Evaluation of safety and in vitro mechanisms of anti-diabetic activity of β-caryophyllene and L-arginine

Abstract

Background and Objective: β-caryophyllene (BCP) and L-arginine (LA) have been found to have anti-inflammatory, insulinotropic and antioxidant activity. However, a mechanistic approach regarding the combination of BCP and LA against the inflammatory processes present in diabetes mellitus has not been explored. Hence, the current study's objective was to determine the in vitro mechanisms of anti-oxidant, anti-inflammatory and α-glucosidase inhibitory activity of BCP, LA and their combination. Materialsand Methods: in vitro cell viability (20-500 mM) was assessed using the MTT assay. Safety studies for BCP and LA were carried out for acute (2000 mg kg-1) and repeated dose toxicity (300,600,900 mg kg-1). In vitro anti-oxidant, anti-inflammatory and α-glucosidase activity of BCP, LA and their combination was evaluated at different concentrations (20-320 μg mL-1) using the DPPH assay, H2O2 scavenging capacity assay, RBC membrane stabilization method and α-glucosidase inhibitory assay. Results: BCP+LA showed higher cell viability than BCP at 500 μg mL-1 (86.8 vs. 72.9%). Safety studies showed BCP+LA to be safe at 2000 mg kg-1. BCP+LA was more potent than the individual agents in all the assays with >50% activity at half the concentrations of the individual agents (80,20 and 20 μg mL-1) for all the assays. The membrane stabilizing activity of BCP+LA was greater than the individual agents at 320 pg mL-1. BCP, LA and BCP+LA displayed concentration-dependent increase in activity in all the assays. Conclusion: BCP+LA was safeand has moreanti-oxidant, anti-inflammatory and α-glucosidase inhibitory activity than individual agents. These results give preliminary evidence supporting the combined use for the treatment of diabetes mellitus.