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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Shugan Jiangzhi Decoction Alleviates Nonalcoholic Fatty Liver Disease (NAFLD) via Regulating AMPK/PPAR Signaling Pathway

Author(s): Lijuan Chen, Wen Li, Yanli Fu, Yuhe Lei, Wenjian Xie, Suihua Rong, Ning Li, Miaomiao Zhang, Jiayi He, Yanfen Chen* and Dinghong Wu*

Volume 21, Issue 13, 2024

Published on: 17 October, 2023

Page: [2740 - 2750] Pages: 11

DOI: 10.2174/1570180820666230828125057

Price: $65

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease. Shugan Jiangzhi Decoction (SJD), a traditional Chinese medicine (TCM) formula which consists of six Chinese herbs, has been used for treating hyperlipidemia, obesity, and fatty liver in Guangdong Provincial Hospital of Traditional Chinese Medicine for over twenty years.

Objective: This study aims to elucidate the chemical basis and the molecular mechanism of SJD against NAFLD.

Methods: The main components of SJD were determined by High Performance Liquid Chromatography (HPLC). Then the high-fat diet (HFD)-induced NAFLD rat model was established. After treatment with different doses of SJD, the body weight of rats was measured weekly. On the last day of the experiments, the hepatic morphology, histopathology changes, and the serum lipid levels were detected. Then techniques of network pharmacology were employed to predict the anti-NAFLD mechanism of SJD. At last, the expression levels of proteins were measured by western blot to verify the mechanism.

Results: Nine chemical constituents of SJD were identified from HPLC fingerprint spectrum. For the in vivo experiment, NAFLD rat model was constructed successfully by feeding high-fat diet (HFD) for 8 weeks. The following treatment with SJD for 6 weeks decreased the fatty droplet accumulation in the liver obviously. Meanwhile, the serum level of high-density lipoprotein cholesterol (HDL-c) was increased, while the levels of low-density lipoprotein cholesterol (LDL-c), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were decreased after SJD treatment (p < 0.05). The results of network pharmacology indicated that SJD might improve NAFLD via regulating the AMPK/PPAR signaling pathway. Then, the western blot assay confirmed that SJD activated the AMPK/PPAR signaling pathway in the liver of rats.

Conclusion: SJD improves HFD-induced NAFLD in rats via AMPK/PPAR signaling pathway. Thus, our study suggests that SJD can serve as a therapeutic agent for the prevention and treatment of NAFLD.

Keywords: Shugan jiangzhi decoction (SJD), network pharmacology, high performance liquid chromatography (HPLC), AMPK/PPAR signaling pathway, nonalcoholic fatty liver disease (NAFLD), Chinese medicine.

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[1]
Bellentani, S. The epidemiology of non-alcoholic fatty liver disease. Liver Int., 2017, 37(1), 81-84.
[http://dx.doi.org/10.1111/liv.13299] [PMID: 28052624]
[2]
Friedman, S.L.; Neuschwander-Tetri, B.A.; Rinella, M.; Sanyal, A.J. Mechanisms of NAFLD development and therapeutic strategies. Nat. Med., 2018, 24(7), 908-922.
[http://dx.doi.org/10.1038/s41591-018-0104-9] [PMID: 29967350]
[3]
Cohen, J.C.; Horton, J.D.; Hobbs, H.H. Human fatty liver disease: Old questions and new insights. Science, 2011, 332(6037), 1519-1523.
[http://dx.doi.org/10.1126/science.1204265] [PMID: 21700865]
[4]
Seitz, H.K.; Bataller, R.; Cortez-Pinto, H.; Gao, B.; Gual, A.; Lackner, C.; Mathurin, P.; Mueller, S.; Szabo, G.; Tsukamoto, H. Alcoholic liver disease. Nat. Rev. Dis. Primers, 2018, 4(1), 16.
[http://dx.doi.org/10.1038/s41572-018-0014-7] [PMID: 30115921]
[5]
Lewis, J.R.; Mohanty, S.R. Nonalcoholic fatty liver disease: A review and update. Dig. Dis. Sci., 2010, 55(3), 560-578.
[http://dx.doi.org/10.1007/s10620-009-1081-0] [PMID: 20101463]
[6]
Schmidt, N.H.; Svendsen, P.; Albarrán-Juárez, J.; Moestrup, S.K.; Bentzon, J.F. High-fructose feeding does not induce steatosis or non-alcoholic fatty liver disease in pigs. Sci. Rep., 2021, 11(1), 2807.
[http://dx.doi.org/10.1038/s41598-021-82208-1] [PMID: 33531575]
[7]
Tilg, H.; Moschen, A.R. Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology, 2010, 52(5), 1836-1846.
[http://dx.doi.org/10.1002/hep.24001] [PMID: 21038418]
[8]
Zheng, J.; Li, Z.; Manabe, Y.; Kim, M.; Goto, T.; Kawada, T.; Sugawara, T. Siphonaxanthin, a carotenoid from green algae, inhibits lipogenesis in hepatocytes via the suppression of liver x receptor α activity. Lipids, 2018, 53(1), 41-52.
[http://dx.doi.org/10.1002/lipd.12002] [PMID: 29446839]
[9]
Hashmi, S.; Wang, Y.; Parhar, R.S.; Collison, K.S.; Conca, W.; Al-Mohanna, F.; Gaugler, R. A C. elegans model to study human metabolic regulation. Nutr. Metab., 2013, 10(1), 31.
[http://dx.doi.org/10.1186/1743-7075-10-31] [PMID: 23557393]
[10]
Torres, D.M.; Williams, C.D.; Harrison, S.A. Features, diagnosis, and treatment of nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol., 2012, 10(8), 837-858.
[http://dx.doi.org/10.1016/j.cgh.2012.03.011] [PMID: 22446927]
[11]
Feng, Q.; Gou, X.; Meng, S.; Huang, C.; Zhang, Y.; Tang, Y.; Wang, W.; Xu, L.; Peng, J.; Hu, Y. Qushi huayu decoction inhibits hepatic lipid accumulation by activating amp-activated protein kinase in vivo and in vitro. Evid. Based Complement. Alternat. Med., 2013, 2013, 1-14.
[http://dx.doi.org/10.1155/2013/184358] [PMID: 23573117]
[12]
Hardie, D.G. AMP-activated protein kinase: Maintaining energy homeostasis at the cellular and whole-body levels. Annu. Rev. Nutr., 2014, 34(1), 31-55.
[http://dx.doi.org/10.1146/annurev-nutr-071812-161148] [PMID: 24850385]
[13]
Cho, K.; Kim, S.J.; Park, S.H.; Kim, S.; Park, T. Protective effect of Codonopsis lanceolata root extract against alcoholic fatty liver in the rat. J. Med. Food, 2009, 12(6), 1293-1301.
[http://dx.doi.org/10.1089/jmf.2009.0085] [PMID: 20041784]
[14]
Hong, M.; Li, S.; Wang, N.; Tan, H.Y.; Cheung, F.; Feng, Y. A biomedical investigation of the hepatoprotective effect of radix salviae miltiorrhizae and network pharmacology-based prediction of the active compounds and molecular targets. Int. J. Mol. Sci., 2017, 18(3), 620.
[http://dx.doi.org/10.3390/ijms18030620] [PMID: 28335383]
[15]
Zhang, W.; Li, J.; Wei, X.; Wang, Q.; Yang, J.; Hou, H.; Du, Z.; Wu, X. Effects of dibutyl phthalate on lipid metabolism in liver and hepatocytes based on PPARα/SREBP-1c/FAS/GPAT/AMPK signal pathway. Food Chem. Toxicol., 2021, 149, 112029.
[http://dx.doi.org/10.1016/j.fct.2021.112029] [PMID: 33508418]
[16]
Feng, Y.; Wu, Z.; Zhou, X.; Zhou, Z.; Fan, W. Knowledge discovery in traditional chinese medicine: State of the art and perspectives. Artif. Intell. Med., 2006, 38(3), 219-236.
[http://dx.doi.org/10.1016/j.artmed.2006.07.005] [PMID: 16930966]
[17]
Zuo, J.; Wang, X.; Liu, Y.; Ye, J.; Liu, Q.; Li, Y.; Li, S. Integrating network pharmacology and metabolomics study on anti-rheumatic mechanisms and antagonistic effects against methotrexate-induced toxicity of qing-luo-yin. Front. Pharmacol., 2018, 9, 1472.
[http://dx.doi.org/10.3389/fphar.2018.01472] [PMID: 30618762]
[18]
Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[http://dx.doi.org/10.1038/nchembio.118] [PMID: 18936753]
[19]
Fang, J.; Wang, L.; Wu, T.; Yang, C.; Gao, L.; Cai, H.; Liu, J.; Fang, S.; Chen, Y.; Tan, W.; Wang, Q. Network pharmacology-based study on the mechanism of action for herbal medicines in Alzheimer treatment. J. Ethnopharmacol., 2017, 196, 281-292.
[http://dx.doi.org/10.1016/j.jep.2016.11.034] [PMID: 27888133]
[20]
Bi, S.J.; Huang, Y.X.; Feng, L.M.; Yue, S.J.; Chen, Y.Y.; Fu, R.J.; Xu, D.Q.; Tang, Y.P. Network pharmacology-based study on immunomodulatory mechanism of danggui-yimucao herb pair for the treatment of RU486-induced abortion. J. Ethnopharmacol., 2022, 282, 114609.
[http://dx.doi.org/10.1016/j.jep.2021.114609] [PMID: 34508802]
[21]
Tu, S.P.; Quante, M.; Bhagat, G.; Takaishi, S.; Cui, G.; Yang, X.D.; Muthuplani, S.; Shibata, W.; Fox, J.G.; Pritchard, D.M.; Wang, T.C. IFN-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis. Cancer Res., 2011, 71(12), 4247-4259.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4009] [PMID: 21512143]
[22]
Ghiringhelli, F.; Apetoh, L.; Tesniere, A.; Aymeric, L.; Ma, Y.; Ortiz, C.; Vermaelen, K.; Panaretakis, T.; Mignot, G.; Ullrich, E.; Perfettini, J.L.; Schlemmer, F.; Tasdemir, E.; Uhl, M.; Génin, P.; Civas, A.; Ryffel, B.; Kanellopoulos, J.; Tschopp, J.; André, F.; Lidereau, R.; McLaughlin, N.M.; Haynes, N.M.; Smyth, M.J.; Kroemer, G.; Zitvogel, L. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors. Nat. Med., 2009, 15(10), 1170-1178.
[http://dx.doi.org/10.1038/nm.2028] [PMID: 19767732]
[23]
Diniz, T.A.; de Lima, Junior, E.A.; Teixeira, A.A.; Biondo, L.A.; da Rocha, L.A.F.; Valadão, I.C.; Silveira, L.S.; Cabral-Santos, C.; de Souza, C.O.; Rosa Neto, J.C. Aerobic training improves NAFLD markers and insulin resistance through AMPK-PPAR-α signaling in obese mice. Life Sci., 2021, 266, 118868.
[http://dx.doi.org/10.1016/j.lfs.2020.118868] [PMID: 33310034]
[24]
Bugianesi, E.; Leone, N.; Vanni, E.; Marchesini, G.; Brunello, F.; Carucci, P.; Musso, A.; De Paolis, P.; Capussotti, L.; Salizzoni, M.; Rizzetto, M. Expanding the natural history of nonalcoholic steatohepatitis: From cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology, 2002, 123(1), 134-140.
[http://dx.doi.org/10.1053/gast.2002.34168] [PMID: 12105842]
[25]
Marchesini, G.; Brizi, M.; Bianchi, G.; Tomassetti, S.; Bugianesi, E.; Lenzi, M.; McCullough, A.J.; Natale, S.; Forlani, G.; Melchionda, N. Nonalcoholic fatty liver disease: A feature of the metabolic syndrome. Diabetes, 2001, 50(8), 1844-1850.
[http://dx.doi.org/10.2337/diabetes.50.8.1844] [PMID: 11473047]
[26]
Grundy, S.M.; Brewer, H.B., Jr; Cleeman, J.I.; Smith, S.C., Jr; Lenfant, C. Definition of metabolic syndrome: Report of the national heart, lung, and blood institute/american heart association conference on scientific issues related to definition. Circulation, 2004, 109(3), 433-438.
[http://dx.doi.org/10.1161/01.CIR.0000111245.75752.C6] [PMID: 14744958]
[27]
Reisin, E.; Alpert, M.A. Definition of the metabolic syndrome: Current proposals and controversies. Am. J. Med. Sci., 2005, 330(6), 269-272.
[http://dx.doi.org/10.1097/00000441-200512000-00003] [PMID: 16355010]
[28]
Zhang, M.; Yuan, Y.; Wang, Q.; Li, X.; Men, J.; Lin, M. The chinese medicine chai hu li zhong tang protects against non-alcoholic fatty liver disease by activating AMPKα. Biosci. Rep., 2018, 38(6), BSR20180644.
[http://dx.doi.org/10.1042/BSR20180644] [PMID: 30291215]
[29]
Liang, Z.; Chen, X.; Shi, J.; Hu, H.; Xue, Y.; Ung, C.O.L. Efficacy and safety of traditional Chinese medicines for non-alcoholic fatty liver disease: A systematic literature review of randomized controlled trials. Chin. Med., 2021, 16(1), 9.
[http://dx.doi.org/10.1186/s13020-020-00422-x] [PMID: 33430929]
[30]
Vazirian, M.; Nabavi, S.M.; Jafari, S.; Manayi, A. Natural activators of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and their pharmacological activities. Food Chem. Toxicol., 2018, 122, 69-79.
[http://dx.doi.org/10.1016/j.fct.2018.09.079] [PMID: 30290216]
[31]
Dusabimana, T.; Park, E.J.; Je, J.; Jeong, K.; Yun, S.P.; Kim, H.J.; Kim, H.; Park, S.W. P2Y2R deficiency ameliorates hepatic steatosis by reducing lipogenesis and enhancing fatty acid β-oxidation through ampk and pgc-1α induction in high-fat diet-fed mice. Int. J. Mol. Sci., 2021, 22(11), 5528.
[http://dx.doi.org/10.3390/ijms22115528] [PMID: 34073834]

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