Nepofein: Nepodin-Caffeic Acid Ester for Therapy of Cancers and Diabetes?

We recently heard from an old Korean friend that a naphthalene called “Nepodin” (MW=216) from roots of an Okinawa weed is a potent anti-diabetic compound which activates the anti-oncogenic kinase AMPK (1).  It is effective at the daily dose of 2-10 mg/kg in mice. Interestingly, it was shown by a leading Korean pharmaceutical company (CKD) to be a potent anti-malaria drug as well (2).  

Almost all herbal AMPK activators are PAK1-blockers, and both diabetes (type 2) and malaria infection require the oncogenic/ageing kinase PAK1. Thus, it is not unreasonable to suspect that Nepodin also blocks PAK1. Interestingly, CAPE (caffeic acid phenethyl ester), the major anti-cancer/anti-PAK1 ingredient in propolis, is made simply by condensation of CA (caffeic acid) and phenethyl alcohol.  Thus, by analogy, it would be quite easy to synthesize a new ester called “Nepofein” by condensation of Nepodin and CA, and test its anti-cancer and anti-diabetic property, in which the CKD Pharm would be surely interested. http://www.ckdpharm.com

References:

1.   Ha BG, Yonezawa T, Son MJ, Woo JT, Ohba S, Chung UI, Yagasaki K. Antidiabetic effect of nepodin, a component of Rumex roots, and its modes of action in vitro and in vivo. Biofactors. 2014; 40(4): 436-47.

2.  Lee KH¹, Rhee KH. Antimalarial activity of nepodin isolated from Rumex crispus. Arch Pharm Res. 2013; 36(4):430-5.