Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor.

Md Afjalus Siraj,Veronique Seidel,Md Rahman,Ghee Tan

doi:10.3390/ijms22073595

Abstract

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

Highlights

The cannabinoid receptors (CB) belong to the superfamily of G protein-coupled receptors and are divided into two major types: CBR type-1 (CB1) and CBR type-2 (CB2)
Cannabinoids have already demonstrated great potential for the treatment of pain, inflammation, and neurodegenerative disorders [10,11,12]. These include the phytocannabinoids from Cannabis sativa and other plant-derived cannabinoid-like molecules called cannabimimetics that can interact with the endogenous cannabinoid system [13]
It has been reported that triterpenes, including α-amyrin and β amyrin, could induce in vivo antinociceptive and anti-inflammatory effects via activation of the cannabinoid receptors [24,26]

Summary

Introduction

The cannabinoid receptors (CB) belong to the superfamily of G protein-coupled receptors and are divided into two major types: CBR type-1 (CB1) and CBR type-2 (CB2). CB1 can be found in peripheral tissues including retina [4], colon [5], testis [6], sperm cells [7], and adipocytes [8]. CB2 receptors are mostly found in peripheral tissues [9]. Cannabinoids have already demonstrated great potential for the treatment of pain, inflammation, and neurodegenerative disorders [10,11,12]. These include the phytocannabinoids from Cannabis sativa and other plant-derived cannabinoid-like molecules called cannabimimetics that can interact with the endogenous cannabinoid system [13]

Methods

Results

Conclusion