Pharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
Planta Med. 2019 Oct;85(14-15):1136-1142. doi: 10.1055/a-1008-9491. Epub 2019 Sep 20.
Monoamine oxidases (MAOs) are key metabolic enzymes for neurotransmitter and dietary amines and are targets for the treatment of neuropsychiatric and neurodegenerative disorders. This study examined the MAO inhibition potential of kavain and other kavalactones from the roots of kava (), a plant that has been used for its anxiolytic properties. (±)-Kavain was found to be a good potency inhibitor of human MAO-B with an IC of 5.34 µM. (±)-Kavain is a weaker MAO-A inhibitor with an IC of 19.0 µM. Under the same experimental conditions, the reference MAO inhibitor, curcumin, displays IC values of 5.01 µM and 2.55 µM for the inhibition of MAO-A and MAO-B, respectively. It was further established that (±)-kavain interacts reversibly and competitively with MAO-A and MAO-B with enzyme-inhibitor dissociation constants (K) of 7.72 and 5.10 µM, respectively. Curcumin in turn, displays a K value of 3.08 µM for the inhibition of MAO-A. Based on these findings, other kavalactones (dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) were also evaluated as MAO inhibitors in this study. Yangonin proved to be the most potent MAO inhibitor with IC values of 1.29 and 0.085 µM for MAO-A and MAO-B, respectively. It may be concluded that some of the central effects (e.g., anxiolytic) of kava may be mediated by MAO inhibition.
单胺氧化酶（MAO）是神经递质和膳食胺的关键代谢酶，也是治疗神经精神和神经退行性疾病的靶点。本研究考察了卡瓦胡椒（）根中的卡瓦酮和其他卡瓦内酯对 MAO 的抑制潜力，卡瓦胡椒是一种具有抗焦虑特性的植物。（±）-卡瓦酮对人 MAO-B 的抑制能力较强，IC 为 5.34 μM。（±）-卡瓦酮是一种较弱的 MAO-A 抑制剂，IC 为 19.0 μM。在相同的实验条件下，参考 MAO 抑制剂姜黄素对 MAO-A 和 MAO-B 的抑制 IC 值分别为 5.01 μM 和 2.55 μM。进一步证实（±）-卡瓦酮与 MAO-A 和 MAO-B 相互作用可逆且具有竞争性，酶抑制剂解离常数（K）分别为 7.72 和 5.10 μM。姜黄素对 MAO-A 的抑制 K 值为 3.08 μM。基于这些发现，本研究还评估了其他卡瓦内酯（二氢卡瓦酮、甲氧基卡瓦酮、二氢甲氧基卡瓦酮、洋川芎内酯和去甲氧基洋川芎内酯）作为 MAO 抑制剂。洋川芎内酯对 MAO-A 和 MAO-B 的抑制能力最强，IC 值分别为 1.29 和 0.085 μM。可以得出结论，卡瓦的一些中枢作用（如抗焦虑作用）可能是通过 MAO 抑制介导的。
