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Isolating the metabolic pathways involved in the hepatoprotective effect of Muntingia calabura against CCl4-induced liver injury using LC/MS Q-TOF

Rofiee, M.S., Yusof, M.I.M., Abdul Hisam, E.E., Bannur, Z., Zakaria, Z.A., Somchit, M.N., Teh, L.K., Salleh, M.Z.
Journal of ethnopharmacology 2015 v.166 pp. 109-118
Muntingia calabura, acute toxicity, analgesics, animal models, antiseptics, bile acids, biochemical pathways, biomarkers, biosynthesis, blood serum, body weight, dose response, gene expression regulation, hepatoprotective effect, hepatotoxicity, histopathology, liquid chromatography, liver, mass spectrometry, metabolites, metabolomics, parasympatholytics, principal component analysis, rats, therapeutics, traditional medicine, South East Asia
Muntingia calabura L. has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the acute toxicity and the metabolic pathways involved in the hepatoprotective mechanism of M. calabura.CCl4-induced hepatotoxic rat model was developed and a dose dependent effect of M. calabura was conducted. Body weight, food and water consumption were measured every day and rats were sacrificed to collect the serum samples at the end of the 10-days treatment. Liquid chromatography–mass spectrometry quadrapole time of flight (LC/MS-QTOF) combined with principal component analysis (PCA) were used to determine differentially expressed metabolites due to treatment with CCl4 and M. calabura extracts. Metabolomics Pathway Analysis (MetPA) was used for analysis and visualization of pathways involved.Body weight, food and water consumption were significantly decreased and histopathological study revealed steatosis in CCl4-induced rats. PCA score plots show distinct separation in the metabolite profiles of the normal group, CCl4-treated group and extract of M. calabura (MCME) pre-treated groups. Biomarkers network reconstruction using MetPA had identified 2 major pathways which were involved in the protective mechanism of MCME. These include the (i) biosynthesis of the primary bile acid, (ii) metabolism of arachidonic acid.This study has successfully isolated 2 major pathways involved in the hepatoprotecive effect of MCME against CCl4-induced liver injury using the LC/MS Q-TOF metabolomics approach. The involvement of archidonic acid and purine metabolism in hepatoprotection has not been reported previously and may provide new therapeutic targets and/or options for the treatment of liver injury.