This study aims to evaluate the preventive effects
of anthocyanins extracts (MAEs) from mulberry
variety PR-01 against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in rats. It was found that 150 mg·kg-1 MAEs treatment significantly reduced the NDEA-induced
hepatic nodules incidence and hepatocellular carcinoma incidence by 58.30% and
41.70% compared to the model group. Meanwhile, MAEs significantly restored the
elevated the liver function enzymes, inhibited the tumor necrosis factor alpha
and interleukin-6 levels, elevated the serum interleukin-10 and interferon-γand
increased hepatic glutathione-S-transferase and UDP-glucuronosyltransferase 2B1 enzyme activity. Moreover, 150 mg·kg-1 MAEs supplement enhanced glutathione content and
the activities of superoxide dismutase, catalase, glutathione peroxidase
activities but reduced the malondialdehyde and thiobarbituric acid-reactive
substances content by 37.90% and 44.52%. Furthermore, MAEs pretreatment maintained
nuclear factor erythroid 2-related factor 2 (Nrf2),
Kelch-like ECH-associated protein 1, heme oxygenase-1, and NAD(P)H: quinine
oxidoreductase1 stimulation and inhibited the expression of TNF-α, nuclear factor-kappaB (NF-κB), and cyclooxygenase-2 (COX-2), indicating
that MAEs exhibit effectively prevention effects against liver cancer via
decreased lipid peroxidation, induced Nrf2-mediated antioxidant enzymes and
attenuating the inflammatory mediators COX-2 through NF-κB pathway. Thus, MAEs of mulberry variety
Chen, Y.J., Wallig, M.A. and Jeffery, E.H. (2016) Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet. Journal of Nutrition, 146, 542-550.
Huang, H.P., Ou, T.T. and Wang, C.J. (2013) Mulberry (Sang Shen Zi) and Its Bioactive Compounds, the Chemoprevention Effects and Molecular Mechanisms in Vitro and in Vivo. Journal of Traditional and Complementary Medicine, 3, 7-15.
Herr, I. and Buchler, M.W. (2010) Dietary Constituents of Broccoli and Other Cruciferous Vegetables: Implications for Prevention and Therapy of Cancer. Cancer Treatment Reviews, 36, 377-383. https://doi.org/10.1016/j.ctrv.2010.01.002
Liu, H., Yang, J., Huang, S.W., Liu, R.J., He, Y.J., Zheng, D.D. and Liu, C.H. (2017) Mulberry Crude Extracts Induce Nrf2 Activation and Expression of Detoxifying Enzymes in Rat Liver: Implication for Its Protection against NP-Induced Toxic Effects. Journal of Functional Foods, 32, 367-374.
Hassimotto, N.M., Moreira, V., do Nascimento, N.G., Souto, P.C., Teixeira, C. and Lajolo, F.M. (2013) Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside. BioMed Research International, 146716-146710.
Gopalakrishnan, R., Sundaram, J., Sattu, K., Pandi, A. and Thiruvengadam, D. (2013) Dietary Supplementation of Silymarin Is Associated with Decreased Cell Proliferation, Increased Apoptosis, and Activation of Detoxification System in Hepatocellular Carcinoma. Molecular and Cellular Biochemistry, 377, 163-176.
Khoo, H.E., Azlan, A., Tang, S.T. and Lim, S.M. (2017) Anthocyanidins and Anthocyanins: Colored Pigments as Food, Pharmaceutical Ingredients, and the Potential Health Benefits. Food & Nutrition Research, 61, 1361779.
Li, L., Wang, L., Wu, Z., Yao, L., Wu, Y., Huang, L., Liu, K., Zhou, X. and Gou, D. (2014) Anthocyanin-Rich Fractions from Red Raspberries Attenuate Inflammation in Both RAW264.7 Macrophages and a Mouse Model of Colitis. Scientific Reports, 4, 6234. https://doi.org/10.1038/srep06234
Reis, J.F., Monteiro, V.V., de Souza Gomes, R., do Carmo, M.M., da Costa, G.V., Ribera, P.C. and Monteiro, M.C. (2016) Action Mechanism and Cardiovascular Effect of Anthocyanins: A Systematic Review of Animal and Human Studies. Journal of Translational Medicine, 14, 315. https://doi.org/10.1186/s12967-016-1076-5
Azzini, E., Giacometti, J. and Russo, G.L. (2017) Antiobesity Effects of Anthocyanins in Preclinical and Clinical Studies. Oxidative Medicine and Cellular Longevity, 2740364-2740374. https://doi.org/10.1155/2017/2740364
Kujawska, M., Ewertowska, M., Adamska, T. and Sadowski, C. (2014) Antioxidant Effect of Lycopene-Enriched Tomato Paste on N-Nitrosodiethylamine-Induced Oxidative Stress in Rats. Journal of Physiology and Biochemistry, 70, 981-990.
Yan, F., Chen, Y., Azat, R. and Zheng, X. (2017) Mulberry Anthocyanin Extract Ameliorates Oxidative Damage in HepG2 Cells and Prolongs the Lifespan of Caenorhabditis elegans through MAPK and Nrf2 Pathways. Oxidative Medicine and Cellular Longevity, 7956158-7956170.
Cheng, Z.X., Xu, M., Yang, Z.J., Chen, X.W. and Zheng, J.G. (2016) A Preliminary Report of Excellent Crop Germplasm with Rich Functional Ingredients. Fujian Agricultural Science and Technology, 7, 83-84.
Zou, T.B., Wang, M., Gan, R.Y. and Ling, W.H. (2011) Optimization of Ultrasound-Assisted Extraction of Anthocyanins from Mulberry, Using Response Surface Methodology. International Journal of Molecular Sciences, 12, 3006-3017.
Du, Q., Zheng, J. and Xu, Y. (2008) Composition of Anthocyanins in Mulberry and Their Antioxidant Activity. Journal of Food Composition and Analysis, 21, 390-395.
Huang, H.P., Chang, Y.C., Wu, C.H., Hung, C.N. and Wang, C.J. (2011) Anthocyanin-Rich Mulberry Extract Inhibit the Gastric Cancer Cell Growth in Vitro and Xenograft Mice by Inducing Signals of p38/p53 and c-Jun. Food Chemistry, 129, 1703-1709. https://doi.org/10.1016/j.foodchem.2011.06.035
Sarikaphuti, A., Nararatwanchai, T., Hashiguchi, T., Ito, T., Thaworanunta, S., Kikuchi, K., Oyama, Y., Maruyama, I. and Tancharoen, S. (2013) Preventive Effects of Morus alba L. Anthocyanins on Diabetes in Zucker Diabetic Fatty Rats. Experimental and Therapeutic Medicine, 6, 689-695.
Jiang, W., Gao, M., Sun, S., Bi, A., Xin, Y., Han, X., Wang, L., Yin, Z. and Luo, L. (2012) Protective Effect of L-Theanine on Carbon Tetrachloride-Induced Acute Liver Injury in Mice. Biochemical and Biophysical Research Communications, 422, 344-350. https://doi.org/10.1016/j.bbrc.2012.05.022
Tang, C.C., Huang, H.P., Lee, Y.J., Tang, Y.H. and Wang, C.J. (2013) Hepatoprotective Effect of Mulberry Water Extracts on Ethanol-Induced Liver Injury via Anti-Inflammation and Inhibition of Lipogenesis in C57BL/6J Mice. Food and Chemical Toxicology, 62, 786-796. https://doi.org/10.1016/j.fct.2013.10.011
Latief, U., Husain, H., Mukherjee, D. and Ahmad, R. (2016) Hepatoprotective Efficacy of Gallic Acid during Nitrosodiethylamine-Induced Liver Inflammation in Wistar Rats. The Journal of Basic & Applied Zoology, 76, 31-41.
El Mesallamy, H.O., Metwally, N.S., Soliman, M.S., Ahmed, K.A. and Abdel Moaty, M.M. (2011) The Chemopreventive Effect of Ginkgo biloba and Silybum marianum Extracts on Hepatocarcinogenesis in Rats. Cancer Cell International, 11, 38.
Vrzal, R., Illes, P. and Dvorak, Z. (2016) Transplant Drugs Affect the Expression of Phase II and Antioxidant Enzymes in Human Carcinoma Cells HepG2 But Not in Primary Cultures of Human Hepatocytes: In Vitro Comparative Study. Pharmacological Reports, 68, 1008-1014. https://doi.org/10.1016/j.pharep.2016.06.001
Husain, H., Latief, U. and Ahmad, R. (2018) Pomegranate Action in Curbing the Incidence of Liver Injury Triggered by Diethylnitrosamine by Declining Oxidative Stress via Nrf2 and NFkappaB Regulation. Scientific Reports, 8, Article No. 8606.
Mukherjee, D. and Ahmad, R. (2015) Dose-Dependent Effect of N’-Nitrosodiethylamine on Hepatic Architecture, RBC Rheology and Polypeptide Repertoire in Wistar Rats. Interdisciplinary Toxicology, 8, 1-7.