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

Olubukola Titilope Oyebode,Olamilekan Salami,Gerhard Prinsloo,Ifeanyi Obi,Olusola Bodede,Olufunso Olabode Olorunsogo,John Oludele Olanlokun

doi:10.1007/s10787-021-00876-x

Olubukola Titilope Oyebode, Olamilekan Salami + Show 5 more

Open Access

https://doi.org/10.1007/s10787-021-00876-x

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Abstract

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 (3days) 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 100mg/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 200mg/kg bw by 71% and 88%, respectively, but only at 100mg/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.

Highlights

The etiology of many diseases stems from inflammation
This study reveals that terpene-rich dichloromethane fraction (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
In order to determine the dose of LPS suitable for induction of inflammation in the mice strain, intraperitoneal administration of two doses (0.5, 1.0 mg/kg) of LPS was tested alongside a control group that received normal saline alone

Summary

Introduction

The etiology of many diseases stems from inflammation. This constitutes a global health concern (Glass et al, 2010; Furman et al, 2019).inflammation regulates defense against infection and promotes repair to prevent further tissue damage, persistent inflammatory process usually drives the onset of a number of disorders arising from various cellular alterations and metabolic interactions that eventually sustain and worsen tissue damage (Medzhitov, 2008; Chen et al, 2017Recent scientific findings reveal that mitochondria are involved in the regulation of innate immunity and are drivers of inflammatory responses (Mohanty et al, 2019; Missiroli et al, 2020). The etiology of many diseases stems from inflammation. This constitutes a global health concern (Glass et al, 2010; Furman et al, 2019).inflammation regulates defense against infection and promotes repair to prevent further tissue damage, persistent inflammatory process usually drives the onset of a number of disorders arising from various cellular alterations and metabolic interactions that eventually sustain and worsen tissue damage The mitochondrial permeability Transition (mPT) pore opening has been shown to occur in many disease conditions including inflammation (Crompton, 1999; Crouser et al, 2004; Oyebode et al, 2019). Several medicinal plants have exhibited modulatory effects on the mPT pore under different conditions (Oyebode et al, 2017; Olanlokun et al, 2018; Olowofolahan et al, 2020)

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