Concept

Kavalactone

Kavalactones are a class of lactone compounds found in kava roots and Alpinia zerumbet (shell ginger). Kavalactones are under research for potential to have various psychotropic effects, including anxiolytic and sedative/hypnotic activities. Kava extract has been shown in vitro to potentially inhibit a wide range of hepatic enzymes, suggesting a possible potential for interactions with many pharmaceuticals and herbal medications. In human volunteers in vivo inhibition is currently limited to CYP1A2, and CYP2E1 through use of probe drugs to measure inhibition. Several preliminary studies are assessing potential effects of kava, including its anxiolytic actions and hepatotoxicity, but the role specifically of kavalactones among many other kava compounds for these effects remains under study. The major kavalactones (except for desmethoxyyangonin) have been shown to potentiate the activity of GABAA receptors, which may underlie the anxiolytic and sedative properties of kava. Further, inhibition of the reuptake of norepinephrine and dopamine, binding to the CB1 receptor, inhibition of voltage-gated sodium and calcium channels, and monoamine oxidase B reversible inhibition are additional pharmacological actions that have been reported for kavalactones. Kavalactone type compounds may help protect against high glucose induced cell damage. Several kavalactones (e.g. methysticin and yangonin) affect a group of enzymes involved in metabolism, called CYP1A1. Hepatotoxicity occurred in a small portion of previously healthy kava users, particularly from extracts, as opposed to whole root powders. Flavokavain At least 18 different kavalactones have been identified to date, with methysticin being the first identified. Multiple analogues, such as ethysticin, have also been isolated. Some consist of a substituted α-pyrone as the lactone while others are partially saturated. The average elimination half-life of kavalactones typically present in kava root is 9 hr. The kavalactone biosynthetic pathway in Piper methysticum was described in 2019.

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Kava
Kava or kava kava (Piper methysticum: Latin 'pepper' and Latinized Greek 'intoxicating') is a crop of the Pacific Islands. The name kava is from Tongan and Marquesan, meaning 'bitter'; other names for kava include ʻawa (Hawaiʻi), ʻava (Samoa), yaqona or yagona (Fiji), sakau (Pohnpei), seka (Kosrae), and malok or malogu (parts of Vanuatu). Kava is consumed for its sedating effects throughout the Pacific Ocean cultures of Polynesia, including Hawaii and Vanuatu, Melanesia, some parts of Micronesia, such as Pohnpei and Kosrae, and the Philippines.

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