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Role of Natural Agents in the Management of Diabetes
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Monika Elżbieta Jach, Anna Serefko
Commiphora mucul, as an herbal tree with a resinous secretion, is one of the most valuable remedies in the traditional Ayurvedic medicine, especially for its antidiabetic, anti-oxidant, and anti-inflammatory activities (Kumar et al., 2016, Sudhakara et al., 2012). It has not well-defined chemical composition. Phyto-chemical studies of C. mucul indicate its content of sugars such as fructose or sucrose, amino acids, oil, and several steroids. However, only guggulsterone, as a bioactive sterol, has been purified from an ethyl-acetate extract of the gum guggul (Cornick et al., 2009). The essential oil of guggulsterone and guggul was found to be an efficient antioxidant (Siddiqui et al., 2013).
Guggulsterones
Published in Amritpal Singh Saroya, Contemporary Phytomedicines, 2017
Guggulsterone (Figs. 22.1, 22.2) is a plant steroid found in the resin of the guggul plant, Commiphoramukul. Guggulsterone can exist as either of two stereoisomers, ^-guggulsterone and Z-guggulsterone.
The Role of Nutrition and Nutritional Supplements in the Treatment of Dyslipidemia
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
Guggulipids are resins from the Mukul myrrh tree (Commiphora wightii) that contain active lipid-lowering compounds called guggulsterones.5,119–121 These increase hepatic LDL receptors, bile acid secretion, and decrease cholesterol synthesis in animal experiments.5,119 However, controlled human clinical trials have not shown these agents to be effective in improving serum lipids.119–121 One study of 103 subjects on 50–75 mg of guggulsterones per day for 8 weeks actually had a 5% increase in LDL, no change in TC, TG, or HDL, and insignificant reductions in Lp(a) and HS-CRP.119 Guggulipids are not recommended at this time.
Possible Herb-Drug Interaction Risk of Some Nutritional and Beauty Supplements on Antiretroviral Therapy in HIV Patients
Published in Journal of Dietary Supplements, 2022
Mona H. Haron, Bharathi Avula, PhD, Bill J. Gurley, PhD, Amar G. Chittiboyina, PhD, Ikhlas A. Khan, PhD, Shabana I. Khan, PhD
Given that phytochemicals and conventional drugs interact with human proteins in a similar manner, there is a high potential for such combinations to alter drug efficacy. In vitro studies have shown that phytochemicals abundant in our diet can influence human enzymatic pathways, potentially influencing the pharmacokinetics and pharmacodynamics of clinical drugs when consumed concomitantly (Sacco et al. 2008). In a recent clinical report, the concurrent use of guggulsterone-containing supplements by a HIV-infected patient treated with elvitegravir (exclusively metabolized by CYP3A isoforms) resulted in a significant reduction in plasma drug concentrations and a failure to achieve undetectable viral loads after four months of treatment (Elliot et al. 2017). Guggulsterone, a triterpenoid phytochemical found in a variety of multi-ingredient dietary supplements, is a PXR agonist, which induces the expression of several cytochrome P450 enzymes including CYP3A4, thereby leading to increased drug metabolism (Brobst et al. 2004; Yamada et al., 2016). More recognized PXR agonist drugs such as rifampicin, phenobarbital, and dexamethasone are potent inducers of CYP3A4 and perpetrators of clinically relevant drug-drug interactions. The importance of nuclear receptor activation compared to other gene-modulating mechanisms is highlighted by the fact that HepG2 cells transiently transfected with CYP3A4 promoters but not with PXR resulted in negligible increases in luciferase activity when treated with these therapeutics (Raucy 2003).
Gut microbial bile acid metabolite skews macrophage polarization and contributes to high-fat diet-induced colonic inflammation
Published in Gut Microbes, 2020
Lingyu Wang, Zizhen Gong, Xiuyuan Zhang, Fangxinxing Zhu, Yuchen Liu, Chaozhi Jin, Xixi Du, Congfeng Xu, Yingwei Chen, Wei Cai, Chunyan Tian, Jin Wu
Deoxycholic acid (DCA) and JTE-013 were purchased from Sigma-Aldrich (St. Louis, MO). Z-Guggulsterone was purchased from Santa cruz Biotechnology (Santa cruz, CA). Phospherylated and total ERK, JNK, IκB antibodies and SP600125, SB 203580, U0126 were purchased from Cell Signaling Technologies (Beverly, MA). Vancomycin, QNZ and SKI-606 were obtained from Selleckchem (Houston, TX). Methoctramine was purchased from AdooQ Bioscience (Irvine, CA). SR 11302 was purchased from APExBIO (Houston, TX). C29 was obtained from MedChemExpress (Monmouth Junction, NJ). TLR2, Src antibodies were from Abcam and phosphotyrosine antibody (4G10) was from Millipore. ELISA Kits were obtained from eBioscience (San Diego, CA).
FXR activation prevents liver injury induced by Tripterygium wilfordii preparations
Published in Xenobiotica, 2021
Wan Peng, Man-Yun Dai, Li-Juan Bao, Wei-Feng Zhu, Fei Li
The toxic effects of TWT are shown in Figure 8. The release of AST was increased during the 24 h in HepG2 cells exposed to TWT at 1000–5000 times (dilution multiple). Compared with the vehicle control, there were significant differences in AST activity (TWT at 1000–5000 times). HepG2 cells were pre-treated with a FXR inhibitor guggulsterone (Yang et al.2018a, Wei et al.2021) and subsequently exposed to TWT to induce damage. Guggulsterone at a concentration of 1 μM or 5 μM significantly increased the levels of AST compared with TWT (p < 0.05). These data indicated that inhibited FXR increased the hepatotoxicity in vitro.