Protecting Pancreatic β-cells from Metabolic Insults
Christophe Wiart in Medicinal Plants in Asia for Metabolic Syndrome, 2017
Guggulsterone from the gum resin of Commiphora mukul (Hook. ex Stocks) Engl. at a concentration of 25 µM increased the survival of rat pancreatic β RIN cells challenged with inteleukin-1β and interferon-γ by 80% and prevented cytokine-induced reduction of cell proliferation.157 This treatment suppressed cytokine-induced activation of nuclear factor-κB and subsequent expression of inducible nitric oxide synthetase, nitric oxide generation, cyclo-oxygenase-2 expression and prostaglandin-E2 production.157 Besides, guggulsterone attenuated cytokine-induced phosphorylation and nuclear translocation of STAT-1 and STAT-3 and prevented the downregulation of SOCS-3.157 At a concentration of 25 µM, this sterol protected in vitro rat pancreatic islets against interleukin-1β and interferon-γ induced decrease in glucose-induced insulin secretion.157 In β-cells, interferon-γ induce the activation of STAT-1 and downstream activation of inducible nitric oxide synthetase. Besides, SOCS-3 is a known inhibitor of nuclear factor-κB and downstream expression of inducible nitric oxide synthetase.157 Guggulsterone at a concentration of 50 mM has been shown to decreases growth factor induced STAT 1/3 phosphorylation and therefore their translocation to the nucleus and to inhibit phosphoinositide 3-kinase in cancer cell.158 Human exposure to the gum resin of Commiphora mukul (Hook. ex Stocks) Engl. include skin rashes (Kölönte et al. 2006) as well as acute liver failure.159,160
Role of Natural Agents in the Management of Diabetes
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
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).
Types of Raw Incense
Kerry Hughes in The Incense Bible, 2014
Myrrh has long traditional and current uses beyond incense use including as a dye; the charcoal is used for cleaning teeth, strengthening the gums, and for wound healing; and a preparation of the bark has been used to treat skin disease (Quezada, 2003). The resins from the various species of myrrh have been particularly used for medicinal purposes in Indian, Arabian, and African cultures. In India the indigenous species (C. wightii) is well known for its use in medicine. Its guggulsterones have been well studied, and the resin, called guggulipid is well known to be hypolipidemic, anti-inflammatory, and antioxidant, and is often used as an adjuvunct to treating high cholesterol. Guggulsterone has been confirmed to lower cholesterol in clinical studies, and is also a potent antioxidant (Wang et al., 2004). Guggulipid is also used for treating arthritis, rheumatism, and other vascular conditions (Soehartono and Newton, 2002). C. myrrha is used by Middle Easterners for numerous reasons, including as an antimicrobial agent, stimulant, mouthwash, for the stomach, and for cancer. The myrrh resin from this species has been proven to be an antioxidant and antitumor agent that also is able to stimulate the thyroid and reduce prostaglandins. In preclinical studies, it performed well as a standard anticancer drug, cyclophosphamide, in its antitumor activity. Moreover, a couple of its sesquiterpenes have been shown to have potent analgesic activity. M. guidottii contains T-cadinol, which has smooth-muscle relaxing properties (Langenheim, 2004). Myrrh has several similar medicinal qualities as frankincense because they share some of the same terpenoids in their resin (Langenheim, 2004).
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.
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