TY - JOUR T1 - Antimutagenicity, antioxidant activity and cytotoxicity of n-tetracosanol, eiocosanoic acid and arjunolic acid isolated from Combretum microphyllum (Combretaceae) JF - BMC Compl.Alternat.Med. Y1 - 2017 A1 - Makhafola,T.J. A1 - Elgorashi,E.E. A1 - McGaw,L.J. A1 - Awouafack,M.D. A1 - Luc Verschaeve A1 - Eloff,J.N. KW - acid KW - Activity KW - ALL KW - an KW - Antimutagenicity KW - Antioxidant activity KW - Arjunolic acid KW - AS KW - at KW - cancer KW - chronic KW - Combretum microphyllum KW - cytotoxicity KW - Development KW - disease KW - Diseases KW - effect KW - effects KW - Eicosanoic acid KW - exposure KW - Follow KW - Hepatocytes KW - Human KW - investigation KW - LED KW - medicinal plant KW - methanol extract KW - method KW - methods KW - Mutagens KW - Mutation KW - n-Tetracosanol KW - ON KW - plant KW - Plant Extracts KW - Plants KW - PROCESSES KW - result KW - results KW - S KW - Salmonella KW - Salmonella typhimurium KW - study KW - Test KW - toxicity KW - values AB - Background: Mutations play a major role in the pathogenesis and development ofseveral chronic degenerative diseases including cancer. It follows, therefore thatantimutagenic compound may inhibit the pathological process resulting from exposureto mutagens. Investigation of the antimutagenic potential of traditional medicinal plantsand compounds isolated from plant extracts provides one of the tools that can be usedin the identification of compounds with potential cancer chemopreventive properties.The aim of this study was to isolate and characterise the compounds responsible forthe antimutagenic potential of Combretum microphyllum.Methods: The methanol extract of C. microphyllum was evaluated for antimutagenicityin the Ames/microsome assay using Salmonella typhimurium TA98. TA100 and TA102.Solvent-solvent fractionation was used to partition the extracts and following theprinciple of bioassay-guided fractionation, three compounds were isolated. The threecompounds were evaluated for their antimutagenic activity in the Ames test usingSalmonella typhimurium TA98, TA100 and TA102. Furthermore, the isolatedcompounds were assessed for their potential antioxidant activity using the quantitative2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging method and theircytotoxic effects were evaluated in the MTT assay using human hepatocytes.Results: A bioassay-guided fractionation of the crude extracts led to the isolation ofthree compounds; n-tetracosanol, eicosanoic acid and arjunolic acid. Arjunolic acidwas the most active in all three tested strains with percentage antimutagenicity of up to41.92 ± 9.59%, 35.84 ± 1.45% and 43.78 ± 0.18% in S. typhimurium TA98, TA100 andTA102 respectively at the highest concentration tested, followed by eicosanoic acidand lastly n-tetracosanol. The antioxidant activity of the compounds were determinedusing the quantitative 2,2 diphenyl-1-picryhydrazyl (DPPH)-free radical scavengingmethod. Only arjunolic acid had pronounced antioxidant activity (measured as DPPHfreescavenging activity) with an EC50 value of 0.51 ìg/ml. The cytotoxicity of theisolated compounds were determined in the MTT assay using human hepatocytes. Thecompounds had low toxicity at the highest concentration tested with LC50 values >200ìg/ml for n-tetracosanol and eicosanoic acid and 106.39 ìg/ml for arjunolic acid.Conclusions: Based on findings from this study, compounds in leaf extracts of C.microphyllum protected against 4-NQO and MMC induced mutations as evident in theAmes test. The antimutagenic activity of arjunolic acid may, at least in part, beattributed to its antioxidant activity resulting in the detoxification of reactive oxygenspecies produced during mutagenesis. VL - submitted U1 - 2673 ER -