Terpene-rich Fractions of Ficus Mucoso (Welw) Modulate Lipopolysaccharide-induced Inflammatory Mediators and Aberrant Permeability of the Inner Mitochondrial Membrane in Murine Animal Model

Abstract

Ficus mucoso is traditionally used to treat various infections. This study compared the efficacy of terpene-rich fractions of F. mucoso root bark on LPS-induced inflammation, liver mitochondrial permeability transition (mPT) pore, an index of mitochondrial health, and associated pathological alterations. Terpene-Rich fractions of Dichloromethane (TRDF) and Ethylacetate fractions of F. mucoso (TREF) were obtained according to the method described by Ferguson (1956). A single intraperitoneal injection of 1 mg/kg lipopolysaccharide (LPS) were given to mice to induce systemic inflammation for 72hrs. Evaluation of the effects of the TRDF and TREF on levels of pro-inflammatory mediators (TNF-α, IL-1β, IL-6) and antioxidant indices against LPS-induced hepatic damage were carried out. Mitochondrial swelling was monitored spectrophotometrically as well as mitochondrial ATPase activity and lipid peroxidation. This study reveals that TRDF and TREF possess anti-inflammatory potentials which is related to reduction in levels of pro-inflammatory cytokines, restoration of antioxidant status, reduction in levels of liver marker enzymes as well as associated pathological injury. Furthermore, LPS caused induction of opening of the liver mPT pore which was significantly inhibited by TRDF at 100 and 200 mg/kg bw by 71% and 88% respectively, but only at 100 mg/kg TREF. Furthermore, mitochondrial ATPase activity was inhibited largely by TRDF. The UPLC-ESI-MS analysis revealed the presence of terpenoid derivatives and a few aromatic metabolites in TRDF. The terpene dominance of TRDF metabolites was further justified on the 1H NMR fingerprint.Overall, TRDF is more effective as a cocktail of anti-inflammatory compounds than TREF against LPS-induced acute systemic inflammation.