hTERT) and its telomerase activity in prostate cancer cells has not been studied. We investigated the role of hTERT in mediating the anticancer activity of CDDO-Me in prostate cancer cells in vitro and in vivo. The inhibition of cell proliferation and induction of apoptosis by CDDO-Me in LNCaP and PC-3 prostate cancer cell lines was associated with the inhibition of hTERT gene expression, hTERT telomerase activity and a number of proteins that regulate hTERT transcriptionally and post-translationally. Furthermore, ablation of hTERT protein increased the sensitivity of cancer cells to CDDO-Me, whereas its overexpression rendered them resistant to CDDO-Me. In addition, inhibition of progression of preneoplastic lesions (i.e., low and high-grade prostate intraepithelial neoplasms, PINs) to adenocarcinoma of the prostate by CDDO-Me in TRAMP mice was associated with significant decrease in TERT and its regulatory proteins in the prostate gland. These data provide evidence that telomerase is a potential target of CDDO-Me for the prevention and treatment of prostate cancer. Full article

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Open AccessArticle

New Triterpenes from Maytenus robusta: Structural Elucidation Based on NMR Experimental Data and Theoretical Calculations

by Grasiely F. Sousa, Lucienir P. Duarte, Antônio F. C. Alcântara, Grácia D. F. Silva, Sidney A. Vieira-Filho, Roqueline R. Silva, Djalma M. Oliveira and Jacqueline A. Takahashi

Molecules 2012, 17(11), 13439-13456; https://doi.org/10.3390/molecules171113439 - 12 Nov 2012

Cited by 74 | Viewed by 9252

Abstract

Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide ( [...] Read more.

Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide (8), 3β-hydroxy-21β-H-hop-22(29)-ene (9), 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (10), 3,4-seco-friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract of M. robusta leaves. Compounds 8 and 9 are described herein for the first time. The structure and stereochemistry of both compounds were experimentally established by IR, HRLC-MS, and 1D (¹H, ¹³C, and DEPT 135) and 2D (HSQC, HMBC and COSY) NMR data and supported by correlations with carbon chemical shifts calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also described for the first time, and their chemical structures were established by comparison with NMR data of similar structures described in the literature and correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a mixture of 11 and sitosterol, and 3β,11β-dihydroxyfriedelane (4) were evaluated by the Ellman’s method and all these compounds showed acethylcholinesterase inhibitory properties. Full article

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Open AccessCommunication

Bioactive Oleanane, Lupane and Ursane Triterpene Acid Derivatives

by Maria De L. e Silva, Juceni P. David, Lidércia C. R. C. Silva, Rauldenis A. F. Santos, Jorge M. David, Luciano S. Lima, Pedro S. Reis and Renato Fontana

Molecules 2012, 17(10), 12197-12205; https://doi.org/10.3390/molecules171012197 - 17 Oct 2012

Cited by 53 | Viewed by 10489

Abstract

Betulinic, ursolic and oleanolic acids isolated from the aerial parts of Eriope blanchetii (Lamiaceae) were subjected to different esterification reactions, yielding 12 C-3 position ester derivatives. All compounds were identified using spectroscopic techniques, such as IR, ¹H-NMR and MS. The derivatives were [...] Read more.

Betulinic, ursolic and oleanolic acids isolated from the aerial parts of Eriope blanchetii (Lamiaceae) were subjected to different esterification reactions, yielding 12 C-3 position ester derivatives. All compounds were identified using spectroscopic techniques, such as IR, ¹H-NMR and MS. The derivatives were further investigated for their antioxidant level, Artemia salina lethality and antimicrobial activity. Full article

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Open AccessArticle

A New Saponin from Tea Seed Pomace (Camellia oleifera Abel) and Its Protective Effect on PC12 Cells

by Xin-Fu Zhang, Ying-Ying Han, Guan-Hu Bao, Tie-Jun Ling, Liang Zhang, Li-Ping Gao and Tao Xia

Molecules 2012, 17(10), 11721-11728; https://doi.org/10.3390/molecules171011721 - 1 Oct 2012

Cited by 45 | Viewed by 8862

Abstract

A new triterpenoid saponin, oleiferasaponin A₁, was isolated from tea seed pomace (Camellia oleifera Abel). The structure of oleiferasaponin A₁ was elucidated on the basis of chemical and physicochemical evidence and was found to be 22-O-cis [...] Read more.

A new triterpenoid saponin, oleiferasaponin A₁, was isolated from tea seed pomace (Camellia oleifera Abel). The structure of oleiferasaponin A₁ was elucidated on the basis of chemical and physicochemical evidence and was found to be 22-O-cis-2-hexenoyl-A₁-barrigenol 3-O-[β-D-galactopyranosyl(1→2)] [β-D-glucopyranosyl(1→2)-α-L-arabinopyranosyl(1→3)]-β-D-glucopyranosiduronic acid. PC12 cells injured with H₂O₂ were used as the model to test the protective effects of oleiferasaponin A₁. The results indicated that oleiferasaponin A₁ can potentially prevent the H₂O₂-induced cell death of PC12 cells. Full article

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Open AccessArticle

Phorbol Esters from Jatropha Meal Triggered Apoptosis, Activated PKC-δ, Caspase-3 Proteins and Down-Regulated the Proto-Oncogenes in MCF-7 and HeLa Cancer Cell Lines

by Ehsan Oskoueian, Norhani Abdullah and Syahida Ahmad

Molecules 2012, 17(9), 10816-10830; https://doi.org/10.3390/molecules170910816 - 10 Sep 2012

Cited by 26 | Viewed by 6935

Abstract

Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia contains phorbol esters (PEs). The potential benefits of PEs present in the meal as anticancer agent are still not well understood. Hence, this study was conducted to evaluate the cytotoxic [...] Read more.

Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia contains phorbol esters (PEs). The potential benefits of PEs present in the meal as anticancer agent are still not well understood. Hence, this study was conducted to evaluate the cytotoxic effects and mode of actions of PEs isolated from Jatropha meal against breast (MCF-7) and cervical (HeLa) cancer cell lines. Isolated PEs inhibited cells proliferation in a dose-dependent manner of both MCF-7 and HeLa cell lines with the IC₅₀ of 128.6 ± 2.51 and 133.0 ± 1.96 µg PMA equivalents/mL respectively, while the values for the phorbol 12-myristate 13-acetate (PMA) as positive control were 114.7 ± 1.73 and 119.6 ± 3.73 µg/mL, respectively. Microscopic examination showed significant morphological changes that resemble apoptosis in both cell lines when treated with PEs and PMA at IC₅₀ concentration after 24 h. Flow cytometry analysis and DNA fragmentation results confirmed the apoptosis induction of PEs and PMA in both cell lines. The PEs isolated from Jatropha meal activated the PKC-δ and down-regulated the proto-oncogenes (c-Myc, c-Fos and c-Jun). These changes probably led to the activation of Caspase-3 protein and apoptosis cell death occurred in MCF-7 and HeLa cell lines upon 24 h treatment with PEs and PMA. Phorbol esters of Jatropha meal were found to be promising as an alternative to replace the chemotherapeutic drugs for cancer therapy. Full article

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2009

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1064 KiB

Open AccessReview

Steroidal Triterpenes: Design of Substrate-Based Inhibitors of Ergosterol and Sitosterol Synthesis

by Jialin Liu and William David Nes

Molecules 2009, 14(11), 4690-4706; https://doi.org/10.3390/molecules14114690 - 18 Nov 2009

Cited by 27 | Viewed by 20012

Abstract

This article reviews the design and study, in our own laboratory and others, of new steroidal triterpenes with a modified lanosterol or cycloartenol frame. These compounds, along with a number of known analogs with the cholestane skeleton, have been evaluated as reversible or [...] Read more.

This article reviews the design and study, in our own laboratory and others, of new steroidal triterpenes with a modified lanosterol or cycloartenol frame. These compounds, along with a number of known analogs with the cholestane skeleton, have been evaluated as reversible or irreversible inhibitors of sterol C24-methyltransferase (SMT) from plants, fungi and protozoa. The SMT catalyzes the C24-methylation reaction involved with the introduction of the C24-methyl group of ergosterol and the C24-ethyl group of sitosterol, cholesterol surrogates that function as essential membrane inserts in many photosynthetic and non-photosynthetic eukaryotic organisms. Sterol side chains constructed with a nitrogen, sulfur, bromine or fluorine atom, altered to possess a methylene cyclopropane group, or elongated to include terminal double or triple bonds are shown to exhibit different in vitro activities toward the SMT which are mirrored in the inhibition potencies detected in the growth response of treated cultured human and plant cells or microbes. Several of the substrate-based analogs surveyed here appear to be taxaspecific compounds acting as mechanism-based inactivators of the SMT, a crucial enzyme not synthesized by animals. Possible mechanisms for the inactivation process and generation of novel products catalyzed by the variant SMTs are discussed. Full article

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Open AccessReview

Pentacyclic Triterpenoids from the Medicinal Herb, Centella asiatica (L.) Urban

by Jacinda T. James and Ian A. Dubery

Molecules 2009, 14(10), 3922-3941; https://doi.org/10.3390/molecules14103922 - 9 Oct 2009

Cited by 306 | Viewed by 34922

Abstract

Centella asiatica accumulates large quantities of pentacyclic triterpenoid saponins, collectively known as centelloids. These terpenoids include asiaticoside, centelloside, madecassoside, brahmoside, brahminoside, thankuniside, sceffoleoside, centellose, asiatic-, brahmic-, centellic- and madecassic acids. The triterpene saponins are common secondary plant metabolites and are synthesized via the [...] Read more.

Centella asiatica accumulates large quantities of pentacyclic triterpenoid saponins, collectively known as centelloids. These terpenoids include asiaticoside, centelloside, madecassoside, brahmoside, brahminoside, thankuniside, sceffoleoside, centellose, asiatic-, brahmic-, centellic- and madecassic acids. The triterpene saponins are common secondary plant metabolites and are synthesized via the isoprenoid pathway to produce a hydrophobic triterpenoid structure (aglycone) containing a hydrophilic sugar chain (glycone). The biological activity of saponins has been attributed to these characteristics. In planta, the Centella triterpenoids can be regarded as phytoanticipins due to their antimicrobial activities and protective role against attempted pathogen infections. Preparations of C. asiatica are used in traditional and alternative medicine due to the wide spectrum of pharmacological activities associated with these secondary metabolites. Here, the biosynthesis of the centelloid triterpenoids is reviewed; the range of metabolites found in C. asiatica, together with their known biological activities and the chemotype variation in the production of these metabolites due to growth conditions are summarized. These plant-derived pharmacologically active compounds have complex structures, making chemical synthesis an economically uncompetitive option. Production of secondary metabolites by cultured cells provides a particularly important benefit to manipulate and improve the production of desired compounds; thus biotechnological approaches to increase the concentrations of the metabolites are discussed. Full article

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Open AccessReview

Squalene Emulsions for Parenteral Vaccine and Drug Delivery

by Christopher B. Fox

Molecules 2009, 14(9), 3286-3312; https://doi.org/10.3390/molecules14093286 - 1 Sep 2009

Cited by 171 | Viewed by 23003

Abstract

Squalene is a linear triterpene that is extensively utilized as a principal component of parenteral emulsions for drug and vaccine delivery. In this review, the chemical structure and sources of squalene are presented. Moreover, the physicochemical and biological properties of squalene-containing emulsions are [...] Read more.

Squalene is a linear triterpene that is extensively utilized as a principal component of parenteral emulsions for drug and vaccine delivery. In this review, the chemical structure and sources of squalene are presented. Moreover, the physicochemical and biological properties of squalene-containing emulsions are evaluated in the context of parenteral formulations. Historical and current parenteral emulsion products containing squalene or squalane are discussed. The safety of squalene-based products is also addressed. Finally, analytica techniques for characterization of squalene emulsions are examined. Full article

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564 KiB

Open AccessReview

Chemical and Biological Characterization of Oleanane Triterpenoids from Soy

by Wei Zhang and David G. Popovich

Molecules 2009, 14(8), 2959-2975; https://doi.org/10.3390/molecules14082959 - 10 Aug 2009

Cited by 72 | Viewed by 20042

Abstract

Soyasaponins are a group of complex and structural diverse oleanane triterpenoids found in soy (Glycine max) and other legumes. They are primarily classified into two main groups − group A and B − based on the attachment of sugar moieties at [...] Read more.

Soyasaponins are a group of complex and structural diverse oleanane triterpenoids found in soy (Glycine max) and other legumes. They are primarily classified into two main groups − group A and B − based on the attachment of sugar moieties at positions C-3 and C-22 of the ring structures. Group A soyasaponins are bidesmosidic, while group B soyasaponins are monodesmosidic. Group B soyasaponins are further classified into two subcategories known as 2,3-dihydro-2,5-dihydroxy-6 -methyl-4H-pyran-4-one (DDMP) and non-DDMP conjugated molecules. The preparation and purification of soyasaponin molecules is complicated by the presence of bioactive soy isoflavones, which often overlap with soyasaponin in polarity and must removed from extracts before biological assessment. Soyasaponin extracts, aglycones of group A and B and individual group B soyasaponins such as soyasaponin I have been reported to posses specific bioactive properties, such as in vitro anti-cancer properties by modulating the cell cycle and inducing apoptosis. The isolation, chemical characterization and detection strategies by HPLC and HPLC-MS are reviewed, along with the reported bioactive effects of soyasaponin extracts and individual molecules in cultured cancer cell experiments. Full article

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Open AccessReview

Steroidal Lactones from Withania somnifera, an Ancient Plant for Novel Medicine

by Mohammad Hossein Mirjalili, Elisabeth Moyano, Mercedes Bonfill, Rosa M. Cusido and Javier Palazón

Molecules 2009, 14(7), 2373-2393; https://doi.org/10.3390/molecules14072373 - 3 Jul 2009

Cited by 456 | Viewed by 66291

Abstract

Withania somnifera, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. In view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. The [...] Read more.

Withania somnifera, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. In view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. The major chemical constituents of the Withania genus, the withanolides, are a group of naturally occurring C28-steroidal lactone triterpenoids built on an intact or rearranged ergostane framework, in which C-22 and C-26 are appropriately oxidized to form a six-membered lactone ring. In recent years, numerous pharmacological investigations have been carried out into the components of W. somnifera extracts. We present here an overview of the chemical structures of triterpenoid components and their biological activity, focusing on two novel activities, tumor inhibition and antiangiogenic properties of withaferin A and the effects of withanolide A on Alzheimer's disease. The most recent attempts in biotechnological production of withanolides are also discussed. Full article

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Open AccessArticle

Pentacyclic Triterpene Distribution in Various Plants – Rich Sources for a New Group of Multi-Potent Plant Extracts

by Sebastian Jäger, Holger Trojan, Thomas Kopp, Melanie N. Laszczyk and Armin Scheffler

Molecules 2009, 14(6), 2016-2031; https://doi.org/10.3390/molecules14062016 - 4 Jun 2009

Cited by 519 | Viewed by 31572

Abstract

Pentacyclic triterpenes are secondary plant metabolites widespread in fruit peel, leaves and stem bark. In particular the lupane-, oleanane-, and ursane triterpenes display various pharmacological effects while being devoid of prominent toxicity. Therefore, these triterpenes are promising leading compounds for the development of [...] Read more.

Pentacyclic triterpenes are secondary plant metabolites widespread in fruit peel, leaves and stem bark. In particular the lupane-, oleanane-, and ursane triterpenes display various pharmacological effects while being devoid of prominent toxicity. Therefore, these triterpenes are promising leading compounds for the development of new multi-targeting bioactive agents. Screening of 39 plant materials identified triterpene rich (> 0.1% dry matter) plant parts. Plant materials with high triterpene concentrations were then used to obtain dry extracts by accelerated solvent extraction resulting in a triterpene content of 50 - 90%. Depending on the plant material, betulin (birch bark), betulinic acid (plane bark), oleanolic acid (olive leaves, olive pomace, mistletoe sprouts, clove flowers), ursolic acid (apple pomace) or an equal mixture of the three triterpene acids (rosemary leaves) are the main components of these dry extracts. They are quantitatively characterised plant extracts supplying a high concentration of actives and therefore can be used for development of phytopharmaceutical formulations. Full article

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Open AccessArticle

Comparision of the Cytotoxic Effects of Birch Bark Extract, Betulin and Betulinic Acid Towards Human Gastric Carcinoma and Pancreatic Carcinoma Drug-sensitive and Drug-Resistant Cell Lines

by Marcin Drag, Pawel Surowiak, Malgorzata Drag-Zalesinska, Manfred Dietel, Hermann Lage and Józef Oleksyszyn

Molecules 2009, 14(4), 1639-1651; https://doi.org/10.3390/molecules14041639 - 24 Apr 2009

Cited by 73 | Viewed by 18558

Abstract

Betulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicity towards a number of cancer cell lines. These compounds can be found in the bark of the many plants. In this report we have compared the cytotoxic activity of crude birch bark [...] Read more.

Betulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicity towards a number of cancer cell lines. These compounds can be found in the bark of the many plants. In this report we have compared the cytotoxic activity of crude birch bark extract and purified betulin and betulinic acid towards human gastric carcinoma (EPG85-257) and human pancreatic carcinoma (EPP85-181) drug-sensitive and drug-resistant (daunorubicin and mitoxantrone) cell lines. Our results show significant differences in sensitivity between cell lines depending on the compound used, and suggest that both betulin and betulinic acid can be considered as a promising leads in the treatment of cancer. Full article

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Open AccessCommunication

Stereochemistry of 16a-Hydroxyfriedelin and 3-Oxo-16-methylfriedel-16-ene Established by 2D NMR Spectroscopy

by Lucienir Pains Duarte, Roqueline Rodrigues Silva de Miranda, Salomão Bento Vasconcelos Rodrigues Rodrigues, Grácia Divina De Fátima Silva, Sidney Augusto Vieira Filho and Vagner Fernandes Knupp

Molecules 2009, 14(2), 598-607; https://doi.org/10.3390/molecules14020598 - 4 Feb 2009

Cited by 11 | Viewed by 14270

Abstract

Friedelin (1), 3b-friedelinol (2), 28-hydroxyfriedelin (3), 16a-hydroxyfriedelin (4), 30-hydroxyfriedelin (5) and 16a,28-dihydroxyfriedelin (6) were isolated through fractionation of the hexane extract obtained from branches of Salacia elliptica. After a week in CDCl₃ solution, 16a-hydroxyfriedelin (4) reacted turning into 3-oxo-16-methylfriedel-16-ene (7). This is [...] Read more.

Friedelin (1), 3b-friedelinol (2), 28-hydroxyfriedelin (3), 16a-hydroxyfriedelin (4), 30-hydroxyfriedelin (5) and 16a,28-dihydroxyfriedelin (6) were isolated through fractionation of the hexane extract obtained from branches of Salacia elliptica. After a week in CDCl₃ solution, 16a-hydroxyfriedelin (4) reacted turning into 3-oxo-16-methylfriedel-16-ene (7). This is the first report of a dehydration followed by a Nametkin rearrangement of a pentacyclic triterpene in CDCl₃ solution occurring in the NMR tube. These seven pentacyclic triterpenes was identified through NMR spectroscopy and the stereochemistry of compound 4 and 7 was established by 2D NMR (NOESY) spectroscopy and mass spectrometry (GC-MS). It is also the first time that all the ¹³C-NMR and 2D NMR spectral data are reported for compounds 4 and 7. Full article

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Open AccessReview

Biological and Pharmacological Activities of Squalene and Related Compounds: Potential Uses in Cosmetic Dermatology

by Zih-Rou Huang, Yin-Ku Lin and Jia-You Fang

Molecules 2009, 14(1), 540-554; https://doi.org/10.3390/molecules14010540 - 23 Jan 2009

Cited by 357 | Viewed by 53871

Abstract

Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with [...] Read more.

Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with reasonable amounts found in olive oil, palm oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene, the main component of skin surface polyunsaturated lipids, shows some advantages for the skin as an emollient and antioxidant, and for hydration and its antitumor activities. It is also used as a material in topically applied vehicles such as lipid emulsions and nanostructured lipid carriers (NLCs). Substances related to squalene, including β-carotene, coenzyme Q10 (ubiquinone) and vitamins A, E, and K, are also included in this review article to introduce their benefits to skin physiology. We summarize investigations performed in previous reports from both in vitro and in vivo models. Full article

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2008

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282 KiB

Open AccessArticle

A Preliminary Pharmacokinetic Study of Betulin, the Main Pentacyclic Triterpene from Extract of Outer Bark of Birch (Betulae alba cortex)

by Sebastian Jäger, Melanie N. Laszczyk and Armin Scheffler

Molecules 2008, 13(12), 3224-3235; https://doi.org/10.3390/molecules13123224 - 18 Dec 2008

Cited by 124 | Viewed by 19063

Abstract

During the last two decades triterpenes have attracted attention because of their pharmacological potential. Triterpene extract (TE) from outer bark of birch consisting mainly of betulin is able to form an oleogel which was successfully tested in the treatment of actinic keratosis. Some [...] Read more.

During the last two decades triterpenes have attracted attention because of their pharmacological potential. Triterpene extract (TE) from outer bark of birch consisting mainly of betulin is able to form an oleogel which was successfully tested in the treatment of actinic keratosis. Some aspects of TE in vitro pharmacology are already known. Now we show preliminary pharmacokinetics of betulin and results of a subchronic toxicity study of TE in rats and dogs. Because of poor aqueous solubility of the TE-triterpenes (< 0.1 μg/mL respectively), for pharmacokinetic studies it was suspended in sesame oil (rats, i.p.) and PEG 400 / 0.9 % NaCl (dogs, s.c.). I.p. administered, betulin, the main component of TE, shows time dependency over a period of 4 h and reaches a dose-independent serum level of 0.13 μg/mL. Dose dependency was observed with s.c. administration. At 300 mg/kg a maximum plasma concentration of 0.33 μg/mL betulin was detected after 28 daily applications. The subchronic toxicity study showed no toxicity of TE in rats (i.p.) and dogs (s.c.). In conclusion, triterpene extract from birch bark is safe, its betulin is bioavailable and in addition to published triterpene biological activities TE provides high potential for further pharmaceutical and pharmacological research. Full article

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Open AccessArticle

Bioactive Pentacyclic Triterpenes from the Stems of Combretum laxum

by Eder Bisoli, Walmir Silva Garcez, Lidilhone Hamerski, Caroline Tieppo and Fernanda Rodrigues Garcez

Molecules 2008, 13(11), 2717-2728; https://doi.org/10.3390/molecules13112717 - 1 Nov 2008

Cited by 91 | Viewed by 16236

Abstract

Two new triterpene glucosides, β-D-glucopyranosyl 2α,3β,24-trihydroxyolean- 12-en-28-oate and β-D-glucopyranosyl 2α,3β,23,24-tetrahydroxyurs-12-en-28-oate, in addition to nine known compounds belonging to three different triterpene classes (oleanane-, ursane- and lupane-type) have been isolated from the stems of a specimen of Combretum laxum growing in the “Pantanal” of [...] Read more.

Two new triterpene glucosides, β-D-glucopyranosyl 2α,3β,24-trihydroxyolean- 12-en-28-oate and β-D-glucopyranosyl 2α,3β,23,24-tetrahydroxyurs-12-en-28-oate, in addition to nine known compounds belonging to three different triterpene classes (oleanane-, ursane- and lupane-type) have been isolated from the stems of a specimen of Combretum laxum growing in the “Pantanal” of the central-western region of Brazil. Among the known triterpenes, β-D-glucopyranosyl 2α,3β,6β-trihydroxyolean-12-en-28-oate is reported for the first time in the Combretaceae, while bellericoside and asiatic acid are described for the first time in the genus Combretum. The structures of the isolated compounds have been established on the basis of spectral techniques (1D-, 2D-NMR and MS). Their in vitro antifungal activities against standard strains of Candida albicans, C. krusei and Cryptococcus neoformans were also evaluated in this work. Full article

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