Methysticin (M) #6
Methysticin (meth-this-ta-sin)
Methysticin, identified as number 6 in chemotypes because of its ability to be the final kavalactone to depart the HPLC column within a span of 32–37 min [1], possesses several distinctive roles. In rat hippocampal models, methysticin demonstrated anticonvulsant and neuroprotective properties. It has been observed to inhibit all forms of epileptiform discharges, which equates to induced epilepsy [2]. Furthermore, studies have shown that methysticin stimulates the induction of CYP1A1 [3]. Although CYP1A1 can activate compounds with carcinogenic properties [4], methysticin has been recognized for its protective qualities against oxidative stress and chronic inflammation, thereby reducing tumorigenesis. In a separate mouse-based study, methysticin was found to considerably enhance the deterioration of long-term memory in Alzheimer’s disease models. In addition, methysticin activates the Nrf2/ARE system in the mouse hippocampus, reducing the secretion of cytokines, which are instrumental in the progression of Alzheimer’s disease [5].
[1] Lebot, V. and J. Levesque. “The origin and distribution of kava piper methysticum forst. f. piperaceae a phytochemical approach.” (1989).
[2] Schmitz D, Zhang CL, Chatterjee SS, Heinemann U. Effects of methysticin on three different models of seizure like events studied in rat hippocampal and entorhinal cortex slices. Naunyn Schmiedebergs Arch Pharmacol. 1995 Apr;351(4):348-55. doi: 10.1007/BF00169074. PMID: 7630425. (https://pubmed.ncbi.nlm.nih.gov/7630425/)
[3] li, Yan & Mei, Hu & Wu, Qiangen & Zhang, Suhui & Fang, jia-long & Shi, Leming & Guo, Lei. (2011). Methysticin and 7,8-Dihydromethysticin are Two Major Kavalactones in Kava Extract to Induce CYP1A1. Toxicological sciences : an official journal of the Society of Toxicology. 124. 388-99. 10.1093/toxsci/kfr235. (https://academic.oup.com/toxsci/article-abstract/124/2/388/1685738?redirectedFrom=fulltext)
[4] Androutsopoulos, V.P., Tsatsakis, A.M. & Spandidos, D.A. Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC Cancer 9, 187 (2009). https://doi.org/10.1186/1471-2407-9-187
[5] Fragoulis, Athanassios & Fragoulis, Stephanie & Fendt, Markus & Jansen, Sandra & Soppa, Ulf & Brandenburg, Lars-Ove & Pufe, Thomas & Weis, Joachim & Wruck, Christoph. (2017). Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer´s disease. Redox Biology. 12. 10.1016/j.redox.2017.04.024. (https://doi.org/10.1016/j.redox.2017.04.024)