Effect of Aegle marmelos leaf extract on N-methyl N-nitrosourea-induced hepatocarcinogensis in Balb/c mice

Abstract

Context and objective: Tobacco smoke and nitrostable foods containing N-methyl N-nitrosourea (MNU) are among the primary causes of liver cancer. To substantiate the beneficial claims ascribed to Aegle marmelos (L.) Corrêa (Rutaceae), the hepatoprotective potential of its leaf extract was studied using an MNU-induced hepatocarcinogenesis model in Balb/c mice. Materials and methods: After dose selection, 40 mice were randomly assigned to 4 groups: I (control), II (intraperitoneally (i.p.) primed with 50 mg/kg MNU), III (100 mg/kg A. marmelos hydroalcoholic extract (HEAM) i.p.) and IV (MNU + HEAM, i.p.). Inflammatory (IL-1β, IL-6), anti-inflammatory (IL-4) cytokine expression, apoptosis (Bcl-2) and tumor-related (p53, c-jun) genes were assessed at mRNA level. HEAM effects on hematological parameters were examined. Results and discussion: HEAM treatment decreased IL-1β, IL-6, Bcl-2 and c-jun respectively expressions by 90, 25, 53 and 30%, respectively. p53 and IL-4 expression was up-regulated by 1.5- and 2-fold. MNU decreased hemoglobin concentration (25%), lymphocyte count (42%) and increased leukocyte (100%), platelet (4-fold), neutrophil (43%), monocyte (10-fold) and eosinophil (10-fold) counts in Group II mice while HEAM modulated the same parameters by -7%, -21%, +24%, +3-fold, +12%, +3-fold and +4-fold, respectively, in MNU-induced mice compared to control. HEAM protective effect was confirmed by Raman spectroscopy where the MNU-induced peak at 1252 cm-1 was normalized. DNA fragmentation data suggest apoptosis as one of the protective mechanisms of HEAM. Conclusion: The hepatoprotective, anti-carcinogenic and immunomodulatory effects of A. marmelos extract indicate potential beneficial effects in cancer therapy. © 2013 Informa Healthcare USA, Inc. All rights reserved.