Phytoestrogens and NAFLD: Possible Mechanisms of Action

Author(s): Hui Li, Erna Jia, Yu Hong, Yanzhen Chen, Jian Jiao*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 20 , Issue 7 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Nonalcoholic Fatty Liver Disease (NAFLD) includes a variety of changes including nonalcoholic fatty liver, cirrhosis and Hepatocellular Carcinoma (HCC), which are associated with metabolic disorders and cardiovascular diseases. The pathogenesis of NAFLD is complex and multifactorial. Many studies have shown that estrogen has a protective effect on premenopausal women with metabolic disorders and non-alcoholic fatty liver disease. Estrogen supplements may, at least in theory, prevent the development and progression of NAFLD. Phytoestrogen is extracted from plants, especially legumes, whose molecular structure and biological activity are similar to those of mammals estrogen, therefore it could replace the role of estrogen and prevent the occurrence of adverse reactions to estrogen. In this article, we review the published literature related to phytoestrogens and NAFLD as well as suggest the possible mechanisms that may underlie the association between phytoestrogens and NAFLD.

Keywords: Phytoestrogens, NAFLD, antioxidant, signaling pathway, liver disease, estrogen.

[1]
Yildiz, F. Phytoestrogens in Functional Foods. CRC Press; Taylor & Francis Ltd, 2005.
[2]
Slavin, J.L.; Lloyd, B. Health benefits of fruits and vegetables. Adv. Nutr., 2012, 3(4), 506-516.
[3]
Hashimoto, Y.; Hamaguchi, M.; Fukuda, T.; Ohbora, A.; Kojima, T.; Fukui, M. Fatty liver as a risk factor for progression from metabolically healthy to metabolically abnormal in non-overweight individuals. Endocrine, 2017, 57(1), 89-97.
[4]
Ballestri, S.; Nascimbeni, F.; Baldelli, E.; Marrazzo, A.; Romagnoli, D.; Lonardo, A. NAFLD as Sexual Dimorphic Disease: Role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk. Adv. Ther., 2017, 34(6), 1291-1326.
[5]
Gutierrez-Grobe, Y.; Ponciano-Rodríguez, G.; Ramos, M.H.; Uribe, M.; Méndez-Sánchez, N. Prevalence of non-alcoholic fatty liver disease in premenopausal, posmenopausal and polycystic ovary syndrome women. The role of estrogens. Ann. Hepatol., 2010, 9(4), 402-409.
[6]
Bruno, S.; Maisonneuve, P.; Castellana, P.; Rotmensz, N.; Rossi, S.; Maggioni, M.; Persico, M.; Colombo, A.; Monasterolo, F.; Casadei-Giunchi, D.; Desiderio, F.; Stroffolini, T.; Sacchini, V.; Decensi, A.; Veronesi, U. Incidence and risk factors for nonalcoholic steatohepatitis: Prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial. BMJ, 2005, 23, 330(7497), 932.
[7]
McKenzie, J.; Fisher, B.M.; Jaap, A.J.; Stanley, A.; Paterson, K.; Sattar, N. Effects of HRT on liver enzyme levels in women with type 2 diabetes: A randomized placebo-controlled trial. Clin. Endocrinol. (Oxf.), 2006, 65(1), 40-44.
[8]
Hamaguchi, M.; Kojima, T.; Ohbora, A.; Takeda, N.; Fukui, M.; Kato, T. Aging is arisk factor of nonalcoholic fatty liver disease in premenopausal women. World J. Gastroenterol., 2012, 18, 237-243.
[9]
Yang, J.D.; Abdelmalek, M.F.; Pang, H.; Guy, C.D.; Smith, A.D.; Diehl, A.M.; Suzuki, A. Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis. Hepatology, 2014, 59, 1406-1414.
[10]
Yoneda, M.; Thomas, E.; Sumida, Y.; Schiffet, E.R. The influence of menopause on the development of hepatic fibrosis in nonobese women with nonalcoholic fatty liver disease. Hepatology, 2014, 60, 1792.
[11]
Luo, F.; Ishigami, M.; Achiwa, K.; Ishizu, Y.; Kuzuya, T.; Honda, T.; Hayashi, K.; Ishikawa, T.; Katano, Y.; Gotoet, H. Raloxifene ameliorates liver fibrosis of nonalcoholic steatohepatitis induced by choline-deficient high-fat diet in ovariectomized mice. Dig. Dis. Sci., 2015, 60, 2730-2273.
[12]
McKenzie, J.; Fisher, B.M.; Jaap, A.J.; Stanley, A.; Paterson, K.; Sattar, N. Effects of HRT on liver enzyme levels in women with type 2 diabetes: A randomized placebo-controlled trial. Clin. Endocrinol. (Oxf.), 2006, 65, 40-44.
[13]
Clark, J.M.; Brancati, F.L.; Diehl, A.M. Nonalcoholic fatty liver disease. Gastroenterology, 2002, 122, 1649-1657.
[14]
Klair, J.S.; Yang, J.D.; Abdelmalek, M.F.; Guy, C. D.; Gill, R.M.; Yates, K.; Unalp-Arida, A.; Lavine, J.E.; Clark, J.M.; Diehl, A.M.; Suzuki, A. A longer duration of estrogen deficiency increases fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease. Hepatology, 2016, 64, 85-91.
[15]
Yang, J.D.; Abdelmalek, M.F.; Guy, C.D.; Gill, R.M.; Lavine, J.E.; Yates, K.; Klair, J.; Terrault, N.A.; Clark, J.M.; Unalp-Arida, A.; Diehl, A.M.; Suzuki, A. Patient sex, reproductive status, and synthetic hormone use associate with histologic severity of nonalcoholic steatohepatitis. Clin. Gastroenterol. Hepatol., 2017, 15, 127-131.
[16]
Villa, E. Role of estrogen in liver cancer. Womens Health (Lond), 2008, 4, 41-50.
[17]
Yang, D.; Hanna, D.L.; Usher, J.; LoCoco, J.; Chaudhari, P.; Lenz, H-J.; Setiawan, V.W.; El-Khoueiry, A. Impact of sex on the survival of patients with hepatocellular carcinoma: A surveillance, epidemiology, and end results analysis. Cancer, 2014, 120, 3707-3716.
[18]
Jung, J.H.; Kim, H.S. The inhibitory effect of black soybean on hepatic cholesterol accumulation in high cholesterol and high fat diet-induced non-alcoholic fatty liver disease. Food Chem. Toxicol., 2013, 60, 404-412.
[19]
Jeon, S.; Park, Y.J.; Kwon, Y.H. Genistein alleviates the development of nonalcoholic steatohepatitis in ApoE(-/-) mice fed a high-fat diet. Mol. Nutr. Food Res., 2014, 58(4), 830-841.
[20]
Kim, J.H.; Kim, Y.J. Effects of genistein in combination with conjugated estrogens on endometrial hyperplasia and metabolic dysfunction in ovariectomized mice. Endocr. J., 2015, 62(6), 531-542.
[21]
Huang, C.; Qiao, X.; Dong, B. Neonatal exposure to genistein ameliorates high-fat diet-induced non-alcoholic steatohepatitis in rats. Br. J. Nutr., 2011, 106(1), 105-113.
[22]
Kim, M.H.; Park, J.S.; Jung, J.W.; Byun, K.W.; Kang, K.S.; Lee, Y.S. Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism. Int. J. Obes. (Lond)., 2011, 35(8), 1019-1030.
[23]
Panneerselvam, S.; Packirisamy, R.M.; Bobby, Z.; Elizabeth Jacob, S.; Sridhar, M.G. Soy isoflavones (Glycine max) ameliorate hypertriglyceridemia and hepatic steatosis in high fat-fed ovariectomized Wistar rats (an experimental model of postmenopausal obesity). J. Nutr. Biochem., 2016, 38, 57-69.
[24]
Park, H.S.; Hur, H.J.; Kim, S.H.; Park, S.J.; Hong, M.J.; Sung, M.J.; Kwon, D.Y.; Kim, M.S. Biochanin A improves hepatic steatosis and insulin resistance by regulating the hepatic lipid and glucose metabolic pathways in diet-induced obese mice. Mol. Nutr. Food Res., 2016, 60(9), 1944-1955.
[25]
Hess, D.; Igal, R.A. Genistein downregulates de novo lipid synthesis and impairs cell proliferation in human lung cancer cells. Exp. Biol. Med. (Maywood), 2011, 236(6), 707-713.
[26]
Kim, M.H.; Park, J.S.; Jung, J.W.; Byun, K.W.; Kang, K.S.; Lee, Y.S. Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism. Int. J. Obes. (Lond)., 2011, 35(8), 1019-1030.
[27]
Kay, H.Y.; Kim, W.D.; Hwang, S.J.; Choi, H.S.; Gilroy, R.K.; Wan, Y.J.; Kim, S.G. Nrf2 inhibits LXRα-dependent hepatic lipogenesis by competing with FXR for acetylase binding. Antioxid. Redox Signal., 2011, 15(8), 2135-2146.
[28]
Kim, Y.W.; Kim, Y.M.; Yang, Y.M.; Kim, T.H.; Hwang, S.J.; Lee, J.R.; Kim, S.C.; Kim, S.G. Inhibition of SREBP-1c-mediated hepatic steatosis and oxidative stress by sauchinone, an AMPK-activating lignan in Saururus chinensis. Free Radic. Biol. Med., 2010, 48(4), 567-578.
[29]
Panneerselvam, S.; Packirisamy, R.M.; Bobby, Z.; Elizabeth Jacob, S.; Sridhar, M.G. Soy isoflavones (Glycine max) ameliorate hypertriglyceridemia and hepatic steatosis in high fat-fed ovariectomized Wistar rats (an experimental model of postmenopausal obesity). J. Nutr. Biochem., 2016, 38, 57-69.
[30]
Mohamed Salih, S.; Nallasamy, P.; Muniyandi, P.; Periyasami, V. Carani Venkatraman. A Genistein improves liver function and attenuates non-alcoholic fatty liver disease in a rat model of insulin resistance. J. Diabetes, 2009, 1(4), 278-287.
[31]
Jeon, S.; Park, Y.J.; Kwon, Y.H. Genistein alleviates the development of nonalcoholic steatohepatitis in ApoE(-/-) mice fed a high-fat diet. Mol. Nutr. Food Res., 2014, 58(4), 830-841.
[32]
Kim, M.H.; Kang, K.S.; Lee, Y.S. The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease. Br. J. Nutr., 2010, 104(9), 1333-1342.
[33]
Gao, X.; van der Veen, J.N.; Hermansson, M.; Ordoñez, M.; Gomez-Muñoz, A.; Vance, D.E.; Jacobs, R.L. Decreased lipogenesis in white adipose tissue contributes to the resistance to high fat diet-induced obesity in phosphatidylethanolamine N-methyltransferase-deficient mice. Biochim. Biophys. Acta, 2015, 1851(2), 152-162.
[34]
Miller, C.N.; Yang, J.Y.; Avra, T.; Ambati, S.; Della-Fera, M.A.; Rayalam, S.; Baile, C.A. A dietary phytochemical blend prevents liver damage associated with adipose tissuemobilization in ovariectomized rats. Obesity (Silver Spring), 2015, 23(1), 112-119.
[35]
Park, H.S.; Hur, H.J.; Kim, S.H.; Park, S.J.; Hong, M.J.; Sung, M.J.; Kwon, D.Y.; Kim, M.S. Biochanin A improves hepatic steatosis and insulin resistance by regulating the hepatic lipid and glucose metabolic pathways in diet-induced obese mice. Mol. Nutr. Food Res., 2016, 60(9), 1944-1955.
[36]
Jeon, S.; Park, Y.J.; Kwon, Y.H. Genistein alleviates the development of nonalcoholic steatohepatitis in ApoE(-/-) mice fed a high-fat diet. Mol. Nutr. Food Res., 2014, 58(4), 830-841.
[37]
Ji, G.; Yang, Q.; Hao, J.; Guo, L.; Chen, X.; Hu, J.; Leng, L.; Jiang, Z. Anti-inflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanisms. Int. Immunopharmacol., 2011, 11(6), 762-768.
[38]
Park, Y.J.; Jang, Y.M.; Kwon, Y.H. Isoflavones prevent endoplasmic reticulum stress-mediated neuronal degeneration by inhibiting tau hyperphosphorylation in SH-SY5Y cells. J. Med. Food, 2009, 12(3), 528-535.
[39]
Anhê, F.F.; Roy, D.; Pilon, G.; Dudonné, S.; Matamoros, S.; Varin, T.V.; Garofalo, C.; Moine, Q.; Desjardins, Y.; Levy, E.; Marette, A. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut, 2015, 64(6), 872-883.
[40]
Ohtomo, T.; Uehara, M.; Peñalvo, J.L.; Adlercreutz, H.; Katsumata, S.; Suzuki, K.; Takeda, K.; Masuyama, R.; Ishimi, Y. Comparative activities of daidzein metabolites, equol and O-desmethylangolensin, on bone mineral density and lipid metabolism in ovariectomized mice and in osteoclast cell cultures. Eur. J. Nutr., 2008, 47(5), 273-279.
[41]
Nakatsu, C.H.; Armstrong, A.; Clavijo, A.P.; Martin, B.R.; Barnes, S.; Weaver, C.M. Fecal bacterial community changes associated with isoflavone metabolites in postmenopausal women after soy bar consumption. PLoS One, 2014, 9(10), e108924
[42]
Hong, S.W.; Choi, J.Y.; Chung, K.S. Culture-based and denaturing gradient gel electrophoresis analysis of the bacterial community from Chungkookjang, a traditional Korean fermented soybean food. J. Food Sci., 2012, 77(10), M572-M578.
[43]
Frankenfeld, C.L.; Atkinson, C.; Wähälä, K.; Lampe, J.W. Obesity prevalence in relation to gut microbial environments capable of producing equol or O-desmethylangolensin from the isoflavone daidzein. Eur. J. Clin. Nutr., 2014, 68(4), 526-530.
[44]
Madak-Erdogan, Z.; Gong, P.; Zhao, Y.C.; Xu, L.; Wrobel, K.U.; Hartman, J.A.; Wang, M.; Cam, A.; Iwaniec, U.T.; Turner, R.T.; Twaddle, N.C.; Doerge, D.R.; Khan, I.A.; Katzenellenbogen, J.A.; Katzenellenbogen, B.S.; Helferich, W.G. Dietary licorice root supplementation reduces diet-induced weight gain, lipid deposition, and hepatic steatosis in ovariectomized mice without stimulating reproductive tissues and mammary gland. Mol. Nutr. Food Res., 2016, 60(2), 369-380.
[45]
Chen, K.L.; Madak-Erdogan, Z. Estrogen and Microbiota Crosstalk: Should We Pay Attention? Trends Endocrinol. Metab., 2016, 27(11), 752-755.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 7
Year: 2020
Published on: 18 May, 2020
Page: [578 - 583]
Pages: 6
DOI: 10.2174/1389557520666200103114123
Price: $65

Article Metrics

PDF: 27
HTML: 1