Huangqin-Huanglian Decoction Protects Liver against Non-alcoholic Fatty
Liver Disease in High Fat-diet Mice

Hongying      Yang; Dongyun      Wei; Yao      Zhang; Wenxuan      Jian

doi:10.2174/0118715303257018230927182802

Abstract

Background: Traditional Chinese medicine (TCM) has the advantage of low toxicity of natural ingredients, multiple targets and effects, and low medication costs. It has unique advantages for metabolic and chronic diseases. Huangqin-Huanglian decoction (HQHLD) is composed of Scutellariae Radix, Coptidis Rhizoma, Rehmanniae Radix, and Gentianae Radix Et Rhozima; it has great potential for the treatment of NAFLD with the modern pharmacological research and TCM theory, but there is still a relative lack of research on the potential targets and pharmacological effects of HQHLD.

Methods: In this work, we have used network pharmacology to predict the targets and signaling pathways of HQHLD, and validated NAFLD-related targets using the HFD model in order to explore more therapeutic drugs and methods for NAFLD. We collected the HQHLD ingredients and NAFLD targets through TCMSP, ETCM, DisGeNET, HGMD, MalaCards, OMIM, and TTD, built ingredients-target networks by Cytoscape, and screened key ingredients in HQHLD. DAVID and Metascape databases were used for GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking of the key ingredients and key targets was performed by AutoDock. We verified the effect of HQHLD on high-fat diet (HFD) mice by measuring the weight, liver weight index, and the level of TG, TC, LDL-C, and HDLC. HE staining and oil-red staining were performed to detect the damage and fat accumulation in the liver. The changes in INSR, PPAR-α, PPAR-γ, TNF-α, and caspase3 were experimented with WB.

Results: With the network pharmacology analysis, we found quercetin, baicalein, sitosterol, wogonin, oroxylin-A, glycyrrhizin, hydroberberine, berberine, sesamin, and carotene to be the main ingredients in HQHLD. According to KEGG pathway analysis, INSR, AKT, JNK1, PPAR-α, PPAR-γ, and the other 16 targets are the main targets of HQHLD in the treatment of NAFLD. We took HFD mice as the in vivo model of NAFLD. Our results showed that HQHLD could reduce liver weight, and TG and LDL-C levels, and increase HDL-C level in serum. By HE and oil red staining, we found that HQHLD could protect the morphology of hepatocytes and reduce fat in the liver. We also found HQHLD to protect the liver by increasing the expression of INSR and PPAR-α, and reducing the expression of PPAR-γ, TNF-α, and caspase3 in the liver.

Conclusion: In conclusion, our study has firstly studied the main ingredients and key targets of HQHDL in treating NAFLD by network pharmacology analysis, and preliminarily confirmed that HQHLD could alleviate NAFLD in a multi-target way by lowering fatty acids, and decreasing insulin resistance, inflammation, and apoptosis in the liver.

Keywords: Huangqin-Huanglian decoction, non-alcoholic fatty liver disease, high-fat diet, network pharmacology, inflammation, apoptosis.

« Previous Next »

Graphical Abstract

[1]
Rinella, M.E. Nonalcoholic fatty liver disease: A systematic review. JAMA,  2015, 313(22), 2263-2273.
 [http://dx.doi.org/10.1001/jama.2015.5370] [PMID: 26057287]

[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]
Fan, J.G.; Kim, S.U.; Wong, V.W.S. New trends on obesity and NAFLD in Asia. J. Hepatol.,  2017, 67(4), 862-873.
 [http://dx.doi.org/10.1016/j.jhep.2017.06.003] [PMID: 28642059]

[4]
Younossi, Z.M.; Koenig, A.B.; Abdelatif, D.; Fazel, Y.; Henry, L.; Wymer, M. Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes. Hepatology,  2016, 64(1), 73-84.
 [http://dx.doi.org/10.1002/hep.28431] [PMID: 26707365]

[5]
Fang, Y.L.; Chen, H.; Wang, C.L.; Liang, L. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model”. World J. Gastroenterol.,  2018, 24(27), 2974-2983.
 [http://dx.doi.org/10.3748/wjg.v24.i27.2974] [PMID: 30038464]

[6]
Buzzetti, E.; Pinzani, M.; Tsochatzis, E.A. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism,  2016, 65(8), 1038-1048.
 [http://dx.doi.org/10.1016/j.metabol.2015.12.012] [PMID: 26823198]

[7]
Gawrieh, S. Saroglitazar, a PPAR-α/γ agonist, for treatment of NAFLD: A randomized controlled double-blind phase 2 trial. Hepatology,  2021, 74(4), 1809-1824.
 [http://dx.doi.org/10.1002/hep.31843]

[8]
Byrne, C.D.; Targher, G. NAFLD: A multisystem disease. J. Hepatol.,  2015, 62(S1), S47-S64.
 [http://dx.doi.org/10.1016/j.jhep.2014.12.012] [PMID: 25920090]

[9]
Xing, L.J.; Zhang, L.; Liu, T.; Hua, Y.Q.; Zheng, P.Y.; Ji, G. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. Eur. J. Pharmacol.,  2011, 668(3), 467-471.
 [http://dx.doi.org/10.1016/j.ejphar.2011.07.036] [PMID: 21839075]

[10]
Gonzalez, A. Role of oxidative stress in hepatic and extrahepatic dysfunctions during nonalcoholic fatty liver disease (NAFLD). Oxid. Med. Cell. Longev.,  2020, 2020, 1617805.
 [http://dx.doi.org/10.1155/2020/1617805]

[11]
He, X.W.; Yu, D.; Li, W.L.; Zheng, Z.; Lv, C.L.; Li, C.; Liu, P.; Xu, C.Q.; Hu, X.F.; Jin, X.P. Anti-atherosclerotic potential of baicalin mediated by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1/ABCG1 pathway. Biomed. Pharmacother.,  2016, 83, 257-264.
 [http://dx.doi.org/10.1016/j.biopha.2016.06.046] [PMID: 27389392]

[12]
Jin, X. Baicalin mitigates cognitive impairment and protects neurons from microglia-mediated neuroinflammation via suppressing NLRP3 inflammasomes and TLR4/NF-κB signaling pathway. 2019, 25(5), 575-590.
 [http://dx.doi.org/10.1111/cns.13086]

[13]
Li, Y.; Liu, T.; Li, Y.; Han, D.; Hong, J.; Yang, N.; He, J.; Peng, R.; Mi, X.; Kuang, C.; Zhou, Y.; Han, Y.; Shi, C.; Li, Z.; Guo, X. Baicalin ameliorates cognitive impairment and protects microglia from lps-induced neuroinflammation via the SIRT1/HMGB1 pathway. Oxid. Med. Cell. Longev.,  2020, 2020, 1-16.
 [http://dx.doi.org/10.1155/2020/4751349] [PMID: 33029280]

[14]
Jin, M.; Feng, H.; Wang, Y.; Yan, S.; Shen, B.; Li, Z.; Qin, H.; Wang, Q.; Li, J.; Liu, G. Gentiopicroside ameliorates oxidative stress and lipid accumulation through nuclear factor erythroid 2-related factor 2 activation. Oxid. Med. Cell. Longev.,  2020, 2020, 1-13.
 [http://dx.doi.org/10.1155/2020/2940746] [PMID: 32655764]

[15]
Yang, H.X.; Shang, Y.; Jin, Q.; Wu, Y.L.; Liu, J.; Qiao, C.Y.; Zhan, Z.Y.; Ye, H.; Nan, J.X.; Lian, L.H. Gentiopicroside ameliorates the progression from hepatic steatosis to fibrosis induced by chronic alcohol intake. Biomol. Ther.,  2020, 28(4), 320-327.
 [http://dx.doi.org/10.4062/biomolther.2020.008] [PMID: 32248671]

[16]
Zhang, Y.; Yang, X.; Wang, S.; Song, S.; Yang, X. Gentiopicroside prevents alcoholic liver damage by improving mitochondrial dysfunction in the rat model. Phytother. Res.,  2021, 35(4), 2230-2251.
 [http://dx.doi.org/10.1002/ptr.6981] [PMID: 33300653]

[17]
Wang, X.; Wang, Z.Y.; Zheng, J.H.; Li, S. TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches. Chin. J. Nat. Med.,  2021, 19(1), 1-11.
 [http://dx.doi.org/10.1016/S1875-5364(21)60001-8] [PMID: 33516447]

[18]
Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform.,  2014, 6(1), 13.
 [http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]

[19]
Xu, H.Y.; Zhang, Y.Q.; Liu, Z.M.; Chen, T.; Lv, C.Y.; Tang, S.H.; Zhang, X.B.; Zhang, W.; Li, Z.Y.; Zhou, R.R.; Yang, H.J.; Wang, X.J.; Huang, L.Q. ETCM: An encyclopaedia of traditional Chinese medicine. Nucleic Acids Res.,  2019, 47(D1), D976-D982.
 [http://dx.doi.org/10.1093/nar/gky987] [PMID: 30365030]

[20]
Piñero, J.; Bravo, À.; Queralt-Rosinach, N.; Gutiérrez-Sacristán, A.; Deu-Pons, J.; Centeno, E.; García-García, J.; Sanz, F.; Furlong, L.I. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res.,  2017, 45(D1), D833-D839.
 [http://dx.doi.org/10.1093/nar/gkw943] [PMID: 27924018]

[21]
Rappaport, N.; Twik, M.; Plaschkes, I.; Nudel, R.; Iny Stein, T.; Levitt, J.; Gershoni, M.; Morrey, C.P.; Safran, M.; Lancet, D. MalaCards: An amalgamated human disease compendium with diverse clinical and genetic annotation and structured search. Nucleic Acids Res.,  2017, 45(D1), D877-D887.
 [http://dx.doi.org/10.1093/nar/gkw1012] [PMID: 27899610]

[22]
Amberger, J.S.; Bocchini, C.A.; Schiettecatte, F.; Scott, A.F.; Hamosh, A. OMIM.org: Online mendelian inheritance in man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res.,  2015, 43(D1), D789-D798.
 [http://dx.doi.org/10.1093/nar/gku1205] [PMID: 25428349]

[23]
Wang, Y.; Zhang, S.; Li, F.; Zhou, Y.; Zhang, Y.; Wang, Z.; Zhang, R.; Zhu, J.; Ren, Y.; Tan, Y.; Qin, C.; Li, Y.; Li, X.; Chen, Y.; Zhu, F. Therapeutic target database 2020: Enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res.,  2019, 48(D1), gkz981.
 [http://dx.doi.org/10.1093/nar/gkz981] [PMID: 31691823]

[24]
Mong, M.; Chao, C.; Yin, M. Histidine and carnosine alleviated hepatic steatosis in mice consumed high saturated fat diet. Eur. J. Pharmacol.,  2011, 653(1-3), 82-88.
 [http://dx.doi.org/10.1016/j.ejphar.2010.12.001] [PMID: 21167151]

[25]
Rabot, S.; Membrez, M.; Blancher, F.; Berger, B.; Moine, D.; Krause, L.; Bibiloni, R.; Bruneau, A.; Gérard, P.; Siddharth, J.; Lauber, C.L.; Chou, C.J. High fat diet drives obesity regardless the composition of gut microbiota in mice. Sci. Rep.,  2016, 6(1), 32484.
 [http://dx.doi.org/10.1038/srep32484] [PMID: 27577172]

[26]
Walewski, J.L.; Ge, F.; Lobdell, H.I.V.; Levin, N.; Schwartz, G.J.; Vasselli, J.R.; Pomp, A.; Dakin, G.; Berk, P.D. Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity. Obesity,  2014, 22(7), 1643-1652.
 [http://dx.doi.org/10.1002/oby.20725] [PMID: 24550067]

[27]
Younossi, Z.; Anstee, Q.M.; Marietti, M.; Hardy, T.; Henry, L.; Eslam, M.; George, J.; Bugianesi, E. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol.,  2018, 15(1), 11-20.
 [http://dx.doi.org/10.1038/nrgastro.2017.109] [PMID: 28930295]

[28]
Luo, Y.; Li, D.; Liao, Y.; Cai, C.; Wu, Q.; Ke, H.; Liu, X.; Li, H.; Hong, H.; Xu, Y.; Wang, Q.; Fang, J.; Fang, S. Systems pharmacology approach to investigate the mechanism of kai-xin-san in alzheimer’s disease. Front. Pharmacol.,  2020, 11, 381.
 [http://dx.doi.org/10.3389/fphar.2020.00381] [PMID: 32317964]

[29]
Bak, E.J.; Kim, J.; Choi, Y.H.; Kim, J.H.; Lee, D.E.; Woo, G.H.; Cha, J.H.; Yoo, Y.J. Wogonin ameliorates hyperglycemia and dyslipidemia via PPARα activation in db/db mice. Clin. Nutr.,  2014, 33(1), 156-163.
 [http://dx.doi.org/10.1016/j.clnu.2013.03.013] [PMID: 23623334]

[30]
Chen, J.; Liu, J.; Wang, Y.; Hu, X.; Zhou, F.; Hu, Y.; Yuan, Y.; Xu, Y. Wogonin mitigates nonalcoholic fatty liver disease via enhancing PPARα/AdipoR2, in vivo and in vitro. Biomed. Pharmacother.,  2017, 91, 621-631.
 [http://dx.doi.org/10.1016/j.biopha.2017.04.125] [PMID: 28486193]

[31]
Zhang, R.; Yu, Y.; Hu, S.; Zhang, J.; Yang, H.; Han, B.; Cheng, Y.; Luo, X. Sesamin ameliorates hepatic steatosis and inflammation in rats on a high-fat diet via LXRα and PPARα. Nutr. Res.,  2016, 36(9), 1022-1030.
 [http://dx.doi.org/10.1016/j.nutres.2016.06.015] [PMID: 27632923]

[32]
Baradaran Rahimi, V.; Askari, V.R.; Hosseinzadeh, H. Promising influences of Scutellaria baicalensis and its two active constituents, baicalin, and baicalein, against metabolic syndrome: A review. Phytother. Res.,  2021, 35(7), 3558-3574.
 [http://dx.doi.org/10.1002/ptr.7046] [PMID: 33590943]

[33]
Jin, H.; Lian, N.; Bian, M.; Zhang, C.; Chen, X.; Shao, J.; Wu, L.; Chen, A.; Guo, Q.; Zhang, F.; Zheng, S. Oroxylin A prevents alcohol-induced hepatic steatosis through inhibition of hypoxia inducible factor 1alpha. Chem. Biol. Interact.,  2018, 285, 14-20.
 [http://dx.doi.org/10.1016/j.cbi.2018.02.025] [PMID: 29476730]

[34]
Lu, L.; Guo, Q.; Zhao, L. Overview of oroxylin A: A promising flavonoid compound. Phytother. Res.,  2016, 30(11), 1765-1774.
 [http://dx.doi.org/10.1002/ptr.5694] [PMID: 27539056]

[35]
Feng, S.; Gan, L.; Yang, C.S. Effects of stigmasterol and β-sitosterol on nonalcoholic fatty liver disease in a mouse model: A lipidomic analysis. J. Agric. Food Chem.,  2018, 66(13), 3417-3425.
 [http://dx.doi.org/10.1021/acs.jafc.7b06146]

[36]
Chen, L.; Liu, J.; Mei, G.; Chen, H.; Peng, S.; Zhao, Y.; Yao, P.; Tang, Y. Quercetin and non-alcoholic fatty liver disease: A review based on experimental data and bioinformatic analysis. Food Chem. Toxicol.,  2021, 154, 112314.
 [http://dx.doi.org/10.1016/j.fct.2021.112314] [PMID: 34087406]

[37]
Patel, R.V.; Mistry, B.M.; Shinde, S.K.; Syed, R.; Singh, V.; Shin, H.S. Therapeutic potential of quercetin as a cardiovascular agent. Eur. J. Med. Chem.,  2018, 155, 889-904.
 [http://dx.doi.org/10.1016/j.ejmech.2018.06.053] [PMID: 29966915]

[38]
Lu, Y.; Shao, M.; Xiang, H.; Zheng, P.; Wu, T.; Ji, G. Integrative transcriptomics and metabolomics explore the mechanism of kaempferol on improving nonalcoholic steatohepatitis. Food Funct.,  2020, 11(11), 10058-10069.
 [http://dx.doi.org/10.1039/D0FO02123G] [PMID: 33135718]

[39]
Feng, M.; Liu, F.; Xing, J.; Zhong, Y.; Zhou, X. Anemarrhena saponins attenuate insulin resistance in rats with high-fat diet-induced obesity via the IRS-1/PI3K/AKT pathway. J. Ethnopharmacol.,  2021, 277, 114251.
 [http://dx.doi.org/10.1016/j.jep.2021.114251] [PMID: 34052350]

[40]
Liu, Q.; Li, X.; Li, C.; Zheng, Y.; Peng, G. 1-deoxynojirimycin alleviates insulin resistance via activation of insulin signaling PI3K/AKT pathway in skeletal muscle of db/db mice. Molecules,  2015, 20(12), 21700-21714.
 [http://dx.doi.org/10.3390/molecules201219794] [PMID: 26690098]

[41]
Yang, P.; Liang, Y.; Luo, Y.; Li, Z.; Wen, Y.; Shen, J.; Li, R.; Zheng, H.; Gu, H.F.; Xia, N. Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway. Diabetes Metab. Syndr. Obes.,  2019, 12, 1013-1021.
 [http://dx.doi.org/10.2147/DMSO.S206867] [PMID: 31308717]

[42]
Mengxi, W.; Mo, L.; Renjie, Z.; Jing, W.; Dongya, C.; Hong, L. Ameliorating effect of sesamin on insulin resistance of hepatic L02 cells induced by high glucose/high insulin. Pak. J. Pharm. Sci.,  2019, 32(6), 2733-2739.
 [PMID: 31969308]

[43]
Kong, W.J.; Zhang, H.; Song, D.Q.; Xue, R.; Zhao, W.; Wei, J.; Wang, Y.M.; Shan, N.; Zhou, Z.X.; Yang, P.; You, X.F.; Li, Z.R.; Si, S.Y.; Zhao, L.X.; Pan, H.N.; Jiang, J.D. Berberine reduces insulin resistance through protein kinase C–dependent up-regulation of insulin receptor expression. Metabolism,  2009, 58(1), 109-119.
 [http://dx.doi.org/10.1016/j.metabol.2008.08.013] [PMID: 19059538]

[44]
Liu, H.; Chen, G.; Zhang, W.; Zhu, J.Y.; Lin, Z.Q.; Gong, Z.C.; Wang, F.Q.; Jia, J.; Sun, Z.J.; Zhao, Y.F. Overexpression of macrophage migration inhibitory factor in adenoid cystic carcinoma: Correlation with enhanced metastatic potential. J. Cancer Res. Clin. Oncol.,  2013, 139(2), 287-295.
 [http://dx.doi.org/10.1007/s00432-012-1330-z] [PMID: 23064787]

[45]
Shi, G.; Zhong, S. Alcohol-associated cancer and deregulation of Pol III genes. Gene,  2017, 612, 25-28.
 [http://dx.doi.org/10.1016/j.gene.2016.09.046] [PMID: 27697617]

[46]
Han, L.; Shen, W.J.; Bittner, S.; Kraemer, F.B.; Azhar, S. PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part I: PPAR-α. Future Cardiol.,  2017, 13(3), 259-278.
 [http://dx.doi.org/10.2217/fca-2016-0059] [PMID: 28581332]

[47]
Lim, S.; Lee, K.S.; Lee, J.E.; Park, H.S.; Kim, K.M.; Moon, J.H.; Choi, S.H.; Park, K.S.; Kim, Y.B.; Jang, H.C. Effect of a new PPAR-gamma agonist, lobeglitazone, on neointimal formation after balloon injury in rats and the development of atherosclerosis. Atherosclerosis,  2015, 243(1), 107-119.
 [http://dx.doi.org/10.1016/j.atherosclerosis.2015.08.037] [PMID: 26363808]

[48]
Zhang, Z.Z.; Yu, X.H.; Tan, W.H. Baicalein inhibits macrophage lipid accumulation and inflammatory response by activating the PPARγ/LXRα pathway. Clin. Exp. Immunol.,  2022, 209(3), 316-325.
 [http://dx.doi.org/10.1093/cei/uxac062] [PMID: 35749304]

[49]
Hong, S.Y.; Ha, A.W. Effects of quercetin on cell differentiation and adipogenesis in 3T3-L1 adipocytes. Nutr. Res. Pract.,  2021, 15(4), 444-455.
 [http://dx.doi.org/10.4162/nrp.2021.15.4.444]

[50]
Li, D.J.; Sun, S.J.; Fu, J.T.; Ouyang, S.X.; Zhao, Q.J.; Su, L.; Ji, Q.X.; Sun, D.Y.; Zhu, J.H.; Zhang, G.Y.; Ma, J.W.; Lan, X.T.; Zhao, Y.; Tong, J.; Li, G.Q.; Shen, F.M.; Wang, P. NAD + -boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin. Theranostics,  2021, 11(9), 4381-4402.
 [http://dx.doi.org/10.7150/thno.53652] [PMID: 33754067]

[51]
Kim, D.H.; Jeong, D.; Kang, I.B.; Kim, H.; Song, K.Y.; Seo, K.H. Dual function of Lactobacillus kefiri DH5 in preventing high-fat-diet-induced obesity: Direct reduction of cholesterol and upregulation of PPAR-α in adipose tissue. Mol. Nutr. Food Res.,  2017, 61(11), 1700252.
 [http://dx.doi.org/10.1002/mnfr.201700252] [PMID: 28691342]

[52]
Marino, L.; Jornayvaz, F.R. Endocrine causes of nonalcoholic fatty liver disease. World J. Gastroenterol.,  2015, 21(39), 11053-11076.
 [http://dx.doi.org/10.3748/wjg.v21.i39.11053] [PMID: 26494962]

[53]
Li, L.; Fu, J.; Liu, D.; Sun, J.; Hou, Y.; Chen, C.; Shao, J.; Wang, L.; Wang, X.; Zhao, R.; Wang, H.; Andersen, M.E.; Zhang, Q.; Xu, Y.; Pi, J. Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARγ expression. Redox Biol.,  2020, 30, 101412.
 [http://dx.doi.org/10.1016/j.redox.2019.101412] [PMID: 31901728]

[54]
Feng, K.; Zhu, X.; Liu, G.; Kan, Q.; Chen, T.; Chen, Y.; Cao, Y. Dietary citrus peel essential oil ameliorates hypercholesterolemia and hepatic steatosis by modulating lipid and cholesterol homeostasis. Food Funct.,  2020, 11(8), 7217-7230.
 [http://dx.doi.org/10.1039/D0FO00810A] [PMID: 32760938]

[55]
Miller, M.; Stone, N.J.; Ballantyne, C.; Bittner, V.; Criqui, M.H.; Ginsberg, H.N.; Goldberg, A.C.; Howard, W.J.; Jacobson, M.S.; Kris-Etherton, P.M.; Lennie, T.A.; Levi, M.; Mazzone, T.; Pennathur, S. Triglycerides and cardiovascular disease: A scientific statement from the American Heart Association. Circulation,  2011, 123(20), 2292-2333.
 [http://dx.doi.org/10.1161/CIR.0b013e3182160726] [PMID: 21502576]

[56]
Montemayor, S.; Bouzas, C.; Mascaró, C.M.; Casares, M.; Llompart, I.; Abete, I.; Angullo-Martinez, E.; Zulet, M.Á.; Martínez, J.A.; Tur, J.A. Effect of dietary and lifestyle interventions on the amelioration of nafld in patients with metabolic syndrome: The FLIPAN study. Nutrients,  2022, 14(11), 2223.
 [http://dx.doi.org/10.3390/nu14112223] [PMID: 35684022]

[57]
Jacobson, T.A.; Maki, K.C.; Orringer, C.E.; Jones, P.H.; Kris-Etherton, P.; Sikand, G.; La Forge, R.; Daniels, S.R.; Wilson, D.P.; Morris, P.B.; Wild, R.A.; Grundy, S.M.; Daviglus, M.; Ferdinand, K.C.; Vijayaraghavan, K.; Deedwania, P.C.; Aberg, J.A.; Liao, K.P.; McKenney, J.M.; Ross, J.L.; Braun, L.T.; Ito, M.K.; Bays, H.E.; Brown, W.V.; Underberg, J.A. National lipid association recommendations for patient-centered management of dyslipidemia: Part 2. J. Clin. Lipidol.,  2015, 9(S6), S1-122.e1, S122.e1.
 [http://dx.doi.org/10.1016/j.jacl.2015.09.002] [PMID: 26699442]

[58]
Pérez-Mayorga, M.; Lopez-Lopez, J.P.; Chacon-Manosalva, M.A.; Castillo, M.G.; Otero, J.; Martinez-Bello, D.; Gomez-Arbelaez, D.; Cohen, D.D.; Lopez-Jaramillo, P. Insulin resistance markers to detect nonalcoholic fatty liver disease in a male hispanic population. Can. J. Gastroenterol. Hepatol.,  2022, 2022, 1-7.
 [http://dx.doi.org/10.1155/2022/1782221] [PMID: 35966932]

Rights & Permissions Print Cite

Article Metrics

29

2

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/0118715303257018230927182802	Print ISSN 1871-5303
Publisher Name Bentham Science Publisher	Online ISSN 2212-3873

Endocrine, Metabolic & Immune Disorders - Drug Targets

Huangqin-Huanglian Decoction Protects Liver against Non-alcoholic Fatty Liver Disease in High Fat-diet Mice

Abstract

Graphical Abstract

Related Journals

Related Books