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Mangosteen can improve steatohepatitis through modulating inflammatory and autophagy/apoptosis cellinjury: an animal model study
Nonalcoholic fatty liver disease (NAFLD) is characterized by triglycerides deposition in hepatocytes causing their injury and leading to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Mangosteen (MG) is a tropical fruit that contains a lot of bioactive antioxidant, and antiadipogenic compounds. Aim: To investigate the ability of MG to ameliorate NAFLD/NASH and its role in the regulation of apoptosis and autophagy within the injured hepatocytes. A total number of 50 adult male mice were divided into 5 groups: GI were fed with standard diet, GII were fed with high fat diet (HFD), GIII were fed with HFD concomitant with MG by oral gavage for 16 weeks, GIV were fed with HFD for 16 weeks followed by MG for 2 weeks, and GV were fed with HFD for 16 weeks followed by standard diet (SD) for 2 weeks. MG reduced body weight gain, liver weight coefficient, and plasma free fatty acids levels. There was a decrease in lipid accumulation with improved liver function. Most of the histopathological changes observed in NASH were ameliorated. Immunohistochemical results showed that MG increased autophagy process and suppressed hepatocyte apoptosis. There was a significant decrease in CD68 positive macrophages and a significant decrease in αSMA expression. MG exerts effects by regulating hepatic lipid homeostasis, inflammation, apoptosis, and autophagy. Therefore, it could be a new approach to a dietary based method that suspends the onset and development of steatohepatitis, liver cirrhosis and HCC risk by the prevention and management of NAFLD//NASH.
Key words: Nonalcoholic fatty liver disease, steatohepatitis, mangosteen, apoptosis, autophagy
E-mail: eman_elmadany yahoo.com
1. Abdelmegeed, M.A., et al., Corrigendum: cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis, Sci. Rep., 2017, vol. 7, p. 42566.
2. Bloomgarden, Z.T., Inflammation and insulin resistance, Diabetes Care, 2003, vol. 26, no. 6, pp. 922–926.
3. Chae, H.S., et al., Mangosteen extract attenuates the metabolic disorders of high-fat-fed mice by activating AMPK, J. Med. Food, 2016, vol. 19, no. 2, pp. 148–154.
4. Chin, Y.W. and Kinghorn, A.D., Structural characterization, biological effects, and synthetic studies on xanthones from mangosteen (Garcinia mangostana), a popular botanical dietary supplement, Mini Rev. Org. Chem., 2008, vol. 5, no. 4, pp. 355–364.
5. Grundy, S.M., Obesity, metabolic syndrome, and cardiovascular disease, J. Clin. Endocrinol. Metab., 2004, vol. 89, no. 6, pp. 2595–2600.
6. Hansen, H.H., et al., Mouse models of nonalcoholic steatohepatitis in preclinical drug development, Drug Discov. Today, 2017, vol. 22, no. 11, pp. 1707–1718.
7. Inami, Y., et al., Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression, Biochem. Biophys. Res. Commun., 2011, vol. 412, no. 4, pp. 618–625.
8. Jordan, T., et al., Comparison of bleaching protocols utilizing hematoxylin and eosin stain and immunohistochemical proliferation marker MCM3 in pigmented melanomas, J. Histotechnol., 2019, pp. 1–6.
9. Karim, N. and Rahman, A., Mangosteen vinegar rind from Garcinia mangostana prevents high-fat diet and streptozotocin-induced type II diabetes nephropathy and apoptosis, Food Sci., 2019, vol. 84, no. 5, pp. 1208–1215.
10. Karim, N., Jeenduang, N., and Tangpong, J., Renoprotective effects of xanthone derivatives from Garcinia mangostana against high fat diet and streptozotocin-induced type II diabetes in mice, Walailak J. Sci. Technol., 2018, vol. 15, no. 2, pp. 107–116.
11. Kim, H.M., et al., α-Mangostin ameliorates hepatic steatosis and insulin resistance by inhibition C-C chemokine receptor 2, PLoS One, 2017, vol. 12 (6), e0179204.
12. Markowicz, J., et al., Antitumor and anti-nematode activities of alpha-mangostin, Eur. J. Pharmacol., 2019, vol. 863, p. 172678.
13. Moreira, R.K., Hepatic stellate cells and liver fibrosis, Arch. Pathol. Lab. Med., 2007, vol. 131, no. 11, pp. 1728–1734.
14. Neuman, M.G., Cohen, L.B., and Nanau, R.M., Biomarkers in nonalcoholic fatty liver disease, Can. J. Gastroenterol. Hepatol., 2014, vol. 28, no. 11, pp. 607–618.
15. Ovalle-Magallanes, B., Eugenio-Perez, D., and Pedraza-Chaverri, J., Medicinal properties of mangosteen (Garcinia mangostana L.): a comprehensive update, Food Chem. Toxicol., 2017, vol. 109 (Pt 1), pp. 102–122.
16. Ramadori, G. and Saile, B., Portal tract fibrogenesis in the liver, Lab. Invest., 2004, vol. 84, no. 2, p. 153.
17. Seki, S., et al., In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases, J. Hepatol., 2002, vol. 37, no. 1, pp. 56–62.
18. Shen, Q., et al., Adipocyte reporter assays: application for identification of anti-inflammatory and antioxidant properties of mangosteen xanthones, Mol. Nutr. Food Res., 2014, vol. 58, no. 2, pp. 239–247.
19. Sinha, R.A., et al., Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy, J. Clin. Invest., 2012, vol. 122, no. 7, pp. 2428–2438.
20. Thapa, M., et al., Liver fibrosis occurs through dysregulation of MyD88-dependent innate B-cell activity, Hepatology, 2015, vol. 61, no. 6, pp. 2067–2079.
21. Tsai, S.Y., et al., Alpha-mangostin from mangosteen (Garcinia mangostana Linn.) pericarp extract reduces high fat-diet induced hepatic steatosis in rats by regulating mitochondria function and apoptosis, Nutr. Metab. (Lond.), 2016, vol. 13, p. 88.
22. Vanheule, E., et al., An intravital microscopic study of the hepatic microcirculation in cirrhotic mice models: relationship between fibrosis and angiogenesis, Int. J. Exp. Pathol., 2008, vol. 89, no. 6, pp. 419–432.
23. Vernon, G., Baranova, A., and Younossi, Z.M., Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults, Aliment. Pharmacol. Ther., 2011, vol. 34, no. 3, pp. 274–285.
24. Wanninger, J., et al., Lipid accumulation impairs adiponectin-mediated induction of activin A by increasing TGFbeta in primary human hepatocytes, Biochim. Biophys. Acta—Mol. Cell Biol. Lipids, 2011, vol. 1811, no. 10, pp. 626–633.
25. Weiskirchen, R. and Tacke, F., Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology, Hepatobil. Surg. Nutr., 2014, vol. 3, no. 6, p. 344.
26. Wudtiwai, B., Pitchakarn, P., and Banjerdpongchai, R., Alpha-mangostin, an active compound in Garcinia mangostana, abrogates anoikis-resistance in human hepatocellular carcinoma cells, Toxicol. In Vitro, 2018, vol. 53, pp. 222–232.
27. Yang, L., et al., Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance, Cell Metab., 2010, vol. 11, no. 6, pp. 467–478.
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