In-vivo anticancer activity of combined ethanolic extract of Annona muricata and Rauvolfia vomitoria (AR) in N-Nitroso-N-methylurea (NMU) induced Swiss albino mice
Abstract
Annona muricata and Rauvolfia vomitoria have been combined traditionally to manage and cure many malady in southwestern Nigeria. This study sought to investigate chemotherapeutic anticancer potential of diherbal preparation Annona muricata and Rauvolfia vomitoria (AR) against N-nitroso-N-methylurea (NMU) induced mammary carcinogenesis in mice. Twenty-five female mice (17 -20 g) were divided into five groups of five animals. Group A received distilled water. Groups B, C and D received cisplatin, 50 mg kg-1 and 100 mg kg-1 of the herbal preparation 24 hours after NMU administration respectively, while group E served as tumour placebo. Mice were treated for 12 weeks, and sacrificed via jugular puncture to harvest blood, breast, liver, heart, lungs and kidneys for analysis. Haematology revealed dose-dependently increased haemoglobin, PCV, RBC and MCV in treated mice. Antioxidant expression was observed in treated mice. Histology of breast of treated mice were conserved. Alterations like, mononuclear inflammatory cells admixed with tumour-like single cells, hyperplastic basophilic and neoplastic nuclei were observed in tumour placebo. Internal organs of treated mice did not show alteration, however, tumour placebo revealed perivascular mononuclear cuffing, blood vessel congestion, loss of alveoli sac, hyperplastic basophilic nuclei, glomerular infiltrate and renal haemorrhage. Biochemical analytes did not show any significant difference, also breast of treated mice possessed high concentration of salicylic acid. Increased WBC differentials suggest potential of AR in mitigating NMU. Enhanced status of antioxidant in treated mice evident in decreased MDA, SOD and CAT and increased level of GSH level, ensured decline in lipid peroxidation, thereby conferring AR its anticancer potency via apoptotic induction or neovascularization inhibition. ALP and ALB decrease, in treatment suggest that AR is hepatoprotective. Insignificant level of AST, ALT, protein and LDH connotes that AR is not hepatotoxic. Absence of alterations in treated mice portends AR as antitumorigenic, possibly due to synergy exhibited by bullatacin, annonacin, annomuricin, salicylic acid, sapentine and alstonine in AR.