Agathadiol, a labdane diterpenoid from juniper berries, is a positive allosteric modulator of CB1R

Abstract

The neutral fraction of a juniper (Juniperus communis L.) berries acetone extract could positively modulate the activity of type 1 - cannabinoid receptor (CB₁R). Bioactivity-directed fractionation identified the labdane diterpenoid agathadiol (4) as a positive allosteric modulator of CB₁R, while closely related analogues were inactive. Agathadiol (4) is a minor constituent of juniper, but could be more conveniently obtained by semisynthesis from agathic acid (8), a major constituent of Manila copal.

Keywords: Agathadiol; Allosteric ligands; Cannabinoid receptor-1; Juniperus communis; Labdane diterpenoids.