title: Isolating the metabolic pathways involved in the hepatoprotective effect of Muntingia calabura against CCl4-induced liver injury using LC/MS Q-TOF.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia.
authors: M S
authors: MS
authors: Rofiee
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia.
authors: M I M
authors: MI
authors: Yusof
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia.
authors: E E
authors: EE
authors: Abdul Hisam
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia.
authors: Z
authors: Z
authors: Bannur
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia; Department of Biomedical Science, Faculty of Medicine and Health Sciences,Universiti Putra Malaysia UPM, 43400 Serdang, Selangor, Malaysia.
authors: Z A
authors: ZA
authors: Zakaria
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia; Department of Biomedical Science, Faculty of Medicine and Health Sciences,Universiti Putra Malaysia UPM, 43400 Serdang, Selangor, Malaysia.
authors: M N
authors: MN
authors: Somchit
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia; Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia. Electronic address: tehlaykek@puncakalam.uitm.edu.my.
authors: L K
authors: LK
authors: Teh
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia; Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia. Electronic address: zakisalleh@puncakalam.uitm.edu.my.
authors: M Z
authors: MZ
authors: Salleh
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D045467:Elaeocarpaceae / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D029646:Tiliaceae / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D010936:Plant Extracts; D020011:Protective Agents; D002251:Carbon Tetrachloride
keywords: CCl(4); Hepatoprotective; LC/MS Q-TOF; Metabolomics; Muntingia calabura