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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).
Modulating effect of DL-kavain on the mutagenicity and carcinogenicity induced by doxorubicin in Drosophila melanogaster
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Thaís Teixeira da Silva, Júlia Braga Martins, Maria Do Socorro de Brito Lopes, Pedro Marcos de Almeida, José Luiz Silva Sá, Francielle Alline Martins
Kavalactones, individually or combined with methanolic kava extract, were reported to inhibit a number of cytochrome 450 (CYP450) isoforms, including CYP1A2, CYP2C9; CYP2C19; CYP2D6, CYP3A4; CYP4A9 and CYP4A9/11 (Mathews, Etheridge, and Black 2002; Mathews et al. 2005). This property is the source of numerous interactions, primarily pharmacokinetic, with other drugs, since kavalactones and kava extract decrease metabolism by blocking enzymes of the CYP450 complex, thereby inducing toxicity (Mathews, Etheridge, and Black 2002; Zou et al. 2004). The bioactivation and biotransformation pathways of kavain were reported in mice by Wang et al. (2019) who identified 28 metabolites in liver, urine and feces. CYP2C19, one of the CYP450 enzymes, was the major enzyme contributing to biotransformation and bioactivation of kavain. Although pharmacokinetic and/or pharmacodynamic studies have advanced knowledge over the years, only in vitro few studies were conducted to investigate the toxicogenetic potential of kavain and other kavalactones (Celentano et al. 2020; Li et al. 2012; Shaik, Hermanson, and Xing 2009; Zi and Simoneau 2005).