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1776 KiB

Open AccessArticle

Constituents of the Roots of Dichapetalum pallidum and Their Anti-Proliferative Activity

by Dorcas Osei-Safo, Godwin Akpeko Dziwornu, Regina Appiah-Opong, Mary Anti Chama, Isaac Tuffour, Reiner Waibel, Richard Amewu and Ivan Addae-Mensah

Molecules 2017, 22(4), 532; https://doi.org/10.3390/molecules22040532 - 27 Mar 2017

Cited by 13 | Viewed by 4477

Abstract

As part of our search for bioactive compounds from the Dichapetalaceae, repeated chromatographic purification of the roots of a hitherto unexamined species, Dichapetalum pallidum, led to the isolation of the newly occurring 7-hydroxydichapetalin P (1) and the known dichapetalins A [...] Read more.

As part of our search for bioactive compounds from the Dichapetalaceae, repeated chromatographic purification of the roots of a hitherto unexamined species, Dichapetalum pallidum, led to the isolation of the newly occurring 7-hydroxydichapetalin P (1) and the known dichapetalins A (2) and X (3). Also isolated were the known compounds friedelin-2,3-lactone (4), friedelan-3-one (6), friedelan-3β-ol (7) and pomolic (8), as well as the dipeptide aurantiamide acetate (5). The compounds were characterized by direct interpretation of their IR, 1D NMR and 2D NMR spectral data and by comparison of their physico-chemical data, including their chromatographic profiles, with the literature and authentic samples in our compound library for the genus Dichapetalum. The compounds were assayed for their anti-proliferative activities against the human T-lymphocytic leukemia (Jurkat), acute promyelocytic leukemia (HL-60) and T-lymphoblast-like leukemia (CEM) cell lines. Overall, dichapetalin X showed the strongest (3.14 μM) and broadest cytotoxic activities against all the leukemic cell lines tested, exhibiting even stronger activities than the standard compound, curcumin. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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1773 KiB

Open AccessArticle

Isolation, Characterization and Antiproliferative Activity of New Metabolites from the South African Endemic Red Algal Species Laurencia alfredensis

by Godwin A. Dziwornu, Mino R. Caira, Jo-Anne de la Mare, Adrienne L. Edkins, John J. Bolton, Denzil R. Beukes and Suthananda N. Sunassee

Molecules 2017, 22(4), 513; https://doi.org/10.3390/molecules22040513 - 23 Mar 2017

Cited by 18 | Viewed by 5878

Abstract

The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis. [...] Read more.

The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis. A sequence of column chromatography, preparative TLC and normal phase HPLC resulted in the isolation of eleven compounds comprising three labdane-type diterpenes (1–3), four polyether triterpenes (4–7), three cholestane-type ecdysteroids (8–10) and a glycolipid (11). Compounds 1–3, 5–8 and 10 have not previously been reported, while compound 9 is reported here for the first time from a natural source and the known compound 11 isolated for the first time from the genus Laurencia. The structural elucidation and the relative configuration assignments of the compounds were accomplished by extensive use of 1D- and 2D-NMR, HR-ESI-MS, UV and IR spectroscopic techniques, while the absolute configuration of compound 1 was determined by single-crystal X-ray diffraction analysis. All compounds were evaluated against the MDA-MB-231 breast and HeLa cervical cancer cell lines. Compound 2 exhibited low micromolar antiproliferative activity (IC₅₀ = 9.3 µM) against the triple negative breast carcinoma and compound 7 was similarly active (IC₅₀ = 8.8 µM) against the cervical cancer cell line. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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3163 KiB

Open AccessArticle

Facilitated Visual Interpretation of Scores in Principal Component Analysis by Bioactivity-Labeling of 1H-NMR Spectra—Metabolomics Investigation and Identification of a New α-Glucosidase Inhibitor in Radix Astragali

by Yueqiu Liu, Nils T. Nyberg, Anna K. Jäger and Dan Staerk

Molecules 2017, 22(3), 411; https://doi.org/10.3390/molecules22030411 - 6 Mar 2017

Cited by 13 | Viewed by 5367

Abstract

Radix Astragali is a component of several traditional medicines used for the treatment of type 2 diabetes in China. Radix Astragali is known to contain isoflavones, which inhibit α-glucosidase in the small intestines, and thus lowers the blood glucose levels. In this study, [...] Read more.

Radix Astragali is a component of several traditional medicines used for the treatment of type 2 diabetes in China. Radix Astragali is known to contain isoflavones, which inhibit α-glucosidase in the small intestines, and thus lowers the blood glucose levels. In this study, 21 samples obtained from different regions of China were extracted with ethyl acetate, then the IC50-values were determined, and the crude extracts were analyzed by 1H-NMR spectroscopy. A principal component analysis of the 1H-NMR spectra labeled with their IC50-values, that is, bioactivity-labeled 1H-NMR spectra, showed a clear correlation between spectral profiles and the α-glucosidase inhibitory activity. The loading plot and LC-HRMS/NMR of microfractions indicated that previously unknown long chain ferulates could be partly responsible for the observed antidiabetic activity of Radix Astragali. Subsequent preparative scale isolation revealed a compound not previously reported, linoleyl ferulate (1), showing α-glucosidase inhibitory activity (IC50 0.5 mM) at a level comparable to the previously studied isoflavones. A closely related analogue, hexadecyl ferulate (2), did not show significant inhibitory activity, and the double bonds in the alcohol part of 1 seem to be important structural features for the α-glucosidase inhibitory activity. This proof of concept study demonstrates that bioactivity-labeling of the 1H-NMR spectral data of crude extracts allows global and nonselective identification of individual constituents contributing to the crude extract’s bioactivity. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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1393 KiB

Open AccessArticle

Screening of Peruvian Medicinal Plants for Tyrosinase Inhibitory Properties: Identification of Tyrosinase Inhibitors in Hypericum laricifolium Juss

by Yanymee Nimesia Guillen Quispe, Seung Hwan Hwang, Zhiqiang Wang and Soon Sung Lim

Molecules 2017, 22(3), 402; https://doi.org/10.3390/molecules22030402 - 4 Mar 2017

Cited by 39 | Viewed by 8760

Abstract

Tyrosinase inhibitors are of far-ranging importance in cosmetics, medicinal products, and food industries. Peru is a diverse country with a wide variety of plants that may contain excellent anti-tyrosinase inhibitors. In the present study, the tyrosinase inhibitory properties of 50 medicinal plant extracts [...] Read more.

Tyrosinase inhibitors are of far-ranging importance in cosmetics, medicinal products, and food industries. Peru is a diverse country with a wide variety of plants that may contain excellent anti-tyrosinase inhibitors. In the present study, the tyrosinase inhibitory properties of 50 medicinal plant extracts from Peru were investigated using tyrosinase assay. Among plant extracts, those that showed an inhibition rate >50% were Hypericum laricifolium Juss., Taraxacum officinaleF.H.Wigg., and Muehlenbeckia vulcanicaMeisn., with H. laricifolium Juss. showing the greatest anti-tyrosinase activity. Although H. laricifolium Juss. has been widely used as a medicinal plant by Peruvians, little is known regarding its bioactive components and effects on tyrosinase activity. For this reason, we attempted to discover tyrosinase inhibitors in H. laricifolium Juss. for the first time. The bioactive components were separated by Sephadex LH-20 chromatography and eluted with 100% methanol. Eight compounds were discovered and characterized by high-performance liquid chromatography coupled with diode array detection (HPLC-DAD): protocatechuic acid, p-hydroxybenzoic acid, chlorogenic acid, vanilic acid, caffeic acid, kaempferol 3-O-glucuronide, quercetin, and kaempferol. In addition, the concentration of these compounds required for 50% inhibition (IC₅₀) of tyrosinase activity were evaluated. Quercetin exhibited the strongest tyrosinase inhibition (IC₅₀ 14.29 ± 0.3 μM). Therefore, the Peruvian plant H. laricifolium Juss. could be a novel source for anti-tyrosinase activity. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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3502 KiB

Open AccessArticle

ZYZ-772 Prevents Cardiomyocyte Injury by Suppressing Nox4-Derived ROS Production and Apoptosis

by Ying Wang, Liangjie Zhong, Xinhua Liu and Yi Zhun Zhu

Molecules 2017, 22(2), 331; https://doi.org/10.3390/molecules22020331 - 21 Feb 2017

Cited by 21 | Viewed by 7342

Abstract

Nox-dependent signaling plays critical roles in the development of heart failure, cardiac hypertrophy, and myocardial infarction. NADPH oxidase 4 (Nox4) as a major source of oxidative stress in the heart offers a new therapeutic target in cardiovascular disease. In the present work, a [...] Read more.

Nox-dependent signaling plays critical roles in the development of heart failure, cardiac hypertrophy, and myocardial infarction. NADPH oxidase 4 (Nox4) as a major source of oxidative stress in the heart offers a new therapeutic target in cardiovascular disease. In the present work, a novel flavonoid was isolated from Zanthoxylum bungeanum. Its structure was elucidated as Quercetin-3-O-(6′′-O-α-l-rhamnopyransoyl)-β-d-glucopyranoside-7-O-β-d-glucopyranoside (ZYZ-772) for the first time. ZYZ-772 exhibited significant cardio-protective property against CoCl₂ induced H9c2 cardiomyocyte cells injury. In CoCl₂ stimulated cardiomyocyte injury, ZYZ-772 inhibited expression of Nox4, and alleviated ROS overproduction. Importantly, ROS triggered MAPKs phosphorylation and P53 signaling mediated apoptosis were restored by ZYZ-772. Our findings present the first piece of evidence for the therapeutic properties of ZYZ-772 in preventing cardiomyocyte injury, which could be attributed to the suppression of Nox4/MAPKs/P53 axis. This will offer a novel therapeutic strategy for the treatment of cardiac ischemia disease. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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680 KiB

Open AccessCommunication

Production and Anti-Melanoma Activity of Methoxyisoflavones from the Biotransformation of Genistein by Two Recombinant Escherichia coli Strains

by Chien-Min Chiang, Yu-Jhe Chang, Jiumn-Yih Wu and Te-Sheng Chang

Molecules 2017, 22(1), 87; https://doi.org/10.3390/molecules22010087 - 4 Jan 2017

Cited by 18 | Viewed by 5508

Abstract

Biotransformation of the soy isoflavone genistein by sequential 3′-hydroxylation using recombinant Escherichia coli expressing tyrosinase from Bacillus megaterium and then methylation using another recombinant E. coli expressing O-methyltransferase from Streptomyces peucetius was conducted. The results showed that two metabolites were produced from [...] Read more.

Biotransformation of the soy isoflavone genistein by sequential 3′-hydroxylation using recombinant Escherichia coli expressing tyrosinase from Bacillus megaterium and then methylation using another recombinant E. coli expressing O-methyltransferase from Streptomyces peucetius was conducted. The results showed that two metabolites were produced from the biotransformation, identified as 5,7,4′-trihydroxy-3′-methoxyisoflavone and 5,7,3′-trihydroxy-4′-methoxyisoflavone, respectively, based on their mass and nuclear magnetic resonance spectral data. 5,7,4′-Trihydroxy-3′-methoxyisoflavone showed potent antiproliferative activity toward mouse B16 melanoma cells with an IC₅₀ value of 68.8 μM. In contrast, the compound did not show any cytotoxicity toward mouse normal fibroblast cells, even at 350 μM concentration. The results of the present study offer insight on the production of both 5,7,4′-trihydroxy-3′-methoxyisoflavone and 5,7,3′-trihydroxy-4′-methoxyisoflavone by two recombinant E. coli strains and the potential anti-melanoma applications of 5,7,4′-trihydroxy-3′-methoxyisoflavone. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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1500 KiB

Open AccessArticle

Pharmacological Properties of Riparin IV in Models of Pain and Inflammation

by Olívia Azevêdo Nascimento, Renan Fernandes do Espírito-Santo, Luíza Carolina França Opretzka, José Maria Barbosa-Filho, Stanley Juan Chavez Gutierrez, Cristiane Flora Villarreal and Milena Botelho Pereira Soares

Molecules 2016, 21(12), 1757; https://doi.org/10.3390/molecules21121757 - 21 Dec 2016

Cited by 20 | Viewed by 5551

Abstract

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory [...] Read more.

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory mediators were measured by radioimmunoassay and Real-Time PCR. Riparins I, II, III and IV (1.56–100 mg/kg; ip) produced dose-related antinociceptive effects in the formalin test, exhibiting ED₅₀ values of 22.93, 114.2, 31.05 and 6.63 mg/kg, respectively. Taking the greater potency as steering parameter, riparin IV was further investigated. Riparin IV did not produce antinociceptive effect on the tail flick, suggesting that its antinociception is not a centrally-mediated action. In fact, riparin IV (1.56–25 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on the complete Freund’s adjuvant (CFA)-induced paw inflammation in mice. During CFA-induced inflammation, riparin IV did not modulate either the production of cytokines, TNF-α and IL-10, or COX-2 mRNA expression. On the other hand, riparin IV decreased the PGE₂ levels in the inflamed paw. In in vitro assays, riparin IV did not exhibit suppressive activities in activated macrophages. These results indicate, for the first time, that riparin IV induces antinociceptive and anti-inflammatory effects, possibly through the inhibition of prostanoid production. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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7885 KiB

Open AccessArticle

Inhibition of Hypoxia-Induced Retinal Angiogenesis by Specnuezhenide, an Effective Constituent of Ligustrum lucidum Ait., through Suppression of the HIF-1α/VEGF Signaling Pathway

by Jianming Wu, Xiao Ke, Wei Fu, Xiaoping Gao, Hongcheng Zhang, Wei Wang, Na Ma, Manxi Zhao, Xiaofeng Hao and Zhirong Zhang

Molecules 2016, 21(12), 1756; https://doi.org/10.3390/molecules21121756 - 21 Dec 2016

Cited by 42 | Viewed by 7669

Abstract

Specnuezhenide (SPN), one of the main ingredients of Chinese medicine “Nü-zhen-zi”, has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion [...] Read more.

Specnuezhenide (SPN), one of the main ingredients of Chinese medicine “Nü-zhen-zi”, has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion model of human acute retinal pigment epithelial-19 (ARPE-19) cells by exposure of 150 μM CoCl₂ to the cells and determined the VEGFA concentrations, the mRNA expressions of VEGFA, hypoxia inducible factor-1α (HIF-1α) & prolyl hydroxylases 2 (PHD-2), and the protein expressions of HIF-1α and PHD-2 after treatment of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1, 1.0 μg/mL) or SPN (0.2, 1.0 and 5.0 μg/mL). Furthermore, rat pups with retinopathy were treated with SPN (5.0 and 10.0 mg/kg) in an 80% oxygen atmosphere and the retinal avascular areas were assessed through visualization using infusion of ADPase and H&E stains. The results showed that SPN inhibited VEGFA secretion by ARPE-19 cells under hypoxia condition, down-regulated the mRNA expressions of VEGFA and PHD-2 slightly, and the protein expressions of VEGFA, HIF-1α and PHD-2 significantly in vitro. SPN also prevented hypoxia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy in vivo. These results indicate that SPN ameliorates retinal neovascularization through inhibition of HIF-1α/VEGF signaling pathway. Therefore, SPN has the potential to be developed as an agent for the prevention and treatment of diabetic retinopathy. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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389 KiB

Open AccessArticle

Antimalarial Activity of the Chemical Constituents of the Leaf Latex of Aloe pulcherrima Gilbert and Sebsebe

by Tekleab Teka, Daniel Bisrat, Mariamawit Yonathan Yeshak and Kaleab Asres

Molecules 2016, 21(11), 1415; https://doi.org/10.3390/molecules21111415 - 28 Oct 2016

Cited by 24 | Viewed by 5043

Abstract

Malaria is one of the three major global public health threats due to a wide spread resistance of the parasites to the standard antimalarial drugs. Considering this growing problem, the ethnomedicinal approach in the search for new antimalarial drugs from plant sources has [...] Read more.

Malaria is one of the three major global public health threats due to a wide spread resistance of the parasites to the standard antimalarial drugs. Considering this growing problem, the ethnomedicinal approach in the search for new antimalarial drugs from plant sources has proven to be more effective and inexpensive. The leaves of Aloe pulcherrima Gilbert and Sebsebe, an endemic Ethiopian plant, are locally used for the treatment of malaria and other infectious diseases. Application of the leaf latex of A. pulcherrima on preparative silica gel TLC led to the isolation of two C-glycosylated anthrones, identified as nataloin (1) and 7-hydroxyaloin (2) by spectroscopic techniques (UV, IR, ¹H- and ¹³C-NMR, HR-ESIMS). Both the latex and isolated compounds displayed antimalarial activity in a dose-independent manner using a four-day suppressive test, with the highest percent suppression of 56.2% achieved at 200 mg/kg/day for 2. The results indicate that both the leaf latex of A. pulcherrima and its two major constituents are endowed with antiplasmodial activities, which support the traditional use of the leaves of the plant for the treatment of malaria. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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