Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics

Yuping Zhou; Ze Dai; Kaili Deng; Yubin Wang; Jiamin Ying; Donghui Chu; Jinyue Zhou; Chunlan Tang

doi:10.1016/j.jpha.2023.05.012

Volume 13 Issue 9

Sep. 2023

Turn off MathJax

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(9): 1058-1069

Yuping Zhou, Ze Dai, Kaili Deng, Yubin Wang, Jiamin Ying, Donghui Chu, Jinyue Zhou, Chunlan Tang. Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics[J]. Journal of Pharmaceutical Analysis, 2023, 13(9): 1058-1069. doi: 10.1016/j.jpha.2023.05.012

Citation:

Yuping Zhou, Ze Dai, Kaili Deng, Yubin Wang, Jiamin Ying, Donghui Chu, Jinyue Zhou, Chunlan Tang. Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics[J]. Journal of Pharmaceutical Analysis, 2023, 13(9): 1058-1069. doi: 10.1016/j.jpha.2023.05.012

Citation:

Yuping Zhou, Ze Dai, Kaili Deng, Yubin Wang, Jiamin Ying, Donghui Chu, Jinyue Zhou, Chunlan Tang. Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics[J]. Journal of Pharmaceutical Analysis, 2023, 13(9): 1058-1069. doi: 10.1016/j.jpha.2023.05.012

PDF( 5043 KB)

Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics

doi: 10.1016/j.jpha.2023.05.012

a. The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China;
b. School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China;
c. Institute of Digestive Disease of Ningbo University, Ningbo, Zhejiang, 315020, China

Funds:

This work was supported by Ningbo Natural Science Foundation (Grant No.: 2022J229), Project of Ningbo Leading Medical & Health Discipline (Project No.: 2022–S04), Opened-end Fund of Key Laboratory (Grant No.: KFJJ-202101), and Graduate Student Scientific Research and Innovation Fund of Ningbo University (Grant No.: IF2022193).

Received Date: Feb. 08, 2023
Accepted Date: May 21, 2023
Rev Recd Date: Apr. 19, 2023
Publish Date: May 24, 2023

Abstract

Abstract

Nonalcoholic fatty liver disease (NAFLD) has developed into the most common chronic liver disease and can lead to liver cancer. Our laboratory previously developed a novel prescription for NAFLD, “Eight Zhes Decoction” (EZD), which has shown good curative effects in clinical practice. However, the pharmacodynamic material basis and mechanism have not yet been revealed. A strategy integrating lipidomics, network pharmacology and pharmacokinetics was used to reveal the active components and mechanisms of EZD against NAFLD. The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice. Furthermore, glycerophospholipid metabolism, arachidonic acid metabolism, glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA (PLA2G4A) and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid, 12(S)-hydroxyeicosatetraenoic acid, leukotriene B4, prostaglandin E2, phosphatidylcholines (PCs) and triacylglycerols (TGs) as the main lipids were found to be involved in the treatment of NAFLD by EZD. Importantly, naringenin, artemetin, canadine, and bicuculline were identified as the active ingredients of EZD against NAFLD; in particular, naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver. This research provides valuable data and theoretical support for the application of EZD against NAFLD.
- Eight Zhes Decoction,
- Nonalcoholic fatty liver disease,
- Lipidomics,
- Network pharmacology,
- Pharmacokinetics

FullText(HTML)

References(44)

References

E. Bugianesi, S. Petta, NAFLD/NASH, J. Hepatol. 77 (2022) 549-550.

M.H. Le, Y.H. Yeo, X. Li, et al., 2019 lobal NAFLD prevalence: systematic review and meta-analysis, Clin. Gastroenterol. Hepatol. 20 (2022) 2809-2817.e28.

S.L. Friedman, B.A. Neuschwander-Tetri, M. Rinella, et al., Mechanisms of NAFLD development and therapeutic strategies, 24 (2018) 908-922.

C. Alonso, D. Fernandez-Ramos, M. Varela-Rey, et al., Metabolomic identification of subtypes of nonalcoholic steatohepatitis, Gastroenterology 152 (2017) 1449-1461.e7.

R.J. Perry, V.T. Samuel, K.F. Petersen, et al., The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes, Nature 510 (2014) 84-91.

P.K. Luukkonen, Y. Zhou, S. Sadevirta, et al., Hepatic ceramides dissociate steatosis and insulin resistance in patients with non-alcoholic fatty liver disease, J. Hepatol. 64 (2016) 1167-1175.

M.S. Han, S.Y. Park, K. Shinzawa, et al., Lysophosphatidylcholine as a death effector in the of hepatocytes, J. Lipid Res. 49 (2008) 84-97.

A. Krishnan, T.S. Abdullah, T. Mounajjed, et al., A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition, Am. J. Physiol. Gastrointest. Liver Physiol. 312 (2017) G666-G680.

E. Vilar-Gomez, Y. Martinez-Perez, L. Calzadilla-Bertot, et al., Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis, Gastroenterology 149 (2015) 367-378.e5.

R. Xu, J. Pan, W. Zhou, et al., Recent advances in lean NAFLD, Biomed. Pharmacother. 153(2022), 113331.

F. Chen, S. Esmaili, G.B Rogers, et al., Lean NAFLD: distinct entity shaped by differential metabolic adaptation, Hepatology 71 (2020) 1213-1227.

M. Shao, Y. Lu, H. Xiang, et al., Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine, Front. Pharmacol. 13 (2022), 971561.

Y. Deng, M. Pan, H. Nie, et al., Lipidomic analysis of the protective effects of San on non-alcoholic fatty liver disease in rats, Molecules 24 (2019), 3943.

S.-H. Park, J.-E. Lee, S.M. Lee, et al., An unbiased lipidomics approach identifies key lipid molecules as potential therapeutic targets of -tang against non-alcoholic fatty liver diseases in a mouse model of obesity, J. Ethnopharmacol. 260 (2020), 112999.

Y. Zhou, J. Yang, P. Yang, et al., Prospective cohort study of “Eight zhes“ Decoction in the treatment of non-alcoholic steatohepatitis. 36 (2019) 2197-2201.

J. Ru, P. Li, J. Wang, et al., TCMSP: database of systems pharmacology for drug discovery from herbal medicines, 6 (2014), 13.

D. Szklarczyk, A. Santos, C. von Mering, et al., S 5: ugmenting protein-chemical interaction networks with tissue and affinity data, Nucleic Acids Res. 44(2016) D380-D384.

D. Gfeller, O. Michielin, V. Zoete, Shaping the interaction landscape of bioactive molecules, Bioinformatics 29 (2013) 3073-3079.

X. Wang, Y. Shen, S. Wang, et al., 2017 update: web server for potential drug target identification with a comprehensive target pharmacophore database, Nucleic Acids Res. 45 (2017) W356-W360.

M.J Keiser, B.L Roth, B.N. Armbruster, et al., Relating protein pharmacology by ligand chemistry, Nat. Biotechnol. 25 (2007) 197-206.

G. Stelzer, N. Rosen, I. Plaschkes, et al., The genecards suite: rom gene data mining to disease genome sequence analyses, 54 (2016) 1.30.1-1.30.33.

D.W. Huang, B.T Sherman, R.A. Lempicki, Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources, Nat. Protoc. 4 (2009) 44-57.

P. Shannon, A. Markiel, O. Ozier, et al., Cytoscape: software environment for integrated models of biomolecular interaction networks, . 13 (2003) 2498-2504.

H.M. Berman, J. Westbrook, Z. Feng, et al., The protein data bank, Nucleic Acids Res. 28 (2000) 235-242.

S. Kim, J. Chen, T. Cheng, et al., PubChem 2023 update, Nucleic Acids Res. 51 (2023) D1373-D1380.

D.S. Goodsell, A.J. Olson, Automated docking of substrates to proteins by simulated annealing, Proteins 8 (1990) 195-202.

C.A. Schneider, W.S. Rasband, K.W. Eliceiri, NIH Image to ImageJ: 25 years of image analysis, Nat. Methods 9(2012) 671-675.

Y. Zhang, J. Lv, J. Zhang, et al., Lipidomic-based investigation into the therapeutic effects of polyene phosphatidylcholine and Dan on rats with non-alcoholic fatty liver disease, Biomed. Chromatogr. 36 (2022), e5271.

X. Li, J. Ge, Y. Li, et al., Integrative lipidomic and transcriptomic study unravels the therapeutic effects of A and D on non-alcoholic fatty liver disease, Acta Pharm. Sin. B 11 (2021) 3527-3541.

H. Liu, T. Chen, X. Xie, et al., Hepatic lipidomics analysis reveals the ameliorative effects of highland barley β-glucan on western diet-induced nonalcoholic fatty liver disease mice, J. Agric. Food Chem. 69 (2021) 9287-9298.

A. Kotronen, V.R. Velagapudi, L. Yetukuri, et al., Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations, Diabetologia 52 (2009) 684-690.

D.L. Gorden, D.S. Myers, P.T. Ivanova, et al., Biomarkers of NAFLD progression: lipidomics approach to an epidemic, J. Lipid Res. 56 (2015) 722-736.

R. Mayo, J. Crespo, I. Martinez-Arranz, et al., Metabolomic-based noninvasive serum test to diagnose nonalcoholic steatohepatitis: esults from discovery and validation cohorts, 2 (2018) 807-820.

F. Bril, L. Millan, S. Kalavalapalli, et al., Use of a metabolomic approach to non-invasively diagnose non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus, 20 (2018) 1702-1709.

J. Simon, M. Nunez-Garcia, P. Fernandez-Tussy, et al., Targeting hepatic glutaminase 1 ameliorates non-alcoholic steatohepatitis by restoring very-low-density lipoprotein triglyceride assembly, . 31 (2020) 605-622.e10.

P. Puri, R.A. Baillie, M.M. Wiest, et al., A lipidomic analysis of nonalcoholic fatty liver disease, Hepatology 46 (2007) 1081-1090.

J. Barr, J. Caballeria, I. Martinez-Arranz, et al., Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression, J. Proteome Res. 11 (2012) 2521-2532.

Z. Gai, M. Visentin, T. Gui, et al., Effects of farnesoid X receptor activation on arachidonic acid metabolism, NF-κB signaling, and hepatic inflammation, Mol. Pharmacol. 94 (2018) 802-811.

X. Liu, K. Wang, L. Wang, et al., Hepatocyte leukotriene B4 receptor 1 promotes NAFLD development in obesity, Hepatology 2022. https://doi.org/10.1002/hep.32708.

W. Wang, X. Zhong, J. Guo, Role of 2-series prostaglandins in the pathogenesis of type 2 diabetes mellitus and non-alcoholic fatty liver disease (Review), Int. J. Mol. Med. 47 (2021), 114.

J. Henkel, K. Frede, N. Schanze, et al., Stimulation of fat accumulation in hepatocytes by PGE₂-dependent repression of hepatic lipolysis, β-oxidation and VLDL-synthesis, Lab. Invest. 92 (2012) 1597-1606.

M.-Y. Chung, E. Mah, C. Masterjohn, et al., Green tea lowers hepatic COX-2 and prostaglandin E2 in rats with dietary fat-induced nonalcoholic steatohepatitis, J. Med. Food 18 (2015) 648-655.

Z. Namkhah, F. Naeini, S. Mahdi Rezayat, et al., Does naringenin supplementation improve lipid profile, severity of hepatic steatosis and probability of liver fibrosis in overweight/obese patients with NAFLD? A randomised, double-blind, placebo-controlled, clinical trial, Int. J. Clin. Pract. 75 (2021), e14852.

F. Naeini, Z. Namkhah, H. Tutunchi, et al., Effects of naringenin supplementation in overweight/obese patients with non-alcoholic fatty liver disease: Study protocol for a randomized double-blind clinical trial, Trials 22 (2021), 801.

Relative Articles

Supplements(0)

Cited By

Proportional views