Terpene‑rich fractions of Ficus mucoso (Welw) modulate lipopolysaccharide‑induced infammatory mediators and aberrant permeability of the inner mitochondrial membrane in murine animal model

Ficus mucoso is traditionally used to treat bronchial infections. This study compared the efficacy of terpene-rich fractions of F. mucoso root bark on lipopolysaccharide(LPS)-induced inflammation, liver mitochondrial permeability transition (mPT), 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 standard procedures. To induce systemic inflammation, a single intraperitoneal injection of 1mgLPS/kgbw was given to mice. Spectrophotometric techniques were used to evaluate the effects of the oral administration of TRDF and TREF (3 days) on levels of pro-inflammatory mediators (TNF-α, IL-1β, IL-6) using ELSA techniques as well as antioxidant indices in normal and LPS-treated mice. The mPT pore opening, mitochondrial ATPase activity and lipid peroxidation were monitored spectrophotometrically. Our results revealed that treatment with LPS caused significant elevation in serum cytokine levels while administration of 50 and 100 mg/kg TRDF and TREF significantly reduced elevated serum levels of cytokines (TNF-α, IL-1β, IL-6) in LPS-challenged mice. In addition, activitities of superoxide dismutase, catalase and liver marker enzymes (ALT and AST) as well as levels of mitochondrial lipid peroxides were significantly reduced in mice treated with TRDF and TREF relative to LPS-fed mice. 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. 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.