title: Effect of Aegle marmelos leaf extract on N-methyl N-nitrosourea-induced hepatocarcinogensis in Balb/c mice.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  The hepatoprotective, anti-carcinogenic and immunomodulatory effects of A. marmelos extract indicate potential beneficial effects in cancer therapy.
authors.affiliation: School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Verma
authors.forename: Theeshan
authors.initials: T
authors.lastname: Bahorun
authors.forename: Ranjan Kumar
authors.initials: RK
authors.lastname: Singh
authors.forename: Okezie I
authors.initials: OI
authors.lastname: Aruoma
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
mesh_terms: D045471:Aegle / Q000737:chemistry; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008770:Methylnitrosourea; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D010946:Plants, Medicinal; D013997:Time Factors
chemical_list: D016588:Anticarcinogenic Agents; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D007155:Immunologic Factors; D018836:Inflammation Mediators; D010936:Plant Extracts; D008770:Methylnitrosourea