Pharmaceutics

Editorial

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4 pages, 217 KiB

Open AccessEditorial

Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications

by Maria Camilla Bergonzi, Charles M. Heard and Javier Garcia-Pardo

Pharmaceutics 2022, 14(10), 2116; https://doi.org/10.3390/pharmaceutics14102116 - 5 Oct 2022

Cited by 9 | Viewed by 1689

Abstract

The plant kingdom is one of the richest sources of bioactive compounds with pharmaceutical potential [...] Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

Research

Jump to: Editorial, Review

25 pages, 3854 KiB

Open AccessArticle

Eugenia sulcata (Myrtaceae) Nanoemulsion Enhances the Inhibitory Activity of the Essential Oil on P2X7R and Inflammatory Response In Vivo

by Bettina Quintanilha Magalhães, Francisco P. Machado, Paola S. Sanches, Bárbara Lima, Deborah Quintanilha Falcão, Natalia von Ranke, Murilo Lamim Bello, Carlos Rangel Rodrigues, Marcelo Guerra Santos, Leandro Rocha and Robson X. Faria

Pharmaceutics 2022, 14(5), 911; https://doi.org/10.3390/pharmaceutics14050911 - 21 Apr 2022

Cited by 11 | Viewed by 2414

Abstract

P2X7R is a purinergic receptor with broad expression throughout the body, especially in immune system cells. P2X7R activation causes inflammatory mediators to release, including interleukin-1β (IL-1β), the processing and release of which are critically dependent on this ion channel activation. P2X7R’s therapeutic potential [...] Read more.

P2X7R is a purinergic receptor with broad expression throughout the body, especially in immune system cells. P2X7R activation causes inflammatory mediators to release, including interleukin-1β (IL-1β), the processing and release of which are critically dependent on this ion channel activation. P2X7R’s therapeutic potential augments the discovery of new antagonistic compounds. Thus, we investigated whether the Eugenia sulcata essential oil could block P2X7R activity. The essential oil (ESO) dose-dependently inhibited ATP-promoted PI uptake and IL-1β release with an IC₅₀ of 113.3 ± 3.7 ng/mL and 274 ± 91 ng/mL, respectively, and the essential oil nanoemulsion (ESON) improved the ESO inhibitory effect with an IC₅₀ of 81.4 ± 7.2 ng/mL and 62 ± 2 ng/mL, respectively. ESO and ESON reversed the carrageenan-activated peritonitis in mice, and ESON exhibited an efficacy higher than ESO. The majority substance from essential oil, β-caryophyllene, impaired the ATP-evoked PI uptake and IL-1β release with an IC₅₀ value of 26 ± 0.007 ng/mL and 97 ± 0.012 ng/mL, respectively. Additionally, β-caryophyllene reduced carrageenan-induced peritonitis, and the molecular modeling and computational simulation predicted the intermolecular interactions in the P2X7R situs. In silico, results indicated β-caryophyllene as a potent allosteric P2X7R antagonist, although this substance may present toxic effects for humans. These data confirm the nanoemulsion of essential oil from E. sulcata as a promisor biotechnology strategy for impaired P2X7R functions and the inflammatory response. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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10 pages, 3976 KiB

Open AccessArticle

Cytotoxicity and Apoptosis Induction of 6,7-Dehydroroyleanone from Taiwania cryptomerioides Bark Essential Oil in Hepatocellular Carcinoma Cells

by Guan-Rong Chen, Mei-Ling Chang, Shang-Tzen Chang, Yu-Tung Ho and Hui-Ting Chang

Pharmaceutics 2022, 14(2), 351; https://doi.org/10.3390/pharmaceutics14020351 - 2 Feb 2022

Cited by 8 | Viewed by 2314

Abstract

The objective of the present study is to evaluate the cytotoxicity of Taiwania cryptomerioides essential oil and its phytochemical on the Hep G2 cell line (human hepatocellular carcinoma). Bark essential oil has significant cytotoxicity to Hep G2 cells, and S3 fraction is the [...] Read more.

The objective of the present study is to evaluate the cytotoxicity of Taiwania cryptomerioides essential oil and its phytochemical on the Hep G2 cell line (human hepatocellular carcinoma). Bark essential oil has significant cytotoxicity to Hep G2 cells, and S3 fraction is the most active fraction in cytotoxicity to Hep G2 cells among the six fractions. The diterpenoid quinone, 6,7-dehydroroyleanone, was isolated from the active S3 fraction by bioassay-guided isolation. 6,7-Dehydroroyleanone exhibited significant cytotoxicity in Hep G2 cells, and the efficacy of 6,7-dehydroroyleanone was better than the positive control, etoposide. Apoptosis analysis of Hep G2 cells with different treatments was characterized via flow cytometry to confirm the cell death situation. Etoposide and 6,7-dehydroroyleanone could induce the apoptosis in Hep G2 cells using flow cytometric assay. Results revealed 6,7-dehydroroyleanone from T. cryptomerioides bark essential oil can be a potential phytochemical to develop the anticancer chemotherapeutic agent for the treatment of the human hepatocellular carcinoma. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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9 pages, 7014 KiB

Open AccessArticle

Enzymatic Synthesis and Antimicrobial Activity of Oligomer Analogues of Medicinal Biopolymers from Comfrey and Other Species of the Boraginaceae Family

by Maia Merlani, Dieter M. Scheibel, Vakhtang Barbakadze, Lali Gogilashvili, Lela Amiranashvili, Athina Geronikaki, Valentina Catania, Domenico Schillaci, Giuseppe Gallo and Ivan Gitsov

Pharmaceutics 2022, 14(1), 115; https://doi.org/10.3390/pharmaceutics14010115 - 4 Jan 2022

Cited by 10 | Viewed by 2590

Abstract

This study reports the first enzymatic synthesis leading to several oligomer analogues of poly[3-(3,4-dihydroxyphenyl)glyceric acid]. This biopolymer, extracted from plants of the Boraginaceae family has shown a wide spectrum of pharmacological properties, including antimicrobial activity. Enzymatic ring opening polymerization of 2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane (MDBPO) using [...] Read more.

This study reports the first enzymatic synthesis leading to several oligomer analogues of poly[3-(3,4-dihydroxyphenyl)glyceric acid]. This biopolymer, extracted from plants of the Boraginaceae family has shown a wide spectrum of pharmacological properties, including antimicrobial activity. Enzymatic ring opening polymerization of 2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane (MDBPO) using lipase from Candida rugosa leads to formation of poly[2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane] (PMDBPO), with a degree of polymerization up to 5. Catalytic debenzylation of PMDBPO using H₂ on Pd/C yields poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO) without loss in molecular mass. Antibacterial assessment of natural polyethers from different species of Boraginaceae family Symhytum asperum, S. caucasicum,S. grandiflorum, Anchusa italica, Cynoglossum officinale, and synthetic polymers, poly[2-methoxycarbonyl-3-(3,4-dimethoxyphenyl)oxirane (PMDMPO) and PMDHPO, reveals that only the synthetic analogue produced in this study (PMDHPO) exhibits a promising antimicrobial activity against pathogenic strains S.aureus ATCC 25923 and E.coli ATCC 25922 the minimum inhibitory concentration (MIC) being 100 µg/mL. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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16 pages, 6219 KiB

Open AccessArticle

Oxyresveratrol Inhibits TNF-α-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation

by Nitwara Wikan, Phateep Hankittichai, Phatarawat Thaklaewphan, Saranyapin Potikanond and Wutigri Nimlamool

Pharmaceutics 2022, 14(1), 63; https://doi.org/10.3390/pharmaceutics14010063 - 28 Dec 2021

Cited by 11 | Viewed by 2833

Abstract

Psoriasis is a complex inflammatory disease characterized by hyperproliferative keratinocyte caused by active PI3K/AKT signaling. TNF-α concentrated in the psoriatic lesions stimulates AKT activation. We previously discovered that oxyresveratrol inhibited inflammation via suppressing AKT phosphorylation, therefore oxyresveratrol may possess a conserved property to [...] Read more.

Psoriasis is a complex inflammatory disease characterized by hyperproliferative keratinocyte caused by active PI3K/AKT signaling. TNF-α concentrated in the psoriatic lesions stimulates AKT activation. We previously discovered that oxyresveratrol inhibited inflammation via suppressing AKT phosphorylation, therefore oxyresveratrol may possess a conserved property to block AKT activation and proliferation in keratinocyte in response to TNF-α. Our current study proved that oxyresveratrol exhibited potent anti-proliferative effects against TNF-α. These effects are explained by the findings that oxyresveratrol could potentially inhibit TNF-α-stimulated AKT and GSK3-_β activation in a dose-dependent manner, and its inhibitory pattern was comparable to that of a specific PI3K inhibitor. Results from immunofluorescence supported that oxyresveratrol effectively inhibited AKT and GSK3-_β activation in individual cells upon TNF-α stimulation. Furthermore, functional assay confirmed that oxyresveratrol repressed the expansion of the HaCaT colony over 3 days, and this was caused by the ability of oxyresveratrol to induce cell cycle arrest at S and G2/M phases and the reduction in the expression of a proliferative marker (Ki-67) and a survival marker (MCL-1). Given the importance of TNF-α and the PI3K/AKT pathway in the psoriatic phenotype, we anticipate that oxyresveratrol, which targets the TNF-α-stimulated PI3K/AKT pathway, would represent a promising psoriasis therapy in the near future. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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20 pages, 1602 KiB

Open AccessArticle

Thermoresponsive Hydrogel Containing Viscum album Extract for Topic and Transdermal Use: Development, Stability and Cytotoxicity Activity

by João V. D. C. Batista, Ana Paula S. Matos, Adriana P. Oliveria, Eduardo Ricci Júnior, Zaida M. Freitas, Catarina A. Oliveira, Helena K. Toma, Marcia A. M. Capella, Leandro M. Rocha, Ulrike Weissenstein, Stephan Baumgartner and Carla Holandino

Pharmaceutics 2022, 14(1), 37; https://doi.org/10.3390/pharmaceutics14010037 - 24 Dec 2021

Cited by 9 | Viewed by 3339

Abstract

Viscum album L. (Santalaceae), also known as European mistletoe, is a semi-parasitic plant that grows on different host trees. Our group recently demonstrated the antitumoral activity of ethanolic V. album extracts in vitro, depending on the dose and the host tree, [...] Read more.

Viscum album L. (Santalaceae), also known as European mistletoe, is a semi-parasitic plant that grows on different host trees. Our group recently demonstrated the antitumoral activity of ethanolic V. album extracts in vitro, depending on the dose and the host tree, V. album ssp abietis from Abies alba being the most active extract. The goal of this work focused on the development of a new topical formulation containing V. album extracts, evaluation of in vitro toxicity and ex vivo skin permeation assays. The Poloxamer 407 hydrogel containing 5% of dry (VA_DEH) or aqueous (VA_AEH) extract presented dermal compatible pH and microbiological stability for 180 days. The hydrogels flow curve presented a non-linear relation, characteristic of non-Newtonian fluids, and the mean viscosity for the VA_DEH and VA_AEH was 372.5 ± 7.78 and 331.0 ± 2.83 Pa.s, respectively, being statistically different (Welch’s t test; p < 0.01). Additionally, WST-1 in vitro assays revealed a dose-dependent toxicity for both formulations and VA_DEH presented a higher activity than the VA_AEH. The promising cytotoxic potential of VA_DEH lead to the ex vivo skin permeation assay with 2.73 ± 0.19 µg/cm² of chlorogenic acid, which permeated at 8 h, showing a transdermal potential. These in vitro results support the idea that VA_DEH is a novel promising candidate for mistletoe therapy. Therefore, further in vivo and pre-clinical experiments should be performed to evaluate the safety and efficacy of this new dermic delivery system. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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18 pages, 21491 KiB

Open AccessArticle

Pro-Apoptotic Potential of Pseudevernia furfuracea (L.) Zopf Extract and Isolated Physodic Acid in Acute Lymphoblastic Leukemia Model In Vitro

by Martin Kello, Tomas Kuruc, Klaudia Petrova, Michal Goga, Zuzana Michalova, Matus Coma, Dajana Rucova and Jan Mojzis

Pharmaceutics 2021, 13(12), 2173; https://doi.org/10.3390/pharmaceutics13122173 - 16 Dec 2021

Cited by 8 | Viewed by 2952

Abstract

Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed type of leukemia among children. Although chemotherapy is a common treatment for cancer, it has a wide range of serious side effects, including myelo- and immunosuppression, hepatotoxicity and neurotoxicity. Combination therapies using natural substances [...] Read more.

Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed type of leukemia among children. Although chemotherapy is a common treatment for cancer, it has a wide range of serious side effects, including myelo- and immunosuppression, hepatotoxicity and neurotoxicity. Combination therapies using natural substances are widely recommended to attenuate the adverse effects of chemotherapy. The aim of the present study was to investigate the anti-leukemic potential of extract from the lichen Pseudevernia furfuracea (L.) Zopf (PSE) and isolated physodic acid (Phy) in an in vitro ALL model. A screening assay, flow cytometry and Western blotting were used to analyze apoptosis occurrence, oxidative stress, DNA damage and stress/survival/apoptotic pathway modulation induced by the tested substances in Jurkat cells. We demonstrate for the first time that PSE and Phy treatment-induced intrinsic caspase-dependent cell death was associated with increased oxidative stress, DNA damage and cell cycle arrest with the activation of cell cycle checkpoint proteins p53, p21 and p27 and stress/survival kinases p38 MAPK, JNK and PI3K/Akt. Moreover, using peripheral T lymphocytes, we confirmed that PSE and Phy treatment caused minimal cytotoxicity in normal cells, and therefore, these naturally occurring lichen secondary metabolites could be promising substances for ALL therapy. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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24 pages, 4627 KiB

Open AccessArticle

Prevention of Stress-Induced Depressive-like Behavior by Saffron Extract Is Associated with Modulation of Kynurenine Pathway and Monoamine Neurotransmission

by Camille Monchaux De Oliveira, Véronique De Smedt-Peyrusse, Jennifer Morael, Sylvie Vancassel, Lucile Capuron, David Gaudout, Line Pourtau and Nathalie Castanon

Pharmaceutics 2021, 13(12), 2155; https://doi.org/10.3390/pharmaceutics13122155 - 14 Dec 2021

Cited by 12 | Viewed by 3789

Abstract

Depressive disorders are a major public health concern. Despite currently available treatment options, their prevalence steadily increases, and a high rate of therapeutic failure is often reported, together with important antidepressant-related side effects. This highlights the need to improve existing therapeutic strategies, including [...] Read more.

Depressive disorders are a major public health concern. Despite currently available treatment options, their prevalence steadily increases, and a high rate of therapeutic failure is often reported, together with important antidepressant-related side effects. This highlights the need to improve existing therapeutic strategies, including by using nutritional interventions. In that context, saffron recently received particular attention for its beneficial effects on mood, although the underlying mechanisms are poorly understood. This study investigated in mice the impact of a saffron extract (Safr’Inside™; 6.25 mg/kg, per os) on acute restraint stress (ARS)-induced depressive-like behavior and related neurobiological alterations, by focusing on hypothalamic–pituitary–adrenal axis, inflammation-related metabolic pathways, and monoaminergic systems, all known to be altered by stress and involved in depressive disorder pathophysiology. When given before stress onset, Safr’Inside administration attenuated ARS-induced depressive-like behavior in the forced swim test. Importantly, it concomitantly reversed several stress-induced monoamine dysregulations and modulated the expression of key enzymes of the kynurenine pathway, likely reducing kynurenine-related neurotoxicity. These results show that saffron pretreatment prevents the development of stress-induced depressive symptoms and improves our understanding about the underlying mechanisms, which is a central issue to validate the therapeutic relevance of nutritional interventions with saffron in depressed patients. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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16 pages, 2225 KiB

Open AccessArticle

Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells

by Elisa Landucci, Francesca Bonomolo, Chiara De Stefani, Costanza Mazzantini, Domenico Edoardo Pellegrini-Giampietro, Anna Rita Bilia and Maria Camilla Bergonzi

Pharmaceutics 2021, 13(12), 2093; https://doi.org/10.3390/pharmaceutics13122093 - 5 Dec 2021

Cited by 18 | Viewed by 3776

Abstract

Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H₂O₂-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in [...] Read more.

Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H₂O₂-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in decreasing corneal neovascularization and reducing the inflammation in an experimental dry eye model in mice. Its therapeutic use is limited by poor bioavailability, low solubility, and scarce permeability. In this study, two liposomal formulations have been developed, both of which consist of phosphatidylcholine and Plurol Oleique, a liquid lipid, and one of which is coated with 0.1% w/v hyaluronic acid (HA) to increase both TQ solubility and its ocular therapeutic potential. Each formulation has a size <200 nm and an EE% around 70%, determined by scattering techniques and the HPLC-DAD analytical method, respectively, and they result in a 2-fold increase in TQ solubility. HA-coated liposomes are stable over 2 months at +4 °C, and coated and uncoated liposomes present a gradual and prolonged release of TQ. Two cell lines, human corneal epithelial cells (HCEC-2) and human conjunctival epithelial cells (HConEC) were used to investigate the safety of the liposomal formulations. Uptake studies were also performed using fluorescent liposomes. Both liposomes and, in particular, HA-coated liposomes reduce the TQ toxicity observed at high doses in both HCEC-2 and HConEC cells, and both formulations increase the absorption at the cellular level and especially at the nucleus level, with a more pronounced effect for HA-coated liposomes. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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25 pages, 6623 KiB

Open AccessArticle

Isolation, Structure Determination of Sesquiterpenes from Neurolaena lobata and Their Antiproliferative, Cell Cycle Arrest-Inducing and Anti-Invasive Properties against Human Cervical Tumor Cells

by Andrea Vasas, Ildikó Lajter, Norbert Kúsz, Sándor Balázs Király, Tibor Kovács, Tibor Kurtán, Noémi Bózsity, Nikolett Nagy, Zsuzsanna Schelz, István Zupkó, Georg Krupitza, Richard Frisch, Attila Mándi and Judit Hohmann

Pharmaceutics 2021, 13(12), 2088; https://doi.org/10.3390/pharmaceutics13122088 - 5 Dec 2021

Cited by 4 | Viewed by 2914

Abstract

Seven new germacranolides (1–3, 5–8), among them a heterodimer (7), and known germacranolide (4), eudesmane (9) and isodaucane (10) sesquiterpenes were isolated from the aerial parts of Neurolaena [...] Read more.

Seven new germacranolides (1–3, 5–8), among them a heterodimer (7), and known germacranolide (4), eudesmane (9) and isodaucane (10) sesquiterpenes were isolated from the aerial parts of Neurolaena lobata. Their structures were determined by using a combination of different spectroscopic methods, including HR-ESIMS and 1D and 2D NMR techniques supported by DFT-NMR calculations. The enantiomeric purity of the new compounds was investigated by chiral HPLC analysis, while their absolute configurations were determined by TDDFT-ECD and OR calculations. Due to the conformationally flexible macrocycles and difficulties in assigning the relative configuration, ¹³C and ¹H NMR chemical shift and ECD and OR calculations were performed on several stereoisomers of two derivatives. The isolated compounds (1–10) were shown to have noteworthy antiproliferative activities against three human cervical tumor cell line with different HPV status (HeLa, SiHa and C33A). Additionally, lobatolide C (6) exhibited substantial antiproliferative properties, antimigratory effect, and it induced cell cycle disturbance in SiHa cells. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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23 pages, 17506 KiB

Open AccessArticle

Cyclodextrin as Functional Carrier in Development of Mucoadhesive Tablets Containing Polygoni cuspidati Extract with Potential for Dental Applications

by Magdalena Paczkowska-Walendowska, Emilia Szymańska, Katarzyna Winnicka, Dominik Szwajgier, Ewa Baranowska-Wójcik, Marek A. Ruchała, Marek Simon and Judyta Cielecka-Piontek

Pharmaceutics 2021, 13(11), 1916; https://doi.org/10.3390/pharmaceutics13111916 - 12 Nov 2021

Cited by 13 | Viewed by 2793

Abstract

Polygoni cuspidati root is a resveratrol-rich source with anti-inflammatory, angiogenic and neuroprotective effects. The raw material was standardized for the content of resveratrol, for which there is a special justification for administration within the oral mucosa. To improve the solubility of resveratrol and [...] Read more.

Polygoni cuspidati root is a resveratrol-rich source with anti-inflammatory, angiogenic and neuroprotective effects. The raw material was standardized for the content of resveratrol, for which there is a special justification for administration within the oral mucosa. To improve the solubility of resveratrol and to assure its high content in plant material, an ultrasound-assisted extraction method was applied. The addition of cyclodextrin was found to increase the extraction efficiency of resveratrol (from 13 to 297 µg per 1 g of plant material in case of 50% ethanol extracts) and enhanced its antioxidant activity as compared to pure Polygoni cuspidati extract/resveratrol. Cyclodextrin plays the role of a functional extract regarding technological properties (increasing the extraction of resveratrol from the extract, improving mucoadhesive properties). Therefore, the aim of this study was to develop mucoadhesive tablets containing combinations of the Polygoni cuspidati extract with a cyclodextrin carrier for buccal delivery. The tests sequentially included extract preparation and characterization of its physical and biological properties and then formulation studies with a broad description of the prototype properties. The test results indicate that cyclodextrin increases the efficiency of resveratrol extraction from Polygoni cuspidati rhizome, which is a rich source of resveratrol, and its extract enclosed in a mucoadhesive tablet guarantees prolonged action at the site of administration. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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31 pages, 5229 KiB

Open AccessArticle

Novel Multitarget Hydroxamic Acids with a Natural Origin CAP Group against Alzheimer’s Disease: Synthesis, Docking and Biological Evaluation

by Margarita Neganova, Yulia Aleksandrova, Evgenii Suslov, Evgenii Mozhaitsev, Aldar Munkuev, Dmitry Tsypyshev, Maria Chicheva, Artem Rogachev, Olga Sukocheva, Konstantin Volcho and Sergey Klochkov

Pharmaceutics 2021, 13(11), 1893; https://doi.org/10.3390/pharmaceutics13111893 - 8 Nov 2021

Cited by 10 | Viewed by 3610

Abstract

Hydroxamic acids are one of the most promising and actively studied classes of chemical compounds in medicinal chemistry. In this study, we describe the directed synthesis and effects of HDAC6 inhibitors. Fragments of adamantane and natural terpenes camphane and fenchane, combined with linkers [...] Read more.

Hydroxamic acids are one of the most promising and actively studied classes of chemical compounds in medicinal chemistry. In this study, we describe the directed synthesis and effects of HDAC6 inhibitors. Fragments of adamantane and natural terpenes camphane and fenchane, combined with linkers of various nature with an amide group, were used as the CAP groups. Accordingly, 11 original target compounds were developed, synthesized, and exposed to in vitro and in vivo biological evaluations, including in silico methods. In silico studies showed that all synthesized compounds were drug-like and could penetrate through the blood–brain barrier. According to the in vitro testing, hydroxamic acids 15 and 25, which effectively inhibited HDAC6 and exhibited anti-aggregation properties against β-amyloid peptides, were chosen as the most promising substances to study their neuroprotective activities in vivo. All in vivo studies were performed using 5xFAD transgenic mice simulating Alzheimer’s disease. In these animals, the Novel Object Recognition and Morris Water Maze Test showed that the formation of hippocampus-dependent long-term episodic and spatial memory was deteriorated. Hydroxamic acid 15 restored normal memory functions to the level observed in control wild-type animals. Notably, this effect was precisely associated with the ability to restore lost cognitive functions, but not with the effect on motor and exploratory activities or on the level of anxiety in animals. Conclusively, hydroxamic acid 15 containing an adamantane fragment linked by an amide bond to a hydrocarbon linker is a possible potential multitarget agent against Alzheimer’s disease. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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16 pages, 2270 KiB

Open AccessArticle

Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431

by Mariya Vildanova, Polina Vishnyakova, Aleena Saidova, Victoria Konduktorova, Galina Onishchenko and Elena Smirnova

Pharmaceutics 2021, 13(11), 1813; https://doi.org/10.3390/pharmaceutics13111813 - 30 Oct 2021

Cited by 4 | Viewed by 2774

Abstract

Diterpenoid plant hormone gibberellic acid (GA) plays an important role in regulation of plant growth and development and is commonly used in agriculture for activation of plant growth and food production. It is known that many plant-derived compounds have miscellaneous biological effects on [...] Read more.

Diterpenoid plant hormone gibberellic acid (GA) plays an important role in regulation of plant growth and development and is commonly used in agriculture for activation of plant growth and food production. It is known that many plant-derived compounds have miscellaneous biological effects on animals and humans, influencing specific cellular functions and metabolic pathways. However, the effect of GA on animal and human cells remains controversial. We investigated the effect of GA on cultured human cell lines of epidermoid origin—immortalized non-tumorigenic keratinocytes HaCaT and carcinoma A431 cells. We found that at a non-toxic dose, GA upregulated the expression of genes associated with the ER stress response—CHOP, sXBP1, GRP87 in both cell lines, and ATF4 predominantly in A431 cells. We also showed that GA was more effective in upregulating the production of ER stress marker GRP78, autophagy marker LC3B-II, and differentiation markers involucrin and filaggrin in A431 cells than in HaCaT. We conclude that GA induces mild ER stress in both cell lines, followed by the activation of differentiation via upregulation of autophagy. However, in comparison with immortalized keratinocytes HaCaT, GA is more effective in inducing differentiation of carcinoma A431 cells, probably due to the inherently lower differentiation status of A431 cells. The activation of differentiation in poorly differentiated and highly malignant A431 cells by GA may lower the level of malignancy of these cells and decrease their tumorigenic potential. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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20 pages, 6924 KiB

Open AccessArticle

Regulation of ROS-Dependent JNK Pathway by 2’-Hydroxycinnamaldehyde Inducing Apoptosis in Human Promyelocytic HL-60 Leukemia Cells

by Kyung-Sook Chung, Chae-Bin Yoo, Jeong-Hun Lee, Hwi-Ho Lee, Sang-Eun Park, Hee-Soo Han, Su-Yeon Lee, Byoung-Mok Kwon, Jung-Hye Choi and Kyung-Tae Lee

Pharmaceutics 2021, 13(11), 1794; https://doi.org/10.3390/pharmaceutics13111794 - 26 Oct 2021

Cited by 11 | Viewed by 2837

Abstract

The present study demonstrated that 2′-hydroxycinnamaldehyde (2′-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expression, (3) cytochrome c release [...] Read more.

The present study demonstrated that 2′-hydroxycinnamaldehyde (2′-HCA) induced apoptosis in human promyelocytic leukemia HL-60 cells through the activation of mitochondrial pathways including (1) translocation of Bim and Bax from the cytosol to mitochondria, (2) downregulation of Bcl-2 protein expression, (3) cytochrome c release into the cytosol, (4) loss of mitochondrial membrane potential (ΔΨ_m), and (5) caspase activation. 2′-HCA also induced the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase1/2 (ERK1/2) in HL-60 cells. The pharmacological and genetic inhibition of JNK effectively prevented 2′-HCA-induced apoptosis and activator protein-1 (AP-1)-DNA binding. In addition, 2′-HCA resulted in the accumulation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH) and protein thiols (PSH) in HL-60 cells. NAC treatment abrogated 2′-HCA-induced JNK phosphorylation, AP-1-DNA binding, and Bim mitochondrial translocation, suggesting that oxidative stress may be required for 2′-HCA-induced intrinsic apoptosis. Xenograft mice inoculated with HL-60 leukemia cells demonstrated that the intraperitoneal administration of 2′-HCA inhibited tumor growth by increasing of TUNEL staining, the expression levels of nitrotyrosine and pro-apoptotic proteins, but reducing of PCNA protein expression. Taken together, our findings suggest that 2′-HCA induces apoptosis via the ROS-dependent JNK pathway and could be considered as a potential therapeutic agent for leukemia. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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16 pages, 25744 KiB

Open AccessArticle

Induction of Apoptosis by Isoalantolactone in Human Hepatocellular Carcinoma Hep3B Cells through Activation of the ROS-Dependent JNK Signaling Pathway

by Min Yeong Kim, Hyesook Lee, Seon Yeong Ji, So Young Kim, Hyun Hwangbo, Shin-Hyung Park, Gi-Young Kim, Cheol Park, Sun-Hee Leem, Su Hyun Hong and Yung Hyun Choi

Pharmaceutics 2021, 13(10), 1627; https://doi.org/10.3390/pharmaceutics13101627 - 6 Oct 2021

Cited by 17 | Viewed by 2597

Abstract

Isoalantolactone (IALT) is one of the isomeric sesquiterpene lactones isolated from the roots of Inula helenium L. IALT is known to possess various biological and pharmacological activities, but its anti-cancer mechanisms are not well understood. The aim of the present study was to [...] Read more.

Isoalantolactone (IALT) is one of the isomeric sesquiterpene lactones isolated from the roots of Inula helenium L. IALT is known to possess various biological and pharmacological activities, but its anti-cancer mechanisms are not well understood. The aim of the present study was to investigate the anti-proliferative effects of IALT in human hepatocellular carcinoma (HCC) cells and to evaluate the potential anti-cancer mechanisms. Our results demonstrated that IALT treatment concentration-dependently suppressed the cell survival of HCC Hep3B cells, which was associated with the induction of apoptosis. IALT increased the expression of death-receptor-related proteins, activated caspases, and induced Bid truncation, subsequently leading to cleavage of poly (ADP-ribose) polymerase. In addition, IALT contributed to the cytosolic release of cytochrome c by destroying mitochondrial integrity, following an increase in the Bax/Bcl-2 expression ratio. However, IALT-mediated growth inhibition and apoptosis were significantly attenuated in the presence of a pan-caspase inhibitor, suggesting that IALT induced caspase-dependent apoptosis in Hep3B cells. Moreover, IALT activated the mitogen-activated protein kinases signaling pathway, and the anti-cancer effect of IALT was significantly diminished in the presence of a potent c-Jun N-terminal kinase (JNK) inhibitor. IALT also improved the generation of intracellular reactive oxygen species (ROS), whereas the ROS inhibitor significantly abrogated IALT-induced growth reduction, apoptosis, and JNK activation. Furthermore, ROS-dependent apoptosis was revealed as a mechanism involved in the anti-cancer activity of IALT in a 3D multicellular tumor spheroid model of Hep3B cells. Taken together, our findings indicate that IALT exhibited anti-cancer activity in HCC Hep3B cells by inducing ROS-dependent activation of the JNK signaling pathway. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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12 pages, 1583 KiB

Open AccessArticle

Purification and Identification of Novel Antioxidant Peptides Isolated from Geoffroea decorticans Seeds with Anticoagulant Activity

by Juliana Cotabarren, Brenda Ozón, Santiago Claver, Javier Garcia-Pardo and Walter David Obregón

Pharmaceutics 2021, 13(8), 1153; https://doi.org/10.3390/pharmaceutics13081153 - 27 Jul 2021

Cited by 5 | Viewed by 2606

Abstract

Geoffroea decorticans is a xerophilous deciduous tree present in most arid forests of southern South America, which is commonly used in traditional medicine. The seeds of this tree have been previously investigated for their singular chemical composition, but their protein content has been [...] Read more.

Geoffroea decorticans is a xerophilous deciduous tree present in most arid forests of southern South America, which is commonly used in traditional medicine. The seeds of this tree have been previously investigated for their singular chemical composition, but their protein content has been poorly investigated. Herein, we report the isolation, purification, and characterization of a set of thermostable peptides derived from Geoffroea decorticans seeds (GdAPs) with strong antioxidant and anticoagulant activities. The most potent antioxidant peptides showed a half maximal inhibitory concentration (IC₅₀) of 35.5 ± 0.3 µg/mL determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH). They also caused a dose-dependent prolongation of the aPTT clotting time with an IC₅₀ value of ~82 µg/mL. Interestingly, MALDI-TOF/MS analysis showed the presence of three major peptides with low molecular weights of 2257.199 Da, 2717.165 Da, and 5422.002 Da. The derived amino-acid sequence of GdAPs revealed their unique structural features, exhibiting homology with various proteins present in the genome of Arachis hypogaea. All in all, our data suggest a direct applicability of GdAPs for pharmaceutical purposes. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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11 pages, 21720 KiB

Open AccessArticle

Olive Oil Lipophenols Induce Insulin Secretion in 832/13 β-Cell Models

by Maria Cristina Caroleo, Pierluigi Plastina, Alessia Fazio, Chiara La Torre, Fabrizio Manetti and Erika Cione

Pharmaceutics 2021, 13(7), 1085; https://doi.org/10.3390/pharmaceutics13071085 - 16 Jul 2021

Cited by 8 | Viewed by 3109

Abstract

Glycemic control is a mainstay of type 2 diabetes mellitus (T2DM) clinical management. Despite the continuous improvement in knowledge and progress in terms of treatment, the achievement of the physiologic metabolic profile is still an ongoing challenge in diabetic patients. Pancreatic β-cell line [...] Read more.

Glycemic control is a mainstay of type 2 diabetes mellitus (T2DM) clinical management. Despite the continuous improvement in knowledge and progress in terms of treatment, the achievement of the physiologic metabolic profile is still an ongoing challenge in diabetic patients. Pancreatic β-cell line INS-1 832/13 was used to assess the insulin secretagogue activity of hydroxytyrosyl oleate (HtyOle) and tyrosyl oleate (TyOle), two naturally occurring lipophenols deriving from the conjugation of oleic acid (OA) and hydroxytyrosol (Hty) or tyrosol (Ty), respectively. The insulin secretion was determined under a glucose-induced insulin secretion (GSIS) condition by the ELISA method. The potential involvement of G-protein-coupled receptor 40 (GPR40), also known as free fatty acid receptor 1 (FFAR1), was investigated by both molecular docking and functional pharmacological approaches. Herein, we demonstrated that HtyOle and TyOle exerted a facilitatory activity on insulin secretion under the GSIS condition. Moreover, we provided evidence that both lipophenols are natural modulators of FFAR1 receptor. From our results, the anti-diabetes properties associated with olive oil consumption can be partly explained by the HtyOle and TyOle effects. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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11 pages, 1959 KiB

Open AccessCommunication

Schisandrol A Exhibits Estrogenic Activity via Estrogen Receptor α-Dependent Signaling Pathway in Estrogen Receptor-Positive Breast Cancer Cells

by Dahae Lee, Young-Mi Kim, Young-Won Chin and Ki Sung Kang

Pharmaceutics 2021, 13(7), 1082; https://doi.org/10.3390/pharmaceutics13071082 - 15 Jul 2021

Cited by 11 | Viewed by 3681

Abstract

The aim of this study was to examine the estrogen-like effects of gentiopicroside, macelignan, γ-mangostin, and three lignans (schisandrol A, schisandrol B, and schisandrin C), and their possible mechanism of action. Their effects on the proliferation of the estrogen receptor (ER)-positive breast cancer [...] Read more.

The aim of this study was to examine the estrogen-like effects of gentiopicroside, macelignan, γ-mangostin, and three lignans (schisandrol A, schisandrol B, and schisandrin C), and their possible mechanism of action. Their effects on the proliferation of the estrogen receptor (ER)-positive breast cancer cell line (MCF-7) were evaluated using Ez-Cytox reagents. The expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), AKT, and estrogen receptor α (ERα) was measured by performing Western blot analysis. 17β-estradiol (E2), also known as estradiol, is an estrogen steroid and was used as a positive control. ICI 182,780 (ICI), an ER antagonist, was used to block the ER function. Our results showed that, except for gentiopicroside, all the compounds promoted proliferation of MCF-7 cells, with schisandrol A being the most effective; this effect was better than that of E2 and was mitigated by ICI. Consistently, the expression of ERK, PI3K, AKT, and ERα increased following treatment with schisandrol A; this effect was slightly better than that of E2 and was mitigated by ICI. Taken together, the ERα induction via the PI3K/AKT and ERK signaling pathways may be a potential mechanism underlying the estrogen-like effects of schisandrol A. This study provides an experimental basis for the application of schisandrol A as a phytoestrogen for the prevention of menopausal symptoms. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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11 pages, 3381 KiB

Open AccessArticle

Antimelanogenesis Effects of Leaf Extract and Phytochemicals from Ceylon Olive (Elaeocarpus serratus) in Zebrafish Model

by Chi-Ya Huang, I-Hsuan Liu, Xiang-Zhe Huang, Hui-Jen Chen, Shang-Tzen Chang, Mei-Ling Chang, Yu-Tung Ho and Hui-Ting Chang

Pharmaceutics 2021, 13(7), 1059; https://doi.org/10.3390/pharmaceutics13071059 - 10 Jul 2021

Cited by 15 | Viewed by 4379

Abstract

The melanogenesis inhibition effect in zebrafish (Danio rerio) and antityrosinase activity of the ethanolic extract and its phytochemicals from Ceylon olive (Elaeocarpus serratus Linn.) leaves were investigated in this study. Among the leaf extract and four soluble fractions, the ethyl [...] Read more.

The melanogenesis inhibition effect in zebrafish (Danio rerio) and antityrosinase activity of the ethanolic extract and its phytochemicals from Ceylon olive (Elaeocarpus serratus Linn.) leaves were investigated in this study. Among the leaf extract and four soluble fractions, the ethyl acetate soluble fraction exhibits the best antityrosinase and antimelanogenesis activities. One phenolic acid, gallic acid, and two flavonoids, myricetin and mearnsetin, are isolated from the active subfractions through the bioassay-guided isolation; their structures are elucidated based on the 1D and 2D NMR, FTIR, UV, and MS spectroscopic analyses. These compounds have significant antityrosinase activity whether using l-tyrosine or l-DOPA as the substrate; mearnsetin shows the optimal activity. In the enzyme kinetic investigation, both gallic acid and mearnsetin are the competitive-type inhibitors against mushroom tyrosinase, and myricetin acts as a mixed-type tyrosinase inhibitor. Leaf extract and an ethyl acetate soluble fraction show effective performance in the inhibition of melanin formation in zebrafish embryos. Mearnsetin also possesses a promising antimelanogenesis effect, which is superior to the positive control, arbutin. Results reveal that the Ceylon olive leaf extract and its phytochemicals, especially mearnsetin, have the potential to be used as antimelanogenesis and skin-whitening ingredients. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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15 pages, 2619 KiB

Open AccessArticle

The Influence of Selected Factors on the Aqueous Cryptotanshinone Solubility

by Justyna Kobryń, Jowita Dałek and Witold Musiał

Pharmaceutics 2021, 13(7), 992; https://doi.org/10.3390/pharmaceutics13070992 - 30 Jun 2021

Cited by 6 | Viewed by 2445

Abstract

The application of cryptotanshinone (CT), a diterpenoid obtained from the root of Salviae miltiorrhiza, is significantly hindered due to its poor aqueous solubility. The aim of the present research was to develop an optimal solvent for analytical and preparative procedures of prospective [...] Read more.

The application of cryptotanshinone (CT), a diterpenoid obtained from the root of Salviae miltiorrhiza, is significantly hindered due to its poor aqueous solubility. The aim of the present research was to develop an optimal solvent for analytical and preparative procedures of prospective dermal hydrogel formulations with CT. The influence of pH, temperature, and cosolvent presence on the solubility of CT was examined. Various components were applied to increase CT solubility, i.e., ethanol, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-(hydroxymethyl)-1,3-propanediol, 2,2′,2″-nitrilotriethanol, and triisopropanoloamine. The concentration of CT was analyzed by spectral and chromatographic methods, including UV–vis and HPLC methods. The increased solubility of CT was demonstrated in alkaline solvents with ethanol as a cosolvent. CT solutions doped with alcoholamines are more stable compared to CT solutions doped with NaOH. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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22 pages, 4840 KiB

Open AccessArticle

Inorganic Element Determination of Romanian Populus nigra L. Buds Extract and In Vitro Antiproliferative and Pro-Apoptotic Evaluation on A549 Human Lung Cancer Cell Line

by Brigitta Kis, Ioana Zinuca Pavel, Daniela Haidu, Mariana Nela Ștefănuț, Zorița Diaconeasa, Elena-Alina Moacă, Cristina Adriana Dehelean, Simona Șipos, Alexandra Ivan and Corina Danciu

Pharmaceutics 2021, 13(7), 986; https://doi.org/10.3390/pharmaceutics13070986 - 29 Jun 2021

Cited by 7 | Viewed by 2706

Abstract

Populus nigra L. is a plant from Salicaceae family, native in Europe. Many parts of this tree can be used as active ingredients, but the most valuable are the buds. In recent years, a growing number of studies reported their activity in the [...] Read more.

Populus nigra L. is a plant from Salicaceae family, native in Europe. Many parts of this tree can be used as active ingredients, but the most valuable are the buds. In recent years, a growing number of studies reported their activity in the development of a wide range of pharmacological activities including diabetes, cardiovascular diseases, and cancer. The aim of this study was to determine the phytochemical composition and to evaluate the inorganic elements’ concentration as well as the in vitro antiproliferative and pro-apoptotic potential of a Populus nigra L. buds extract collected from Timișoara (Romania) against A549 human lung cancer cell line. Populus nigra L. bud extract was found to contain twelve different phenolic compounds. The inorganic elements concentrations were below the limit of detection for Co, Pb, and As, whereas Cu = 6.66 µg/g; Cr = 0.79 µg/g; Ni = 3.28 µg/g; Fe = 39.00 µg/g; Zn = 14.84 µg/g; Mn = 0.59 µg/g; Al = 2109.87 µg/g; and Cd = 0.019 µg/g. The extract was tested for the in vitro antiproliferative and pro-apoptotic potential on A549 human lung cancer cell line using different concentrations, namely 10, 25, 50, 75, 100, and 150 μg/mL. Results have shown that poplar bud extract induced a significant decrease of tumor cell viability in a dose-dependent manner with an IC₅₀ = 72.49 μg/mL and blocked the cells in the G0/G1 phase of the cell cycle. Phenomena of early apoptosis (from 1.34 ± 0.33% control cells to 2.68 ± 0.62% at 150 µg/mL) and late apoptosis (from 1.43 ± 0.14% control cells to 5.15 ± 1.02% at 150 µg/mL) were detected by Annexin V-PI double staining. Poplar bud extract can be regarded as a promising candidate for future studies involving lung cancer. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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18 pages, 789 KiB

Open AccessArticle

Dehydroabietic Acid Microencapsulation Potential as Biofilm-Mediated Infections Treatment

by Iris Neto, Eva María Domínguez-Martín, Epole Ntungwe, Catarina P. Reis, Milica Pesic, Célia Faustino and Patrícia Rijo

Pharmaceutics 2021, 13(6), 825; https://doi.org/10.3390/pharmaceutics13060825 - 2 Jun 2021

Cited by 7 | Viewed by 3037

Abstract

The antimicrobial activity of dehydroabietic acid (DHA) for its use as an antibiofilm agent was tested in this work. DHA was assayed against a collection of Gram-positive, Gram-negative sensitive and resistant bacteria and yeasts through the minimum inhibitory concentration (MIC), MIC with Bioburden [...] Read more.

The antimicrobial activity of dehydroabietic acid (DHA) for its use as an antibiofilm agent was tested in this work. DHA was assayed against a collection of Gram-positive, Gram-negative sensitive and resistant bacteria and yeasts through the minimum inhibitory concentration (MIC), MIC with Bioburden challenge, minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), MBIC with Bioburden challenge and growth curve studies. Toxicological studies (Artemia salina, sulforhodamine B (SRB) assay) were done to assess if the compound had antimicrobial and not cytotoxic properties. Furthermore, microencapsulation and stability studies were carried out to evaluate the chemical behavior and stability of DHA. On MIC results, Gram-positive bacteria Staphylococcus aureus ATCC 1228 and Mycobacterium smegmatis ATCC 607 presented a high efficiency (7.81 µg/mL), while on Gram-negative bacteria the highest MIC value of 125 µg/mL was obtained by all Klebsiella pneumoniae strains and Escherichia coli isolate strain HSM 303. Bioburden challenge showed that MIC, MBIC and percentage biofilm inhibition (BI) values suffered alterations, therefore, having higher concentrations. MBIC values demonstrated that DHA has a higher efficiency against S. aureus ATCC 43866 with a percentage of BI of 75.13 ± 0.82% at 0.49 µg/mL. Growth curve kinetic profiles of DHA against S. aureus ATCC 25923 were observed to be bacteriostatic. DHA-alginate beads had a average size of 2.37 ± 0.20 and 2.31 ± 0.17 × 10³ µm² with an encapsulation efficiency (EE%) around 99.49 ± 0.05%, a protection percentage (PP%) of 60.00 ± 0.05% in the gastric environment and a protection efficiency (PE%) around 88.12 ± 0.05% against UV light. In toxicological studies DHA has shown IC₅₀ of 19.59 ± 7.40 µg/mL and a LC₅₀ of 21.71 ± 2.18%. The obtained results indicate that DHA is a promising antimicrobial candidate against a wide range of bacteria and biofilm formation that must be further explored. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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18 pages, 5055 KiB

Open AccessArticle

Comparative Metabolite Profile, Biological Activity and Overall Quality of Three Lettuce (Lactuca sativa L., Asteraceae) Cultivars in Response to Sulfur Nutrition

by Muna Ali Abdalla, Fengjie Li, Arlette Wenzel-Storjohann, Saad Sulieman, Deniz Tasdemir and Karl H. Mühling

Pharmaceutics 2021, 13(5), 713; https://doi.org/10.3390/pharmaceutics13050713 - 13 May 2021

Cited by 25 | Viewed by 3951

Abstract

The main objective of the present study was to assess the effects of sulfur (S) nutrition on plant growth, overall quality, secondary metabolites, and antibacterial and radical scavenging activities of hydroponically grown lettuce cultivars. Three lettuce cultivars, namely, Pazmanea RZ (green butterhead, V1), [...] Read more.

The main objective of the present study was to assess the effects of sulfur (S) nutrition on plant growth, overall quality, secondary metabolites, and antibacterial and radical scavenging activities of hydroponically grown lettuce cultivars. Three lettuce cultivars, namely, Pazmanea RZ (green butterhead, V1), Hawking RZ (green multi-leaf lettuce, V2), and Barlach RZ (red multi-leaf, V3) were subjected to two S-treatments in the form of magnesium sulfate (+S) or magnesium chloride (−S). Significant differences were observed under −S treatments, especially among V1 and V2 lettuce cultivars. These responses were reflected in the yield, levels of macro- and micro-nutrients, water-soluble sugars, and free inorganic anions. In comparison with the green cultivars (V1 and V2), the red-V3 cultivar revealed a greater acclimation to S starvation, as evidenced by relative higher plant growth. In contrast, the green cultivars showed higher capabilities in production and superior quality attributes under +S condition. As for secondary metabolites, sixteen compounds (e.g., sesquiterpene lactones, caffeoyl derivatives, caffeic acid hexose, 5-caffeoylquinic acid (5-OCQA), quercetin and luteolin glucoside derivatives) were annotated in all three cultivars with the aid of HPLC-DAD-MS-based untargeted metabolomics. Sesquiterpene lactone lactucin and anthocyanin cyanidin 3-O-galactoside were only detected in V1 and V3 cultivars, respectively. Based on the analyses, the V3 cultivar was the most potent radical scavenger, while V1 and V2 cultivars exhibited antibacterial activity against Staphylococcus aureus in response to S provision. Our study emphasizes the critical role of S nutrition in plant growth, acclimation, and nutritional quality. The judicious-S application can be adopted as a promising antimicrobial prototype for medical applications. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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19 pages, 7524 KiB

Open AccessArticle

Constituents of Chamaecrista diphylla (L.) Greene Leaves with Potent Antioxidant Capacity: A Feature-Based Molecular Network Dereplication Approach

by Paulo Gomes, Luis Quirós-Guerrero, Abraão Muribeca, José Reis, Sônia Pamplona, Anderson H. Lima, Mariele Trindade, Consuelo Silva, Jesus N. S. Souza, Jean A. Boutin, Jean-Luc Wolfender and Milton Silva

Pharmaceutics 2021, 13(5), 681; https://doi.org/10.3390/pharmaceutics13050681 - 10 May 2021

Cited by 10 | Viewed by 4786

Abstract

Chamaecrista diphylla (L.) Greene (Fabaceae/Caesalpiniaceae) is a herbaceous plant that is widely distributed throughout the Americas. Plants from this genus have been used in traditional medicine as a laxative, to heal wounds, and to treat ulcers, snake and scorpion bites. In the present [...] Read more.

Chamaecrista diphylla (L.) Greene (Fabaceae/Caesalpiniaceae) is a herbaceous plant that is widely distributed throughout the Americas. Plants from this genus have been used in traditional medicine as a laxative, to heal wounds, and to treat ulcers, snake and scorpion bites. In the present study, we investigated the chemical composition of Chamaecrista diphylla leaves through a mass spectrometry molecular network approach. The oxygen radical absorbance capacity (ORAC) for the ethanolic extract, enriched fractions and isolated compounds was assessed. Overall, thirty-five compounds were annotated for the first time in C. diphylla. Thirty-two of them were reported for the first time in the genus. The isolated compounds 9, 12, 24 and 33 showed an excellent antioxidant capacity, superior to the extract and enriched fractions. Bond dissociation energy calculations were performed to explain and sustain the antioxidant capacity found. According to our results, the leaves of C. diphylla represent a promising source of potent antioxidant compounds. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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20 pages, 2228 KiB

Open AccessArticle

Cymbopogon winterianus Essential Oil Attenuates Bleomycin-Induced Pulmonary Fibrosis in a Murine Model

by Lívia A. Tavares, Allan A. Rezende, Jymmys L. Santos, Charles S. Estevam, Ana M. O. Silva, Jaderson K. Schneider, John L. S. Cunha, Daniela Droppa-Almeida, Ivan J. Correia-Neto, Juliana C. Cardoso, Patricia Severino, Eliana B. Souto and Ricardo L. C. de Albuquerque-Júnior

Pharmaceutics 2021, 13(5), 679; https://doi.org/10.3390/pharmaceutics13050679 - 9 May 2021

Cited by 15 | Viewed by 3693

Abstract

The essential oil of Cymbopogon winterianus (EOCW) is a natural product with antioxidant, anti-inflammatory, and antifibrotic properties. We studied the effect of EOCW in the progression of histological changes of pulmonary fibrosis (PF) in a rodent model. The oil was obtained by hydrodistillation [...] Read more.

The essential oil of Cymbopogon winterianus (EOCW) is a natural product with antioxidant, anti-inflammatory, and antifibrotic properties. We studied the effect of EOCW in the progression of histological changes of pulmonary fibrosis (PF) in a rodent model. The oil was obtained by hydrodistillation and characterized using gas chromatography–mass spectrometry. Intratracheal instillation of bleomycin was performed in 30 rats to induce PF, while Sham animals were subjected to instillation of saline solution. The treatment was performed using daily oral administration of distilled water, EOCW at 50, 100, and 200 mg/kg, and deflazacort (DFC). After 28 days, hemogram and bronchoalveolar lavage fluid (BALF), tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were assayed. Histological grading of PF, immunohistochemical expression of α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were also analyzed. The EOCW major compounds were found to be citronellal, geraniol, and citronellol. EOCW significantly reduced inflammation in BALF, reduced MDA levels, and increased SOD activity. EOCW attenuated histological grading of PF and reduced immunohistochemical expression of α-SMA and TGF-β in a dose-dependent way, likely due to the reduction of oxidative stress, inflammation, and TGF-β-induced myofibroblast differentiation. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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22 pages, 6900 KiB

Open AccessArticle

Artocarpin Targets Focal Adhesion Kinase-Dependent Epithelial to Mesenchymal Transition and Suppresses Migratory-Associated Integrins in Lung Cancer Cells

by Nongyao Nonpanya, Kittipong Sanookpan, Nicharat Sriratanasak, Chanida Vinayanuwattikun, Duangdao Wichadakul, Boonchoo Sritularak and Pithi Chanvorachote

Pharmaceutics 2021, 13(4), 554; https://doi.org/10.3390/pharmaceutics13040554 - 14 Apr 2021

Cited by 14 | Viewed by 3273

Abstract

Focal adhesion kinase (FAK) controls several cancer aggressive potentials of cell movement and dissemination. As epithelial–mesenchymal transition (EMT) and the migratory-associated integrins, known influencers of metastasis, have been found to be linked with FAK activity, this study unraveled the potential pharmacological effect of [...] Read more.

Focal adhesion kinase (FAK) controls several cancer aggressive potentials of cell movement and dissemination. As epithelial–mesenchymal transition (EMT) and the migratory-associated integrins, known influencers of metastasis, have been found to be linked with FAK activity, this study unraveled the potential pharmacological effect of artocarpin in targeting FAK resulting in the suppression of EMT and migratory behaviors of lung cancer cells. Treatment with artocarpin was applied at concentrations of 0–10 μM, and the results showed non-cytotoxicity in lung cancer cell lines (A549 and H460), normal lung (BEAS-2B) cells and primary metastatic lung cancer cells (ELC12, ELC16, and ELC20). We also found that artocarpin (0–10 µM) had no effect on cell viability, proliferation, and migration in BEAS-2B cells. For metastasis-related approaches, artocarpin significantly inhibited cell migration, invasion, and filopodia formation. Artocarpin also dramatically suppressed anchorage-independent growth, cancer stem cell (CSC) spheroid formation, and viability of CSC-rich spheroids. For molecular targets of artocarpin action, computational molecular docking revealed that artocarpin had the best binding affinity of −8.0 kcal/mol with FAK protein. Consistently, FAK-downstream proteins, namely active Akt (phosphorylated Akt), active mTOR (phosphorylated mTOR), and Cdc42, and EMT marker and transcription factor (N-cadherin, Vimentin, and Slug), were found to be significantly depleted in response to artocarpin treatment. Furthermore, we found the decrease of Caveolin-1 (Cav-1) accompanied by the reduction of integrin-αν and integrin-β3. Taken together, these findings support the anti-metastasis potentials of the compound to be further developed for cancer therapy. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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14 pages, 2164 KiB

Open AccessCommunication

Antidiabetic Flavonoids from Fruits of Morus alba Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes

by Sung Ho Lim, Jae Sik Yu, Ho Seon Lee, Chang-Ik Choi and Ki Hyun Kim

Pharmaceutics 2021, 13(4), 526; https://doi.org/10.3390/pharmaceutics13040526 - 9 Apr 2021

Cited by 34 | Viewed by 4447

Abstract

Morus alba (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from M. alba and their [...] Read more.

Morus alba (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from M. alba and their underlying mechanisms of action. Consequently, in this study, the fruits of M. alba were investigated for potential antidiabetic natural products using 3T3-L1 adipocytes. Phytochemical analysis of the ethanolic extract of M. alba fruits, followed by high-performance liquid chromatography (HPLC), purification led to the isolation of two main compounds: rutin and quercetin-3-O-β-d-glucoside (Q3G). Long-term use of available drugs for treating type 2 diabetes ((T2D) is often accompanied by undesirable side effects, which have generated increased interest in the development of more effective and safer antidiabetic agents. Examination of the isolated compounds, rutin and Q3G, for antidiabetic or anti-obesity properties or both in 3T3-L1 adipocytes demonstrated that they both improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes. The compounds also showed a positive effect on lipid accumulation in adipocytes, suggesting that glucose uptake occurred through activation of the Akt and AMPK signaling pathway without inducing adipogenesis. Taken together, our findings suggest that rutin and Q3G in M. alba fruits have the potential to induce fewer side effects such as weight gain, and these active compounds could be potential therapeutic candidates for the management of T2D. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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11 pages, 827 KiB

Open AccessArticle

Purification and Characterization of a Novel Thermostable Papain Inhibitor from Moringa oleifera with Antimicrobial and Anticoagulant Properties

by Juliana Cotabarren, Santiago Claver, Juan Abreu Payrol, Javier Garcia-Pardo and Walter David Obregón

Pharmaceutics 2021, 13(4), 512; https://doi.org/10.3390/pharmaceutics13040512 - 8 Apr 2021

Cited by 9 | Viewed by 2976

Abstract

Plant cystatins (or phytocystatins) comprise a large superfamily of natural bioactive small proteins that typically act as protein inhibitors of papain-like cysteine proteases. In this report, we present the purification and characterization of the first phytocystatin isolated from Moringa oleifera (MoPI). MoPI has [...] Read more.

Plant cystatins (or phytocystatins) comprise a large superfamily of natural bioactive small proteins that typically act as protein inhibitors of papain-like cysteine proteases. In this report, we present the purification and characterization of the first phytocystatin isolated from Moringa oleifera (MoPI). MoPI has a molecular mass of 19 kDa and showed an extraordinary physicochemical stability against acidic pHs and high temperatures. Our findings also revealed that MoPI is one of the most potent cysteine protease inhibitors reported to date, with Ki and IC₅₀ values of 2.1 nM and 5.7 nM, respectively. More interestingly, MoPI presents a strong antimicrobial activity against human pathogens such as Enterococcus faecalis and Staphylococcus aureus. In addition, MoPI also showed important anticoagulant activity, which is an unprecedented property for this family of protease inhibitors. These results highlight the pharmaceutical potential of this plant and its derived bioactive molecules. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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10 pages, 2955 KiB

Open AccessCommunication

Identification of Bioactive Natural Product from the Stems and Stem Barks of Cornus walteri: Benzyl Salicylate Shows Potential Anti-Inflammatory Activity in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

by Dahae Lee, Akida Alishir, Tae Su Jang and Ki Hyun Kim

Pharmaceutics 2021, 13(4), 443; https://doi.org/10.3390/pharmaceutics13040443 - 25 Mar 2021

Cited by 5 | Viewed by 3058

Abstract

Cornus walteri (Cornaceae), known as Walter’s dogwood, has been used to treat dermatologic inflammation and diarrheal disease in traditional oriental medicine. As part of an ongoing research project to discover natural products with biological activities, the anti-inflammatory potential of compounds from C. walteri [...] Read more.

Cornus walteri (Cornaceae), known as Walter’s dogwood, has been used to treat dermatologic inflammation and diarrheal disease in traditional oriental medicine. As part of an ongoing research project to discover natural products with biological activities, the anti-inflammatory potential of compounds from C. walteri in lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages were explored. Phytochemical analysis of the methanol extract of the stem and stem bark of C. walteri led to the isolation of 15 chemical constituents. These compounds were evaluated for their inhibitory effects on the production of the proinflammatory mediator nitric oxide (NO) in LPS-stimulated macrophages, as measured by NO assays. The molecular mechanisms underlying the anti-inflammatory activity were investigated using western blotting. Our results demonstrated that among 15 chemical constituents, lupeol and benzyl salicylate inhibited NO production in LPS-activated RAW 264.7 macrophages. Benzyl salicylate was more efficient than N^G-monomethyl-L-arginine mono-acetate salt (L-NMMA) in terms of its inhibitory effect. In addition, the mechanism of action of benzyl salicylate consisted of the inhibition of phosphorylation of IκB kinase alpha (IKKα), IκB kinase beta (IKKβ), inhibitor of kappa B alpha (IκBα), and nuclear factor kappa B (NF-κB) in LPS-stimulated macrophages. Furthermore, benzyl salicylate inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Taken together, these results suggest that benzyl salicylate present in the stem and stem bark of C. walteri has potential anti-inflammatory activity, supporting the potential application of this compound in the treatment of inflammatory diseases. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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15 pages, 1930 KiB

Open AccessArticle

Ballodiolic Acid A and B: Two New ROS, (^•OH), (ONOO⁻) Scavenging and Potent Antimicrobial Constituents Isolated from Ballota pseudodictamnus (L.) Benth.

by Fozia, Asmat Shaheen, Ijaz Ahmad, Syed Badar Amin, Nisar Ahmad, Riaz Ullah, Ahmed Bari, Muhammad Sohaib, Mahmood Hafiz Majid and Abdulrahman Alobaid

Pharmaceutics 2021, 13(3), 402; https://doi.org/10.3390/pharmaceutics13030402 - 17 Mar 2021

Cited by 7 | Viewed by 2437

Abstract

Bioassays guided phytochemical investigations on the ethyl acetate-soluble fraction of the root material of Ballota pseudodictamnus (L.) Benth. led to the isolation of two new compounds, ballodiolic acid A (1) and ballodiolic acid B (2), along with three known [...] Read more.

Bioassays guided phytochemical investigations on the ethyl acetate-soluble fraction of the root material of Ballota pseudodictamnus (L.) Benth. led to the isolation of two new compounds, ballodiolic acid A (1) and ballodiolic acid B (2), along with three known compounds ballodiolic acid (3), ballotenic acid (4), and β-amyrin (5), which were also isolated for the first time from this species by using multiple chromatographic techniques. The structures of the compounds (1–5) were determined by modern spectroscopic analysis including 1D and 2D NMR techniques and chemical studies. In three separate experiments, the isolated compounds (1–5) demonstrated potent antioxidant scavenging activity, with IC₅₀ values ranging from 07.22–34.10 μM in the hydroxyl radical (^•OH) inhibitory activity test, 58.10–148.55 μM in the total ROS (reactive oxygen species) inhibitory activity test, and 6.23–69.01 μM in the peroxynitrite (ONOO⁻) scavenging activity test. With IC₅₀ values of (07.22 ± 0.03, 58.10 ± 0.07, 6.23 ± 0.04 μM) for ^•OH, total ROS, and scavenge ONOO⁻, respectively, ballodiolic acid B (2) showed the highest scavenging ability. Antibacterial and antifungal behaviors were also exposed to the pure compounds 1–5. In contrast to compounds 4 and 5, compounds 1–3 were active against all bacterial strains studied, with a good zone of inhibition proving these as a potent antibacterial agent. Similarly, compared to compounds 3–5, compounds 1 and 2 with a 47 percent and 45 percent respective inhibition zone were found to be more active against tested fungal strains. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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14 pages, 1655 KiB

Open AccessArticle

Taro Lectin Can Act as a Cytokine-Mimetic Compound, Stimulating Myeloid and T Lymphocyte Lineages and Protecting Progenitors in Murine Bone Marrow

by Erika Bertozzi de Aquino Mattos, Patricia Ribeiro Pereira, Lyris Anunciata Demétrio Mérida, Anna Carolina Nitzsche Teixeira Fernandes Corrêa, Maria Paula Vigna Freire, Vania Margaret Flosi Paschoalin, Gerlinde Agate Platais Brasil Teixeira, Maria de Fátima Brandão Pinho and Maurício Afonso Verícimo

Pharmaceutics 2021, 13(3), 350; https://doi.org/10.3390/pharmaceutics13030350 - 7 Mar 2021

Cited by 2 | Viewed by 2341

Abstract

Taro (Colocasia esculenta) corm is traditionally consumed as a medicinal plant to stimulate immune responses and restore a health status. Tarin, a taro lectin, is considered responsible for the immunomodulatory effects of taro. In the present study, in order to investigate [...] Read more.

Taro (Colocasia esculenta) corm is traditionally consumed as a medicinal plant to stimulate immune responses and restore a health status. Tarin, a taro lectin, is considered responsible for the immunomodulatory effects of taro. In the present study, in order to investigate the effects of tarin on bone marrow hematopoietic population, murine cells were stimulated with tarin combined with a highly enriched conditioned medium containing either IL-3 or GM-CSF. Cells challenged with tarin proliferated in a dose-dependent manner, evidenced by the increase in cell density and number of clusters and colonies. Tarin exhibited a cytokine-mimetic effect similar to IL-3 and GM-CSF, increasing granulocytic cell lineage percentages, demonstrated by an increase in the relative percentage of Gr-1+ cells. Tarin does not increase lymphocytic lineages, but phenotyping revealed that the relative percentage of CD3+ cells was increased with a concomitant decrease in CD19+ and IL-7Rα+ cells. Most bone marrow cells were stained with tarin-FITC, indicating non-selective tarin binding, a phenomenon that must still be elucidated. In conclusion, taro corms contain an immunomodulatory lectin able to boost the immune system by promoting myeloid and lymphoid hematopoietic progenitor cell proliferation and differentiation. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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27 pages, 890 KiB

Open AccessReview

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease

by Ancuta-Veronica Lupaescu, Monica Iavorschi and Mihai Covasa

Pharmaceutics 2022, 14(2), 235; https://doi.org/10.3390/pharmaceutics14020235 - 20 Jan 2022

Cited by 19 | Viewed by 4529

Abstract

It has become increasingly apparent that defective insulin signaling may increase the risk for developing Alzheimer’s disease (AD), influence neurodegeneration through promotion of amyloid formation or by increasing inflammatory responses to intraneuronal β-amyloid. Recent work has demonstrated that hyperglycemia is linked to cognitive [...] Read more.

It has become increasingly apparent that defective insulin signaling may increase the risk for developing Alzheimer’s disease (AD), influence neurodegeneration through promotion of amyloid formation or by increasing inflammatory responses to intraneuronal β-amyloid. Recent work has demonstrated that hyperglycemia is linked to cognitive decline, with elevated levels of glucose causing oxidative stress in vulnerable tissues such as the brain. The ability of β-amyloid peptide to form β-sheet-rich aggregates and induce apoptosis has made amyloid fibrils a leading target for the development of novel pharmacotherapies used in managing and treatment of neuropathological conditions such as AD-related cognitive decline. Additionally, deposits of β-sheets folded amylin, a glucose homeostasis regulator, are also present in diabetic patients. Thus, therapeutic compounds capable of reducing intracellular protein aggregation in models of neurodegenerative disorders may prove useful in ameliorating type 2 diabetes mellitus symptoms. Furthermore, both diabetes and neurodegenerative conditions, such as AD, are characterized by chronic inflammatory responses accompanied by the presence of dysregulated inflammatory biomarkers. This review presents current evidence describing the role of various small bioactive molecules known to ameliorate amyloidosis and subsequent effects in prevention and development of diabetes and AD. It also highlights the potential efficacy of peptide–drug conjugates capable of targeting intracellular targets. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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35 pages, 5021 KiB

Open AccessReview

Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

by Leontina Elena Filipiuc, Daniela Carmen Ababei, Teodora Alexa-Stratulat, Cosmin Vasilica Pricope, Veronica Bild, Raluca Stefanescu, Gabriela Dumitrita Stanciu and Bogdan-Ionel Tamba

Pharmaceutics 2021, 13(11), 1823; https://doi.org/10.3390/pharmaceutics13111823 - 1 Nov 2021

Cited by 41 | Viewed by 6587

Abstract

The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and [...] Read more.

The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and low appetite, is still a good candidate for the development of new compounds. If initially all attention was directed to the endocannabinoid system, recent studies suggest that many of the clinically proven effects are based on an intrinsic chain of mechanisms that do not necessarily involve only cannabinoid receptors. Recent research has shown that major phytocannabinoids and their derivatives also interact with non-cannabinoid receptors such as vanilloid receptor 1, transient receptor ankyrin 1 potential, peroxisome proliferator-activated receptor-gamma or glitazone receptor, G55 protein-coupled receptor, and nuclear receptor, producing pharmacological effects in diseases such as Alzheimer’s, epilepsy, depression, neuropathic pain, cancer, and diabetes. Nonetheless, further studies are needed to elucidate the precise mechanisms of these compounds. Structure modulation of phytocannabinoids, in order to improve pharmacological effects, should not be limited to the exploration of cannabinoid receptors, and it should target other courses of action discovered through recent research. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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20 pages, 993 KiB

Open AccessReview

Bulbous Plants Drimia: “A Thin Line between Poisonous and Healing Compounds” with Biological Activities

by Madira Coutlyne Manganyi, Gothusaone Simon Tlatsana, Given Thato Mokoroane, Keamogetswe Prudence Senna, John Frederick Mohaswa, Kabo Ntsayagae, Justine Fri and Collins Njie Ateba

Pharmaceutics 2021, 13(9), 1385; https://doi.org/10.3390/pharmaceutics13091385 - 1 Sep 2021

Cited by 9 | Viewed by 5119

Abstract

Drimia (synonym Urginea) plants are bulbous plants belonging to the family Asparagaceae (formerly the family Hyacinthaceae) and are distinctive, powerful medicinal plants. Just some species are indigenous to South Africa and have been traditionally utilized for centuries to cure various diseases and/or [...] Read more.

Drimia (synonym Urginea) plants are bulbous plants belonging to the family Asparagaceae (formerly the family Hyacinthaceae) and are distinctive, powerful medicinal plants. Just some species are indigenous to South Africa and have been traditionally utilized for centuries to cure various diseases and/or ailments. They have been recognized among the most famous and used medicinal plants in South Africa. Traditionally, the plants are used for various illnesses such as dropsy, respiratory disease, bone and joint complications, skin disorders, epilepsy and cancer. A number of studies have reported biological properties such as antiviral, antibacterial, antioxidant and anti-inflammatory, immunomodulatory, and anticancer activities. Their bulbs are a popular treatment for colds, measles, pneumonia, coughs, fever and headaches. However, some plant species are regarded as one of the six most common poisonous plants in Southern Africa that are toxic to livestock and humans. Due to the therapeutic effects of the Drimia plant bulb, research has focused on the phytochemicals of Drimia species. The principal constituents isolated from this genus are cardiac glycosides. In addition, phenolic compounds, phytosterols and other phytochemical constituents were identified. This study constitutes a critical review of Drimia species’ bioactive compounds, toxicology, biological properties and phytochemistry, advocating it as an important source for effective therapeutic medicine. For this purpose, various scientific electronic databases such as ScienceDirect, Scopus, Google Scholar, PubMed and Web of Science were researched and reviewed to conduct this study. Despite well-studied biological investigations, there is limited research on the toxic properties and the toxic compounds of certain Drimia species. Searching from 2017 to 2021, Google Scholar search tools retrieved 462 publications; however, only 3 investigated the toxicity and safety aspects of Drimia. The aim was to identify the current scientific research gap on Drimia species, hence highlighting a thin line between poisonous and healing compounds, dotted across numerous publications, in this review paper. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications)

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