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

Giuseppina Chianese; Carmina Sirignano; Emanuele Benetti; Vittoria Marzaroli; Juan A Collado; Lauren de la Vega; Giovanni Appendino; Eduardo Muñoz; Orazio Taglialatela-Scafati

doi:10.1021/acs.jnatprod.1c01198

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

Giuseppina Chianese
, Carmina Sirignano
, Emanuele Benetti
, Vittoria Marzaroli
, Juan A Collado
, Lauren de la Vega
, Giovanni Appendino
, Eduardo Muñoz
, Orazio Taglialatela-Scafati (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

272 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	1089-1097
Number of pages	9
Journal	Journal of Natural Products
Volume	85
Issue number	4
Early online date	22 Mar 2022
DOIs	https://doi.org/10.1021/acs.jnatprod.1c01198
Publication status	Published - 22 Apr 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cannabidiol/pharmacology
Cannabinoids/chemistry
Cannabis/chemistry
Chromatography, Liquid
Tandem Mass Spectrometry/methods

ASJC Scopus subject areas

Drug Discovery
Analytical Chemistry
Molecular Medicine
Complementary and alternative medicine
Pharmacology
Pharmaceutical Science
Organic Chemistry

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10.1021/acs.jnatprod.1c01198Licence: CC BY

Final Published VersionFinal published version, 1.63 MBLicence: CC BY

Cite this

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title = "A Nrf-2 Stimulatory Hydroxylated Cannabidiol Derivative from Hemp (Cannabis sativa)",

abstract = "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.",

keywords = "Cannabidiol/pharmacology, Cannabinoids/chemistry, Cannabis/chemistry, Chromatography, Liquid, Tandem Mass Spectrometry/methods",

author = "Giuseppina Chianese and Carmina Sirignano and Emanuele Benetti and Vittoria Marzaroli and Collado, \{Juan A\} and \{de la Vega\}, Lauren and Giovanni Appendino and Eduardo Mu{\~n}oz and Orazio Taglialatela-Scafati",

note = "Funding Information: This research was funded by MIUR, research grant PRIN2017, Project WN73PL (Bioactivity-directed exploration of the phytocannabinoid chemical space). Copyright {\textcopyright} 2022 The Authors. Published by American Chemical Society and American Society of Pharmacognosy.",

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language = "English",

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AU - Chianese, Giuseppina

AU - Sirignano, Carmina

AU - Benetti, Emanuele

AU - Marzaroli, Vittoria

AU - Collado, Juan A

AU - de la Vega, Lauren

AU - Appendino, Giovanni

AU - Muñoz, Eduardo

AU - Taglialatela-Scafati, Orazio

N1 - Funding Information: This research was funded by MIUR, research grant PRIN2017, Project WN73PL (Bioactivity-directed exploration of the phytocannabinoid chemical space). Copyright © 2022 The Authors. Published by American Chemical Society and American Society of Pharmacognosy.

PY - 2022/4/22

Y1 - 2022/4/22

N2 - 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.

AB - 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.

KW - Cannabidiol/pharmacology

KW - Cannabinoids/chemistry

KW - Cannabis/chemistry

KW - Chromatography, Liquid

KW - Tandem Mass Spectrometry/methods

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U2 - 10.1021/acs.jnatprod.1c01198

DO - 10.1021/acs.jnatprod.1c01198

M3 - Article

C2 - 35316044

SN - 0163-3864

VL - 85

SP - 1089

EP - 1097

JO - Journal of Natural Products

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IS - 4

ER -

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

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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