In vitro studies on metabolism of salvinorin A

Abstract

Microbial transformation of natural products is a well established model for mammalian metabolism. Salvinorin A, a diterpenoid isolated from the hallucinogenic mint Salvia divinorum Epling & Játiva-M (Lamiaceae), is a potent non-nitrogenous κ-opioid receptor agonist. The metabolism of salvinorin A has still not yet been well established. Thirty fungal species were screened for the ability to metabolize salvinorin A. We observed that salvinorin A undergoes fast hydrolysis of the acetate group at carbon atom C2, resulting in formation of the pharmacologically inactive product, salvinorin B. Ex vivo experiments were also performed using organelle fractions isolated from rat liver and brain. Crude tissue homogenate and individual organelles show that the primary route of salvinorin A metabolism is hydrolysis to salvinorin B. No metabolic transformation of salvinorin B was observed in these studies.

Keywords::

• In vitro metabolism
• microbial transformation
• Salvia divinorum
• salvinorin A

Acknowledgements

The authors would like to acknowledge Ms. Kelly Thomas for her help during experiments with microbes, Ms. Anna Kochanowska for recording mass spectra, Dr. Jiangnan Peng for 600 MHz NMR of salvinorin B, and Dr. Asok Dasmahapatra for helpful suggestions during ex vivo experiments.

Declaration of interest: Financial support for one of the authors (L.M.K.) came from NIUST grant NA16RU1496, another (V.T.K.) was supported by the Peptide Radioiodination Service Center of the University of Mississippi, and research funds came from NIH Grant P20 RR 021929-01 from the National Center for Research Resources and CDC Grant U50/CCU418839-01. The work was conducted in a facility constructed with support from research improvement program grant C06 RR-14503-01 from the National Institutes of Health, Bethesda, MD, USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.