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Herbs with Antidepressant Effects
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
Among the many phytochemical constituents of kava, known collectively as kavalactones or kavapyrones, are dihydrokawain, kawain, methysticin, yangonin, dihydromethysticin, desmethoxyyangonin, flavokawin A, pinostrobinchalcone, dihydrotectochrysin, alpinetinchalcone, alpinetin, dihydrooroxylin A, and others in lesser degrees of concentration.2 Six of these kavalactones, including kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin, are responsible for nearly all of the plant's pharmacological activity.
Catalog of Herbs
Published in James A. Duke, Handbook of Medicinal Herbs, 2018
Contains a greenish-yellow aromatic resin called kawine, and various alkaloids, with an abundance of starch.2 The extract dihydromethysticin may cause exfoliative dermatitis. Methysticin, dihydrokawain, and yangonin are also reported.11 Benzoic and cinnamic acids may have a local anesthetic action.5 Also, contains yangonin, 11-methoxyangonin, deme-thoxyyangonin, methysticin, dihydromethisticin, kawain, dihydrokawain, 5-dihydroyan-gonin, and tetrahydroyangonin.266
Inhibition of CYP2C9 by natural products: insight into the potential risk of herb-drug interactions
Published in Drug Metabolism Reviews, 2020
Kai Wang, Qing Gao, Tingting Zhang, Jinqiu Rao, Liqin Ding, Feng Qiu
In addition to the above described common types of naturally occurring compounds, there are some natural products with rare structural characteristics that also act as CYP2C9 inhibitors (Figure 2). Kavalactones, including desmethoxyyangonin (DMY), methysticin (M) and dihydromethysticin (DHM), have been reported to result in significant inhibition of CYP2C9. The most potent inhibitors, M and DHM, have a methylenedioxyphenyl moiety that is usually present in the structures of many of the alkaloids described above and could form metabolic intermediate complexes with a maximum absorption of 455 nm after incubation with HLMs and NADPH (Mathews et al. 2002). Many other types of polyphenolic compounds were also determined to be strong CYP2C9 inhibitors, such as the chalcones xanthohumol and phloretin (Yuan et al. 2014, Kimura et al. 2010). Rhapontigenin, a stilbene, was reported to be a potent inhibitor of CYP2C9 with an IC50 value of 2.7 μM. Rhapontigenin has several phenolic hydroxyl groups in its chemical structure, which is similar to the chemical structures of flavonoids (Cieniak et al. 2013). Another study reported that alkyl phenols isolated from Labisia pumila (Kacip Fatimah) were the material basis for CYP2C9 inhibition, which provided further evidence for the importance of phenolic hydroxyl groups (Manda et al. 2014).
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Kava (Piper methysticum) is an effective herbal medicine for anxiety and insomnia and has been consumed in Polynesia as a ceremonial and cultural drink for centuries. However, upon introduction as a dietary supplement in Western countries, there have been multiple case reports of kava-induced hepatotoxicity requiring liver transplantation (Becker et al. 2019). The major constituents of kava extracts are bioactive kavalactones including kawain, 7,8-dihydrokawain, methysticin, 7,8-dihydromethysticin, yangonin, and desmethoxyyangonin (Olsen et al. 2011). The two MDP-bearing lactones, methysticin and 7,8-dihydromethysticin, were shown to produce reactive o-quinones via initial CYP-mediated O-demethylenation of the MDP moiety to a catechol followed by two-electron oxidation (Johnson et al. 2003) (Figure 9(a)). GSH or mercapturic acid conjugates were not identified in human urine presumably due to extensive conjugation of the catechols via glucuronidation and sulfation in vivo. Detection of mercapturic acid adducts of 6-phenyl-3-hexen-2-one in human urine suggested an alternative bioactivation pathway of kavalactones (Zou et al. 2005). Scission of the pyrone ring followed by decarboxylation and o-demethylation led to formation of 6-phenyl-3-hexen-2-one, an α, β-unsaturated ketone metabolite which reacts with GSH or mercapturic acid via Michael-type addition (Zou et al. 2005).
Inhibition of UDP-glucuronosyltransferases by different furoquinoline alkaloids
Published in Xenobiotica, 2020
Yixuan Li, Weihua Zhang, Tingting Yin, Ce Wang, Feige Wang, Jing Sun, Lina Liu, Qinghuai Zhang, Chunze Zhang
Herbal medicines are increasingly applied for the prevention and treatment of various diseases. It is estimated that about 80% of global patients use herbal medicines for treatment, and most of them take herbal medicines and other compounds at the same time (Wang et al., 2015; Zhou et al., 2007). However, the use of herbal medicines is not without potential hazards. Herbs have adverse effects themselves, such as Herbae pulvis standardisatus, Larrea tridentate, methysticin and Cassia senna. They can exert severe adverse effects including liver or kidney damage, colon perforation, carcinoma, coma and death (Posadzki et al., 2013). Besides, the combination of herbal medicines with other drugs can cause negative reactions. For example, when taking aspirin and Ginkgo biloba concurrently, Ginkgo may increase the risk of bleeding caused by aspirin in older adults (Dergal et al., 2002). The cause of this phenomenon is due to herb–drug interactions (HDIs). HDIs include pharmacodynamic interactions and pharmacokinetic interactions. The former refers to the fact that one drug changes the pharmacological effect of another drug (van den Berg et al., 2017). The latter can influence the plasma concentration of herbs in the process of absorption, distribution, metabolism, and excretion. Drugs have the highest incidence of HDIs in metabolism, accounting for about 40% of pharmacokinetic interactions (Li et al., 2019; Meng & Liu, 2015). The inhibition of herbs and their main active ingredients towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons for HDIs (Lin & Liu, 1997). For example, the inhibition of Hydrastis canadensis on the important phase I DME cytochrome P450 (CYP) 2D6 has been demonstrated to affect the metabolism of debrisoquine (Gurley et al., 2008). Panax notoginseng saponins affect the metabolism of aspirin mainly by inhibiting the activity of human carboxylesterase 2 (Sun et al., 2018).