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Herbal Supplements and Health
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Himangini Bansal, Sakshi Bajaj
Kava, a herbal sedative with antianxiety or calming effects, is prepared by extracting the rhizomes of Piper methysticum, a south pacific plant. There are at least 72 different cultivars of this species, which differ both in appearance and in chemical composition. The active chemicals of the plants, known as kavalactones, are concentrated in the rhizomes. Inhabitants of the south pacific islands prepare a kava-based drink by mixing fresh or dried rhizomes with cold water or coconut milk. Among more than 18 kavalactones characterized, 6 are considered the primary constituents of kava extracts: kawain, dihydrokawain, methysticine, dehydromethysticine, yangonin, and desmethoxyyangonin. Quite a considerable lot of these compounds, particularly those with a methylenedioxyphenyl derivatives (methysticine and dihydromethysticine), have been found to restrain various cytochrome P450s: CYP2C19, CYP1A2, CYP2C9, CYP3A4, CYP2D6, and CYPA4. It is therefore astonishing to discover that pharmacokinetic interactions among kava and Western medications are generally rare and are not very much reported in the literature. There is a case report that kava decreases the viability of levodopa (Dasgupta and Hammett-Stabler, 2010).
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.
On the Sophistication of Herbal Medicines
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
Such complexities are hardly limited to the berberine plants. The anticonvulsant actions of the kava lactones in Piper methysticum (i.e., yangonin and desmethoxyyangonin) are much stronger when used in combination with other kava constituents that are generally considered irrelevant in any standardization missives. As well, concentrations of yangonin and another lactone, kavain, are much higher in the brain when the whole plant extract is used instead of the purified lactones themselves. In other words, some of the other constituents in kava help move the bioactive lactones across the blood/brain barrier and into the brain where they will do the most good. Blood plasma concentrations of kavain are reduced by 50% if the purified compound is used rather than an extract of the plant itself.
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).