Pro-inflammatory cytokine molecules from Boswellia serrate suppresses lipopolysaccharides induced inflammation demonstrated in an in-vivo zebrafish larval model.

Abstract

Boswellia serrate is an ancient and highly valued ayurvedic herb. Its extracts have been used in medicine for centuries to treat a wide variety of chronic inflammatory diseases. However, the mechanism by which B. serrata hydro alcoholic extract inhibited pro-inflammatory cytokines in zebrafish (Danio rerio) larvae with LPS-induced inflammation remained unknown. LC-MS analysis was used to investigate the extract's phytochemical components. To determine the toxicity of B. serrata extract, cytotoxicity and embryo toxicity tests were performed. The in-vivo zebrafish larvae model was used to evaluate the antioxidant and anti-inflammatory activity of B. serrata extract. According to an in silico study using molecular docking and ADMET, the compounds acetyl-11-keto-boswellic and 11-keto-beta-boswellic acid present in the extract had higher binding affinity for the inflammatory specific receptor, and it is predicted to be an orally active molecule. In both in-vitro L6 cells and in-vivo zebrafish larvae, 160µg/mL concentration of extract caused a high rate of lethality. The extract was found to have a protective effect against LPS-induced inflammation at concentrations ranged between 10 and 80µg/mL. In zebrafish larvae, 80µg/mL of treatment significantly lowered the level of intracellular ROS, apoptosis, lipid peroxidation, and nitric oxide. Similarly, zebrafish larvae treated with B. serrata extract (80µg/mL) showed an increased anti-inflammatory activity by lowering inflammatory specific gene expression (iNOS, TNF-α, COX-2, and IL-1). Overall, our findings suggest that B. serrata can act as a potent redox scavenger against LPS-induced inflammation in zebrafish larvae and an inhibitor of specific inflammatory genes.