Polysaccharide from Angelica sinensis with medicinal and edible purposes ameliorated NAFLD by the bile acids mediated activation of FXR
DOI:
https://doi.org/10.5327/fst.04923Palavras-chave:
Angelica sinensis polysaccharide, Non-alcoholic fatty liver disease, Farnesoid X receptorResumo
Liver and gut communicates with each other through metabolites and the gut-liver axis plays a crucial role in lipid metabolism. Enterohepatic bile acid circulation is an important constitution of gut-liver axis. Farnesoid X receptor (FXR),a bile acid mediated nuclear receptor, is promising therapeutic targets for the non-alcoholic fatty liver disease (NAFLD). More and more studies have confirmed the effects of Angelica sinensis polysaccharide (ASP) on liver protection and lipid regulation. However, little attention has been paid to the role of ASP on the gut-liver axis, which is crucial to clarify how ASP play a role in liver protection after oral administration. In vivo and in vitro models of NAFLD were established to examine the effect of ASP on hepatic fat accumulation. Our results showed that ASP could alleviate liver fat accumulation. However, the expression of FXR was not changed when ASP directly acting on hepatocytes, while ASP could change the expression of FXR in liver and intestine of mice after oral administration. In addition, our results showed that ASP could promote the excretion of bile acids, thereby increasing cholesterol metabolism. Our research provided a new concept for the mechanism of ASP regulating liver lipid metabolism and exerting liver protection.
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Albillos, A., de Gottardi, A., & Rescigno, M. (2020). The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol, 72(3), 558-577.
Beigneux, A., Hofmann, A. F., & Young, S. G. (2002). Human CYP7A1 deficiency: progress and enigmas. J Clin Invest, 110(1), 29-31.
Chambers, K. F., Day, P. E., Aboufarrag, H. T., & Kroon, P. A. (2019). Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review. Nutrients, 11(11), 2588.
Chiang, J. Y. L., & Ferrell, J. M. (2020). Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy. Am J Physiol Gastrointest Liver Physiol, 318(3), G554-G573.
Chiang, J. Y. L., & Ferrell, J. M. (2022). Discovery of farnesoid X receptor and its role in bile acid metabolism. Mol Cell Endocrinol, 548, 111618.
Chu, X., Zhou, Y., Zhang, S., Liu, S., Li, G., & Xin, Y. (2022). Chaetomorpha linum polysaccharides alleviate NAFLD in mice by enhancing the PPARalpha/CPT-1/MCAD signaling. Lipids Health Dis, 21(1), 140.
Garcia-Diez, F., Garcia-Mediavilla, V., Bayon, J. E., & Gonzalez-Gallego, J. (1996). Pectin feeding influences fecal bile acid excretion, hepatic bile acid and cholesterol synthesis and serum cholesterol in rats. J Nutr, 126(7), 1766-1771.
He, Z., Guo, T., Cui, Z., Xu, J., Wu, Z., Yang, X., Hu, H., Mei, H., Zhou, J., Zhang, Y., & Wang, K. (2022). New understanding of Angelica sinensis polysaccharide improving fatty liver: The dual inhibition of lipid synthesis and CD36-mediated lipid uptake and the regulation of alcohol metabolism. Int J Biol Macromol, 207, 813-825.
Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R. G., Krausz, K. W., Cai, J., Qi, Y., Fang, Z. Z., Takahashi, S., Tanaka, N., Desai, D., Amin, S. G., Albert, I., Patterson, A. D., & Gonzalez, F. J. (2015). Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest, 125(1), 386-402.
Jiang, L., Zhang, H., Xiao, D., Wei, H., & Chen, Y. (2021). Farnesoid X receptor (FXR): Structures and ligands. Comput Struct Biotechnol J, 19, 2148-2159.
Li, J., & Dawson, P. A. (2019). Animal models to study bile acid metabolism. Biochim Biophys Acta Mol Basis Dis, 1865(5), 895-911.
Li, X., Cui, W., Cui, Y., Song, X., Jia, L., & Zhang, J. (2022). Stropharia rugoso-annulata acetylated polysaccharides alleviate NAFLD via Nrf2/JNK1/AMPK signaling pathways. Int J Biol Macromol, 215, 560-570.
Marasca, E., Boulos, S., & Nystrom, L. (2020). Bile acid-retention by native and modified oat and barley beta-glucan. Carbohydr Polym, 236, 116034.
Powell, E. E., Wong, V. W., & Rinella, M. (2021). Non-alcoholic fatty liver disease. Lancet, 397(10290), 2212-2224.
Schumacher, J. D., & Guo, G. L. (2019). Pharmacologic Modulation of Bile Acid-FXR-FGF15/FGF19 Pathway for the Treatment of Nonalcoholic Steatohepatitis. Handb Exp Pharmacol, 256, 325-357.
Shin, D. J., & Wang, L. (2019). Bile Acid-Activated Receptors: A Review on FXR and Other Nuclear Receptors. Handb Exp Pharmacol, 256, 51-72.
Wang, K., Cao, P., Wang, H., Tang, Z., Wang, N., Wang, J., & Zhang, Y. (2016). Chronic administration of Angelica sinensis polysaccharide effectively improves fatty liver and glucose homeostasis in high-fat diet-fed mice. Sci Rep, 6, 26229.
Wang, K., Cheng, F., Pan, X., Zhou, T., Liu, X., Zheng, Z., Luo, L., & Zhang, Y. (2017). Investigation of the transport and absorption of Angelica sinensis polysaccharide through gastrointestinal tract both in vitro and in vivo. Drug Deliv, 24(1), 1360-1371.
Watanabe, M., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., Moore, D. D., & Auwerx, J. (2004). Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest, 113(10), 1408-1418.
Xu, Y., Guo, W., Zhang, C., Chen, F., Tan, H. Y., Li, S., Wang, N., & Feng, Y. (2020). Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application. Front Pharmacol, 11, 601.
Yang, C., Huang, S., Lin, Z., Chen, H., Xu, C., Lin, Y., Sun, H., Huang, F., Lin, D., & Guo, F. (2022). Polysaccharides from Enteromorpha prolifera alleviate hypercholesterolemia via modulating the gut microbiota and bile acid metabolism. Food Funct, 13(23), 12194-12207.
Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016). Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64(1), 73-84.
Zhai, Y., Zhou, W., Yan, X., Qiao, Y., Guan, L., Zhang, Z., Liu, H., Jiang, J., Liu, J., & Peng, L. (2022). Astragaloside IV ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling. Phytomedicine, 107, 154444.
Zhang, Y., Zhou, T., Wang, H., Cui, Z., Cheng, F., & Wang, K. P. (2016). Structural characterization and in vitro antitumor activity of an acidic polysaccharide from Angelica sinensis (Oliv.) Diels. Carbohydr Polym, 147, 401-408.