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(searched for: doi:10.1016/j.jep.2017.09.023)
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Jasmine M. Olvany, Scott M. Williams, Peter A. Zimmerman
Published: 15 November 2022
Frontiers in Pharmacology, Volume 13; https://doi.org/10.3389/fphar.2022.752314

Abstract:
Clinical trial and individual patient treatment outcomes have produced accumulating evidence that effective primaquine (PQ) treatment of Plasmodium vivax and P. ovale liver stage hypnozoites is associated with genetic variation in the human cytochrome P450 gene, CYP2D6. Successful PQ treatment of individual and population-wide infections by the Plasmodium species that generate these dormant liver stage forms is likely to be necessary to reach elimination of malaria caused by these parasites globally. Optimizing safe and effective PQ treatment will require coordination of efforts between the malaria and pharmacogenomics research communities.
Published: 12 May 2022
by MDPI
Journal: Molecules
Abstract:
Vitis vinifera (V. vinifera) is a herbaceous plant, cultivated worldwide and known for its biological benefits. The aim of this study is the investigation of the chemical composition as well as the determination of the biological potential of different grape stem extracts obtained by maceration and accelerated solvent extraction (ASE). The HPLC analysis of the tested extracts led to the identification of 28 compounds of which 17 were identified for the first time in grape plants, in addition to seven revealed in the stem part for the first time. Twenty-nine volatile molecules have been detected by GC-MS in the grape stem part; among them seven were identified for the first time in the grape plant. For the biological analysis, the ethyl acetate extract (EtOAc) obtained by maceration showed a significant potential regarding antioxidant activity (IC50 = 42.5 µg/mL), anti-Alzheimer (IC50 = 14.1 µg/mL), antidiabetic (IC50 = 13.4 µg/mL), cytotoxic with HCT-116 (IC50 = 12.5 µg/mL), and anti-inflammatory (IC50 = 26.6 µg/mL) activities, as well as showing the highest polyphenol content (207.9 mg GAE/g DW).
Evidence-Based Complementary and Alternative Medicine, Volume 2022, pp 1-28; https://doi.org/10.1155/2022/3829180

Abstract:
Mesosphaerum suaveolens (L.) Kuntze is a species widely used traditionally in the treatment of ailments, such as stomach pain, hemorrhoids, cough, verminosis, ulcer, liver disease, fever, influenza, nasal congestion, and inflammation. This review aims to provide a survey of available information on seven international electronic databases (Google Scholar, Medline, ResearchGate, Web of Science, Scopus, Science Direct, and PubMed) about botanical aspects, traditional uses, phytochemistry, and biological activities of M. suaveolens. Mesosphaerum suaveolens is a tropical America native species, but it can be found in several parts of the world as a ruderal plant. The species is the most studied species of the genus Lamiaceae due its phytochemical aspect, especially regarding the chemical composition of its essential oil. Besides the essential oils, M. suaveolens is a source of numerous secondary compounds such as triterpenes, diterpenes, and phenolic compounds, which are related to its biological activities, such as allelopathic, antibacterial, antifungal, insecticidal, and larvicidal activities as described in the literature.
, Ce Wang, Jinqian Chen, Xia Hu, Hao Zhang, Zhiying Li, Bei Lan, Wei Zhang, Yanjun Su, Chunze Zhang
Published: 19 January 2022
Toxicology Letters, Volume 358, pp 40-47; https://doi.org/10.1016/j.toxlet.2022.01.007

The publisher has not yet granted permission to display this abstract.
Published: 14 January 2022
by MDPI
Journal: Molecules
Abstract:
Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb–herb or herb–drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals’ effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.
Published: 14 June 2021
Biochemistry Research International, Volume 2021, pp 1-13; https://doi.org/10.1155/2021/9946183

Abstract:
Triumfetta welwitschii has been used as a traditional medicine in Africa. It is documented as a rich source of phytochemicals with antibacterial activities. To further explore the antibacterial potential of these phytochemical components, the phytochemical profile of the dichloromethane: methanol leaf extract from T. welwitschii was investigated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Compounds were isolated from the extract using column chromatography and thin-layer chromatography. Compound B1 was isolated from the fraction eluted by 90 hexane:10 ethyl acetate using column chromatography. The antibacterial activity of B1 against Pseudomonas aeruginosa was evaluated in vitro using the broth microdilution method and the iodonitrotetrazolium (INT) colorimetric assay. The antibiofilm activities of the extract and B1 against P. aeruginosa were determined by quantifying the biofilms using crystal violet. The effect of the extract and B1 on capsular polysaccharide and extracellular DNA content of biofilm formed by P. aeruginosa was determined using phenol-sulphuric acid and propidium iodide, respectively. A total of 28 peaks were detected and identified using UPLC-MS/MS. The three most abundant phytochemicals identified were catechin, umbelliferone, and a luteolin derivative. B1 showed antibacterial activity against P. aeruginosa with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) value of 25μg/ml. Only 38 and 6 of the biofilms were formed in the presence of the extract and B1, respectively. The extract and B1 reduced the capsular polysaccharide content in biofilms formed in P. aeruginosa by 40 and 65, respectively. The extract and B1 significantly reduced the extracellular DNA content of biofilms by 29 and 72, respectively. The results of this study provide evidence of the antibacterial and antibiofilm activities of B1 and leaf extracts from T. welwitschii. Future work should identify the chemical structure of B1 using nuclear magnetic resonance and mass spectrometry.
, E.A. Estrella-Parra, E. Nolasco-Ontiveros, , R. García-Hernández, , , , J. Del C. Benítez-Flores, , et al.
Published: 1 May 2021
Food and Chemical Toxicology, Volume 151; https://doi.org/10.1016/j.fct.2021.112095

Abstract:
Skin cancer is a public health problem due to its high incidence. Ultraviolet radiation (UVR) is the main etiological agent of this disease. Photochemoprotection involves the use of substances to avoid damage caused by UV exposure. The aim of this work was to determine the phytochemical fingerprint and photochemoprotective effect against UVB radiation-induced skin damage such as erythema and carcinogenesis of H. mociniana methanolic extract (MEHm). The chemical composition of the MEHm was analysed by LC/ESI-MS/MS. Three quercetin derivatives, two pectinolides, and two caffeic acid derivatives were identified in the methanolic extract. MEHm has antioxidant effect and it is not cytotoxic in HaCaT cells. Phytochemicals from H. mociniana have a photochemopreventive effect because they absorb UV light and protect HaCaT cells from UVR-induced cell death. Also, in SKH-1 mice -acute exposure-, it decreased erythema formation, modulating the inflammatory response, reduced the skin damage according to histological analysis and diminished p53 expression. Finally, MEHm protects from photocarcinogenesis by reducing the incidence and multiplicity of skin carcinomas in SKH-1 mice exposed chronically to UVB radiation.
Yurui Shi, Jing Xie, Rongda Chen, Guiming Liu, Yanzhou Tao, Yangyang Fan, Xiaolin Wang, Li Li,
Published: 25 November 2020
Biomedical Chromatography, Volume 35; https://doi.org/10.1002/bmc.5039

The publisher has not yet granted permission to display this abstract.
Henrique Bridi, Gabriela De Carvalho Meirelles,
Published: 5 August 2020
Journal of Ethnopharmacology, Volume 264, pp 113225-113225; https://doi.org/10.1016/j.jep.2020.113225

The publisher has not yet granted permission to display this abstract.
Lili Jiang, Zhen Wang, Xiaoyu Wang, Shujuan Wang,
Published: 22 May 2020
Toxicology in Vitro, Volume 67; https://doi.org/10.1016/j.tiv.2020.104890

The publisher has not yet granted permission to display this abstract.
Francisca Palomares-Alonso, , Guadalupe Concepción Vidal-Cantú, Irma Susana Rojas-Tomé, , , , Guadalupe Palencia Hernández, ,
Published: 9 April 2020
Revista Brasileira de Farmacognosia, Volume 30, pp 251-256; https://doi.org/10.1007/s43450-020-00058-w

The publisher has not yet granted permission to display this abstract.
Acharya Balkrishna, Sachin Shridhar Sakat, Ravikant Ranjan, Kheemraj Joshi, Sunil Shukla, Kamal Joshi, Sudeep Verma, Abhishek Gupta, Kunal Bhattacharya,
Published: 25 March 2020
Frontiers in Pharmacology, Volume 11; https://doi.org/10.3389/fphar.2020.00288

Abstract:
Divya Sarva-Kalp-Kwath (SKK) is a poly-herbal ayurvedic medicine formulated using plant extracts of Boerhavia diffusa L. (Nyctaginaceae), Phyllanthus niruri L. (Euphorbiaceae), and Solanum nigrum L. (Solanaceae), described to improve liver function and general health. In the present study, we have explored the hepatoprotective effects of SKK in ameliorating carbon tetrachloride (CCl4) induced liver toxicity using in-vitro and in-vivo test systems. Chemical analysis of SKK using Liquid Chromatography-Mass Spectroscopy (LC-MS-QToF) and High-Performance Liquid Chromatography (HPLC) revealed the presence of different bioactive plant metabolites, known to impart hepatoprotective effects. In human hepatocarcinoma (HepG2) cells, co-treatment of SKK with CCl4 effectively reduced the hepatotoxicity induced by the latter. These effects were confirmed by studying parameters such as loss of cell viability; release of hepatic injury enzymatic biomarkers- aspartate aminotransferase (AST), and alkaline phosphatase (ALP); and changes in reactive oxygen species and in mitochondrial membrane potentials. In-vivo safety analysis in Wistar rats showed no loss in animal body weight, or change in feeding habits after repeated oral dosing of SKK up to 1,000 mg/kg/day for 28 days. Also, no injury-related histopathological changes were observed in the animal's blood, liver, kidney, heart, brain, and lung. Pharmacologically, SKK played a significant role in modulating CCl4 induced hepatic injuries in the Wistar rats at a higher dose. In the 9 weeks' study, SKK (200 mg/kg) reduced the CCl4 stimulated increase in the release of enzymes (ALT, AST, and ALP), bilirubin, total cholesterol, and uric acid levels in the Wistar rats. It also reduced the CCl4 stimulated inflammatory lesions such as liver fibrosis, lymphocytic infiltration, and hyper-plasticity. In conclusion, SKK showed pharmacological effects in improving the CCl4 stimulated liver injuries in HepG2 cells and in Wistar rats. Furthermore, no adverse effects were observed up to 10× higher human equivalent dose of SKK during 28-days repeated dose exposure in Wistar rats. Based on the literature search on the identified plant metabolites, SKK was found to act in multiple ways to ameliorate CCl4 induced hepatotoxicity. Therefore, polyherbal SKK medicine has shown remarkable potentials as a possible alternative therapeutics for reducing liver toxicity induced by drugs, and other toxins.
Yuanyuan Fu, , Minhui Hu, Yulan Jiang, Peidong Chen, Yumei Chi, Sheng Yu, Li Zhang, Qinan Wu, Facheng Zhang, et al.
Journal of Pharmaceutical and Biomedical Analysis, Volume 174, pp 595-607; https://doi.org/10.1016/j.jpba.2019.06.030

The publisher has not yet granted permission to display this abstract.
Published: 25 May 2018
by MDPI
International Journal of Molecular Sciences, Volume 19; https://doi.org/10.3390/ijms19061578

Abstract:
The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review discusses plant-based natural product drug discovery and how innovative technologies play a role in next-generation drug discovery.
Published: 17 April 2018
by MDPI
Journal of Personalized Medicine, Volume 8; https://doi.org/10.3390/jpm8020015

Abstract:
The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data into a patient’s phenotype to guide drug therapy and is at the core of all CYP2D6 gene/drug pair guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The AS, however, only explains a portion of the variability observed among individuals and ethnicities. In this review, we provide an overview of sources in addition to CYP2D6 genotype that contribute to the variability in CYP2D6-mediated drug metabolism and discuss other factors, genetic and non-genetic, that likely contribute to the observed variability in CYP2D6 enzymatic activity.
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