Introduction to Kavalactones — Part 4: Yangonin and Desmethoxyyangonin
This article provides an examination of the scientific literature concerning kava and kavalactones. It is important to note that this article is not intended to serve as an endorsement for diagnosing, treating, preventing, or curing any disease.
In our ongoing exploration of kavalactones, we delve into yangonin and desmethoxyyangonin, the final two of the six major kavalactone compounds found in kava.
The key chemical difference between yangonin and desmethoxyyangonin lies in their structures. Yangonin contains a methoxy group (-OCH3) at the C4 position of its molecule, whereas desmethoxyyangonin lacks this methoxy group. This structural variation may influence their pharmacological activities and binding affinities to specific receptors, thereby impacting their overall effects in biological systems.
Yangonin, a prominent kavalactone abundant in kava, exerts profound pharmacological actions by modulating neurotransmitter systems, particularly the gamma-aminobutyric acid (GABA) system. It acts as a positive allosteric modulator of GABA-A receptors, enhancing GABAergic neurotransmission, and may contribute to the anxiolytic and sedative effects of kava preparations (1). Yangonin was also found to be the most potent monoamine oxidase (MAO) inhibitor, which is a property of many antidepressants and other central nervous system disorder pharmaceuticals (2).
Yangonin has also shown some promising results in preclinical in vitro models of cancer. In a model of bladder cancer, yangonin was shown to induce autophagy (3). In models of oral squamous cell carcinoma, yangonin demonstrated potential anticancer effects (4).
Like yangonin, desmethoxyyangonin enhances GABAergic neurotransmission and contributes to the calming effects of kava (1). While slightly less potent than yangonin, desmethoxyyangonin plays a crucial role in modulating GABA receptors and neuronal excitability.
Desmethoxyyangonin also shows activity at MAO receptors which may have important therapeutic significance for the treatment of neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease (5).
Understanding the pharmacological properties of yangonin and desmethoxyyangonin is vital for optimizing their therapeutic applications. From their roles in neurotransmitter modulation to their potential anticancer benefits, these kavalactones deserve further exploration to fully understand their potential.
References:
1. Baum SS, Hill R, Rommelspacher H. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Prog Neuropsychopharmacol Biol Psychiatry. 1998;22(7):1105-20.
2. Prinsloo D, van Dyk S, Petzer A, Petzer JP. Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum). Planta Med. 2019 Oct;85(14-15):1136-1142. doi: 10.1055/a-1008-9491. Epub 2019 Sep 20. PMID: 31539917.
3. Liu, Z.; Ha, U.S.; Yu, K.; Wu, C.; Yokoyama, N.; Zi, X. Kavalactone yangonin induces autophagy and sensitizes bladder cancer cells to flavokawain A and docetaxel via inhibition of the mTOR pathway. J. Biomed. Res. 2017, 31, 408–418.
4. Celentano A, Yiannis C, Paolini R, Zhang P, Farah CS, Cirillo N, Yap T, McCullough M. Kava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro. Sci Rep. 2020 Sep 28;10(1):15904. doi: 10.1038/s41598-020-73058-4. PMID: 32985597; PMCID: PMC7522996.
5. Chaurasiya ND, León F, Ding Y, Gómez-Betancur I, Benjumea D, Walker LA, Cutler SJ, Tekwani BL. Interactions of Desmethoxyyangonin, a Secondary Metabolite from Renealmia alpinia, with Human Monoamine Oxidase-A and Oxidase-B. Evid Based Complement Alternat Med. 2017;2017:4018724. doi: 10.1155/2017/4018724. Epub 2017 Aug 24. PMID: 29138643; PMCID: PMC5613693.