Abstract
The use of herbal products and/or their derivatives as an alternative or complementary medicine becomes globally popular. To date, various biological activities have been reported in Morinda citrifolia Linn, especially antioxidants, antimicrobial, anti-inflammatory and antitumor effects. This study aimed to investigate the genotoxicity and DNA repair capacity of the aqueous fruit extract of M. citrifolia (AEMC). Additionally, we checked the mutagenic capacity of AEMC by the comet assay and micronucleus tests in rats. For this, rats (n = 10; 5 males and 5 females) were divided into five groups as: negative control (distilled water); positive control (25 mg/kg of cyclophosphamide, i.p.); and three groups for AEMC (2.5, 5 and 10 mg/kg, i.p.). The results suggest that, the AEMC induced genotoxicity in white blood cells, but a DNA repair capacity was also observed after 72 h of AEMC exposure. AEMC also showed cytotoxicity and mutagenicity in liver and kidney cells of rats at 5 and 10 mg/kg doses. In conclusion, AEMC exhibited a dose-dependent cytotoxicity, genotoxicity and mutagenicity along with a time-dependent DNA repair capacity in rats. Further studies are necessary regarding the safe use of this medicinal plant for human consumption.
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Alonso-Castro AJ, Domínguez F, García-Carrancá A (2013) Rutin exerts antitumor effects on nude mice bearing SW480 tumor. Arch Med Res 44:346–351
Becker JB, Prendergast BJ, Liang JW (2016) Female rats are not more variable than male rats: a meta-analysis of neuroscience studies. Biol Sex Differ 7:34
Belkaid A, Currie JC, Desgagnés J, Annabi B (2006) The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression. Cancer Cell Int 6:7
Burgess DJ (2013) Apoptosis: refined and lethal. Nat Rev Cancer 13:79
Burgos-Morón E, Calderón-Montaño JM, Orta ML, Pastor N, Pérez-Guerrero C, Austin C, Mateos S, López-Lázaro M (2012) The coffee constituent chlorogenic acid induces cellular DNA damage and formation of topoisomerase I- and II-DNA complexes in cells. J Agric Food Chem 60:7384–7391
Clafshenkel WP, King TL, Kotlarczyk MP, Cline JM, Foster WG, Davis VL, Witt-Enderby PA (2012) Morinda citrifolia (Noni) juice augments mammary gland differentiation and reduces mammary tumor growth in mice expressing the unactivated c-erb b2 transgene. Evid Based Complement Altern Med 2012:1–15
Costa BA, Oliveira JMG, Sales PAB, Lira SRS, Silva SMMS, Costa LM, Muratori MCS, Costa APR (2013) Systemic and reproductive toxicity induced by Parkia platycephala ethanolic extract in female Wistar rats. Barz J Pharmacogn 23:920–926
de Araújo KC, Costa EM, Pazini F, Valadares MC, de Oliveira V (2013) Bioconversion of quercetin and rutin and the cytotoxicity activities of the transformed products. Food Chem Toxicol 51:93–96
Downes N, Foster J (2015) Regulatory forum opinion piece: carcinogen risk assessment: the move from screens to science. Toxicol Pathol 43:1064–1073
Furusawa E, Hirazumi A, Story S, Jensen J (2003) Antitumour potential of a polysaccharide-rich substance from the fruit juice of Morinda citrifolia (Noni) on sarcoma 180 ascites tumour in mice. Phytother Res 17:1158–1164
Gonzalez FJ, Yu AM (2006) Cytochrome P450 and xenobiotic receptor humanized mice. Annu Rev Pharmacol Toxicol 46:41–64
Guicciardi ME, Malhi H, Mott JL, Gores GJ (2013) Apoptosis and necrosis in the liver. Compr Physiol 3:977–1010
Guzman A, Garcia C, Marin AP, Proudlock RJ, Fernandez De Henestrosa AR, Ruiz MT, Tortajada A, Lloyd M, Marcos R (2008) Evaluation of the genotoxic potential of three phenyltetrahydropyrinidyl butylazole-derived sigma-receptor ligand candidates. Mutat Res 653:91–98
Han DH, Lee MJ, Kim JH (2006) Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Res 26:3601–3606
Islam MT, Mata AMOF, Aguiar RPS, Paz MFCJ, Alencar MVOB, Melo-Cavalcante AAC (2016) Therapeutic potential of essential oils focusing on diterpens. Phytother Res 30:1420–1444
Islam MT, Streck L, Alencar MVOB, Silva SWC, Machado KC, Machado KC, Júnior ALG, Paz MFCJ, Mata AMOF, Sousa JMC, Junior JSC, Rolim HML, Silva-Junior AA, Melo-Cavalcante AAC (2017) Evaluation of toxic, cytotoxic and genotoxic effects of phytol and its nanoemulsion. Chemosphere 177:93–101
Iyama T, Wilson DM III (2013) DNA repair mechanisms in dividing and non-dividing cells. DNA Repair 12:620–636
Jiang Y, Zhang Y, Wark L, Ortiz E, Lim S, He H, Wang W, Medeiros D, Lin D (2011) Wolfberry water soluble phytochemicals down-regulate ER stress biomarkers and modulate multiple signaling pathways leading to inhibition of proliferation and induction of apoptosis in Jurkat cells. J Nutr Food Sci S2(pii):001
Kasamoto S, Masumori S, Hayashi M (2013) In vivo micronucleus assay in mouse bone marrow and peripheral blood. Methods Mol Biol 1044:179–189
Kato K, Yamamura E, Kawanishi M, Yagi T, Matsuda T, Sugiyama A, Uno Y (2011) Application of the DNA adductome approach to assess the DNA-damaging capability of in vitro micronucleus test-positive compounds. Mutat Res 721:21–26
Kirkim G, Olgun Y, Aktas S, Kiray M, Kolatan E, Altun Z, Erçetin P, Bagriyanik A, Yilmaz O, Ellidokuz H (2015) Is there a gender-related susceptibility for cisplatin ototoxicity? Eur Arch Otorhinolaryngol 272:2755–2763
Kuo YY, Jim WT, Su LC, Chung CJ, Lin CY, Huo C, Tseng JC, Huang SH, Lai CJ, Chen BC, Wang BJ, Chan TM, Lin HP, Chang WS, Chang CR, Chuu CP (2015) Caffeic acid phenethyl ester is a potential therapeutic agent for oral câncer. Int J Mol Sci 16:10748–10766
Luzhna L, Kathiria P, Kovalchuk O (2013) Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond. Front Genet 4:131
Maeda J, Roybal EJ, Brents CA, Uesaka M, Aizawa Y, Kato TA (2014) Natural and glucosyl flavonoids inhibit poly (ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells. Oncol Rep 31:551–556
Mendanha DM, Ferreira HD, Felício LP, Silva EM, Pereira DG, Nunes WB, Carvalho S (2010) Modulatory effect of Byrsonima verbascifolia (Malpighiaceae) against damage induced by doxorubicin in somatic cells of Drosophila melanogaster. Genet Mol Res 9:69–77
Mertens-Talcott SU, Percival SS (2005) Ellagic acid and quercetin interact synergistically with resveratrol in the induction of apoptosis and cause transient cell cycle arrest in human leukemia cells. Cancer Lett 218:141–151
Mok DKW, Chau F (2006) Chemical information of Chinese medicines: a challenge to chemist. Chemom Intell Lab Syst 82:210–217
Moraes GP, Alencar MVOB, Islam MT, Araujo LS, Sobral ALP, Machado KC, Aguiar RPS, Junior ALG, Correa D, Paz MFCJ, Ferreira PMP, Melo-Cavalcante AAC, Ferraz A, Grivicich I, Picada JN (2016) Cytogenotoxic and oxidative status evaluation of Morinda citrifolia. Int Arch Med 9:1–13
Parasuraman S (2011) Toxicological screening. J Pharmacol Pharmacother 2:74–79
Ramalingum N, Mahomoodally MF (2014) The therapeutic potential of medicinal foods. Adv Pharmacol Sci 2014:1–18
Rim KT, Kim SJ (2015) A review on mutagenicity testing for hazard classification of chemicals at work: focusing on in vivo micronucleus test for allyl chloride. Saf Health Work 6:184–191
Rogers FA, Tiwari MK (2013) Triplex-induced DNA damage response. Yale J Biol Med 86:471–478
Singh D, Baghel US, Yadav D, Sharma M, Yadav R (2015) Impact of herbal medicines on conventional drugs: an overview. Asian J Exp Sci 29:15–28
Speit G, Rothfuss A (2012) The comet assay: a sensitive genotoxicity test for the detection of DNA damage and repair. Methods Mol Biol 314:79–90
Suhas S, Ganapathy KS, Gayatri Devi M, Ramesh C (2004) Application of the micronucleus test to exfoliated epithelial cells from the oral cavity of beedi smokers, a high-risk group for oral cancer. Mutat Res 561:15–21
Tavares W (1996) Manual de antibióticos e quimioterápicos anti-infecciosos - introdução ao estudo dos antimicrobianos. Atheneu, Rio de Janeiro, p 792
Torres-Bugarín O, Pacheco-Gutiérrez AG, Vázquez-Valls E, Ramos-Ibarra ML, Torres-Mendoza BM (2014) Micronuclei and nuclear abnormalities in buccal mucosa cells in patients with anorexia and bulimia nervosa. Mutagenesis 29:427–431
Vandghanooni S, Eskandani M (2011) Comet assay: a method to evaluate genotoxicity of nano-drug delivery system. Bioimpacts 1:87–97
Waldman W, Piotrowicz G, Sein Anand J (2013) Hepatoxic effect of a noni juice consumption-a case report. Przegl Lek 70:690–692
Waters MD, Jackson M, Lea I (2010) Characterizing and predicting carcinogenicity and mode of action using conventional and toxicogenomics methods. Mutat Res 705:184–200
Yan Y, Li J, Han J, Hou N, Song Y, Dong L (2015) Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal regulated kinases. Anticancer Drugs 26:540–546
Zhang HM, Zhao L, Li H, Xu H, Chen WW, Tao L (2014) Research progress on the anticarcinogenic actions and mechanisms of ellagic acid. Cancer Biol Med 11:92–100
Acknowledgements
The authors wish to thank the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Piauí (FAPEPI) for the financial support.
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The protocols were approved by the Ethical Committee on Animal Research at NOVAFAPI (Process No. #0039/10) and are in accordance with the national (Colégio Brasileiro de Experimentação Animal—COBEA) and international standard for the care and use of experimental laboratory animals.
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de Moraes, G.P., de Alencar, M.V.O.B., Araújo, L.d. et al. Cytogenotoxic study of aqueous fruit extract of Morinda citrifolia in Wistar albino rats. Orient Pharm Exp Med 19, 311–321 (2019). https://doi.org/10.1007/s13596-019-00358-0
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DOI: https://doi.org/10.1007/s13596-019-00358-0