Kavalactones

Kavain is the principal kavalactone found in the roots of the kava plant (Piper methysticum), where it contributes significantly to the plant's psychoactive and anxiolytic effects.

Desmethoxyyangonin or 5,6-dehydrokavain is one of the six main kavalactones found in the Piper methysticum (kava) plant. It is a reversible inhibitor of monoamine oxidase B (MAO-B), likely contributing to increased dopamine levels in the brain's nucleus accumbens and supporting kava's attention-enhancing effects. Unlike other kavalactones, it does not modulate GABAA receptors. It also strongly induces the liver enzyme CYP3A23. It is an active compound in Alpinia pricei with anti-inflammatory and liver-protective effects that improve survival in mice with endotoxin-induced hepatitis.

300px|thumb|right|The general structure of the kavalactones, without the R1-R2 -O-CH2-O- bridge and with all possible C=C double bonds shown. Kavalactones are a class of lactone compounds found in kava roots and Alpinia zerumbet (shell ginger) and in several Gymnopilus, Phellinus and Inonotus fungi. Some kavalactones are bioactive. They are responsible for the psychoactive, analgesic, euphoric and sedative effects of kava.

Methysticin is one of the six major kavalactones found in the kava plant. It enhances the activity of the GABAA receptor, acting as a positive modulator without affecting the benzodiazepine binding site. This effect is attributed to structural features such as its angular lactone ring and is similar in strength to other kavalactones like kavain and dihydromethysticin. Methysticin also induces the liver enzyme CYP1A1, which plays a role in the toxification of benzo[a]pyrene into a highly carcinogenic metabolite, although such induction has not been observed in vivo in humans or animals. Additio

Dihydromethysticin is one of the six major kavalactones found in the kava plant. It is known for its anxiolytic, analgesic, and anticonvulsant properties. It induces the liver enzymes CYP1A1 and CYP3A through mechanisms involving the aryl hydrocarbon receptor and potentially pregnane X receptor-independent transcriptional activation. Dihydromethysticin acts synergistically with other kavalactones, modulates NMDA receptors and voltage-dependent calcium channels, and functions as a GABAA receptor positive allosteric modulator and monoamine oxidase B inhibitor. Dihydromethysticin shows high syste

Yangonin is one of the six major kavalactones found in the kava plant. It acts as a selective agonist at the CB1 cannabinoid receptor, inhibits monoamine oxidase (particularly MAO-B), and modulates GABAA receptor activity. Yangonin significantly reduces nociception and inflammatory hyperalgesia via spinal CB1 receptors in rats, highlighting its potential as a promising treatment for pain. It is the strongest COX-II inhibitor among the six major kavalactones. Yangonin also exhibits neuroprotective, antifungal, and antimicrobial properties, though it has shown toxicity to human hepatocytes in vi

Dihydrokavain is one of the six major kavalactones found in the kava plant. It showed the highest systemic exposure among all six major kavalactones tested, indicating it may play a central role in kava's pharmacological effects in humans. The anxiolytic effects of kava are primarily attributed to dihydrokavain.