A Nrf-2 Stimulatory Hydroxylated Cannabidiol Derivative from Hemp (Cannabis sativa)

A phytochemical analysis of mother liquors obtained from crystallization of CBD from hemp (Cannabis sativa), guided by LC-MS/MS and molecular networking profiling and completed by isolation and NMR-based characterization of constituents, resulted in the identification of 13 phytocannabinoids. Among them, anhydrocannabimovone (5), isolated for the first time as a natural product, and three new hydroxylated CBD analogues (1,2-dihydroxycannabidiol, 6, 3,4-dehydro-1,2-dihydroxycannabidiol, 7, and hexocannabitriol, 8) were obtained. Hexocannabitriol (8) potently modulated, in a ROS-independent way, the Nrf2 pathway, outperforming all other cannabinoids obtained in this study and qualifying as a potential new chemopreventive chemotype against cancer and other degenerative diseases.

Automated summary

A phytochemical analysis of mother liquors obtained from crystallization of CBD from hemp (Cannabis sativa) resulted in the identification of 13 phytocannabinoids. Among them, anhydrocannabimovone was isolated for the first time as a natural product, and three new hydroxylated CBD analogues were obtained. One of the hydroxylated phytocannabinoids, hexocannabitriol, showed potent modulation of the Nrf2 pathway and has potential as a new chemopreventive compound against cancer and other degenerative diseases.