title: Active chemical fractions of stem bark extract of Khaya grandifoliola C.DC and Entada africana Guill. et Perr. synergistically protect primary rat hepatocytes against paracetamol-induced damage.
abstract: BACKGROUND
  Khaya grandifoliola (Meliaceae) and Entada africana (Fabaceae) are traditionally used in Bamun (a western tribe of Cameroon) traditional medicine for the treatment of liver related diseases. In this study, the synergistic hepatoprotective effect of respective active fractions of the plants were investigated against paracetamol-induced toxicity in primary cultures of rat hepatocytes.
  
  
  METHODS
  Paracetamol conferred hepatocyte toxicity, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) activities, malondialdehyde (MDA) and glutathione (GSH) content assays. The crude extracts were fractionated by flash chromatography and fractions were tested for hepato-(protective and curative) activities. The most active fractions of both plants were tested individually, and in combination based on their respective half effective concentration (EC50).
  
  
  RESULTS
  The methylene chloride/methanol fractions of K. grandifoliola (75:25 v/v) (KgF25) and E. africana (90:10 v/v) (EaF10) were found to be the most hepato-protective with EC50 values of 10.30 ± 1.66 μg/ml and 13.47 ± 2.06 μg/ml respectively, comparable with that of silymarin (13.71 ± 3.87 μg/ml). These fractions and their combination significantly (P <0.05) improved cell viability, inhibited ALT leakage and MDA formation, and restored cellular CAT, SOD activities and GSH content. The combination was more effective in restoring biochemical parameters with coefficients of drugs interaction (CDI) less than 1.
  
  
  CONCLUSIONS
  These findings demonstrate that the active fractions have synergistic action in the protection of rat hepatocytes against paracetamol-induced damage and suggest that their hepatoprotective properties may be maximized by using them in combination.
authors.affiliation: Department of Biochemistry, Laboratory of Pharmacology and Toxicology, Faculty of Science, University of Yaoundé 1, POBox 812, Yaoundé, Cameroon. njayou@yahoo.com.
authors.forename: Frédéric Nico
authors.initials: FN
authors.lastname: Njayou
authors.affiliation: Department of Biochemistry, Laboratory of Pharmacology and Toxicology, Faculty of Science, University of Yaoundé 1, POBox 812, Yaoundé, Cameroon.
authors.forename: Arnaud Fondjo
authors.initials: AF
authors.lastname: Kouam
authors.affiliation: Department of Biochemistry, Laboratory of Pharmacology and Toxicology, Faculty of Science, University of Yaoundé 1, POBox 812, Yaoundé, Cameroon.
authors.forename: Brice Fredy Nemg
authors.initials: BF
authors.lastname: Simo
authors.affiliation: Department of Biochemistry, Laboratory of Pharmacology and Toxicology, Faculty of Science, University of Yaoundé 1, POBox 812, Yaoundé, Cameroon.
authors.forename: Angèle Nkouatchoua
authors.initials: AN
authors.lastname: Tchana
authors.affiliation: Department of Biochemistry, Laboratory of Pharmacology and Toxicology, Faculty of Science, University of Yaoundé 1, POBox 812, Yaoundé, Cameroon.
authors.forename: Paul Fewou
authors.initials: PF
authors.lastname: Moundipa
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D007887:Fabaceae / Q000737:chemistry*; D022781:Hepatocytes / Q000187:drug effects*; D029582:Meliaceae / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: D010936:Plant Extracts; D020011:Protective Agents; D000082:Acetaminophen
keywords: Active fractions; E. africana; Hepatoprotection; K. grandifoliola; Paracetamol; Primary rat hepatocytes; Synergy