Exploring the Potential Mechanisms of Action of Gentiana Veitchiorum Hemsl. Extract in the Treatment of Cholestasis using UPLC-MS/MS, Systematic Network Pharmacology, and Molecular Docking


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Abstract

Introduction:Gentiana veitchiorum Hemsl. (GV) has a long history in Tibetan medicine for treating hepatobiliary disease cholestasis. However, the mechanisms mediating its efficacy in treating cholestasis have yet to be determined.

Aim:To elucidate the mechanisms of action of GV in the treatment of cholestasis, an integrated approach combining ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis with network pharmacology was established.

Materials and Methods:A comprehensive analysis of the chemical composition of GV was achieved by UPLC-MS/MS. Subsequently, a network pharmacology method that integrated target prediction, a protein-protein interaction (PPI) network, gene set enrichment analysis, and a component- target-pathway network was established, and finally, molecular docking and experiments in vitro were conducted to verify the predicted results.

Results:Twenty compounds that were extracted from GV were identified by UPLC-MS/MS analysis. Core proteins such as AKT1, TNF, and IL6 were obtained through screening in the Network pharmacology PPI network. The Kyoto Encyclopedia of the Genome (KEGG) pathway predicted that GV could treat cholestasis by acting on signaling pathways such as TNF/IL-17 / PI3K-Akt. Network pharmacology suggested that GV might exert a therapeutic effect on cholestasis by regulating the expression levels of inflammatory mediators, and the results were further confirmed by the subsequent construction of an LPS-induced RAW 264.7 cell model.

Conclusions:In this study, UPLC-MS/MS analysis, network pharmacology, and experiment validation were used to explore potential mechanisms of action of GV in the treatment of cholestasis.

About the authors

Yue Wang

, Medical College of Qinghai University

Email: info@benthamscience.net

Nixia Tan

, Medical College of Qinghai University

Email: info@benthamscience.net

Rong Su

, Medical College of Qinghai University

Email: info@benthamscience.net

Zhenhua Liu

, Medical College of Qinghai University

Email: info@benthamscience.net

Na Hu

Qinghai Provincial Key Laboratory of Tibetan Medicine Research and CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology

Email: info@benthamscience.net

Qi Dong

Qinghai Provincial Key Laboratory of Tibetan Medicine Research and CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology

Author for correspondence.
Email: info@benthamscience.net

References

  1. Wu, Q.Y.; Wong, Z.C.F.; Wang, C.; Fung, A.H.Y.; Wong, E.O.Y.; Chan, G.K.L.; Dong, T.T.X.; Chen, Y.; Tsim, K.W.K. Isoorientin derived from Gentiana veitchiorum Hemsl. flowers inhibits melanogenesis by down-regulating MITF-induced tyrosinase expression. Phytomedicine, 2019, 57, 129-136. doi: 10.1016/j.phymed.2018.12.006 PMID: 30668315
  2. Li, S.; Wan, C.; He, L.; Yan, Z.; Wang, K.; Yuan, M.; Zhang, Z. Rapid identification and quantitative analysis of chemical constituents of Gentiana veitchiorum by UHPLC-PDA-QTOF-MS. Rev. Bras. Farmacogn., 2017, 27(2), 188-194. doi: 10.1016/j.bjp.2016.10.003
  3. Li, S.; Wan, C.; Yuan, M.; Liu, X.; Zhao, Y.; Zhang, Z. Study on flavonoid glycosides from Gentiana veitchiorum. Chin. Tradit. Herbal Drugs, 2016, 47(15), 2597-2600.
  4. Zhang, Z.F.; Liu, Y.; Lu, L.Y.; Luo, P. Hepatoprotective activity of Gentiana veitchiorum Hemsl. against carbon tetrachloride-induced hepatotoxicity in mice. Chin. J. Nat. Med., 2014, 12(7), 488-494. doi: 10.1016/S1875-5364(14)60076-5 PMID: 25053546
  5. Liang, X.; Tian, Q.; Wei, Z.; Liu, F.; Chen, J.; Zhao, Y.; Qu, P.; Huang, X.; Zhou, X.; Liu, N.; Tian, F.; Tie, R.; Liu, L.; Yu, J. Effect of Feining on bleomycin-induced pulmonary injuries in rats. J. Ethnopharmacol., 2011, 134(3), 971-976. doi: 10.1016/j.jep.2011.02.008 PMID: 21333727
  6. Li, S. Chemical Constituents from Gentiana veitchiorum; Southwest University for Nationalities P.R. China, 2017.
  7. Hou, Y.; Cao, W.; Li, T. Therapeutic effect of Gentiana veitchiorum particles on chronic bronchitis in mice. J. Four. Milit. Med. Uni., 2008, 29(14), 1331-1333.
  8. Li, P.; Tang, J.; Li, A. Experimental Study of Gentiana veitchiorum on DMN-induced Early Liver Fibrosis in Rats. Lishizhen Med. Mat. Med. Res., 2008, 19(07), 1565-1567.
  9. Jansen, P.L.M.; Ghallab, A.; Vartak, N.; Reif, R.; Schaap, F.G.; Hampe, J.; Hengstler, J.G. The ascending pathophysiology of cholestatic liver disease. Hepatology, 2017, 65(2), 722-738. doi: 10.1002/hep.28965 PMID: 27981592
  10. Yang, F.; Wang, Y.; Li, G.; Xue, J.; Chen, Z.L.; Jin, F.; Luo, L.; Zhou, X.; Ma, Q.; Cai, X.; Li, H.R.; Zhao, L. Effects of corilagin on alleviating cholestasis via farnesoid X receptor‐associated pathways in vitro and in vivo. Br. J. Pharmacol., 2018, 175(5), 810-829. doi: 10.1111/bph.14126 PMID: 29235094
  11. Chinese consensus on the diagnosis and management of autoimmune hepatitis (2015). J. Dig. Dis., 2017, 18(5), 247-264. doi: 10.1111/1751-2980.12479 PMID: 28449401
  12. Wagner, M.; Fickert, P. Drug Therapies for Chronic Cholestatic Liver Diseases. Annu. Rev. Pharmacol. Toxicol., 2020, 60(1), 503-527. doi: 10.1146/annurev-pharmtox-010818-021059 PMID: 31506007
  13. Phaw, N.A.; Leighton, J.; Dyson, J.K.; Jones, D.E. Managing cognitive symptoms and fatigue in cholestatic liver disease. Expert Rev. Gastroenterol. Hepatol., 2021, 15(3), 235-241. doi: 10.1080/17474124.2021.1844565 PMID: 33131347
  14. Floreani, A.; Mangini, C. Primary biliary cholangitis: Old and novel therapy. Eur. J. Intern. Med., 2018, 47, 1-5. doi: 10.1016/j.ejim.2017.06.020 PMID: 28669591
  15. Kowdley, K.V.; Luketic, V.; Chapman, R.; Hirschfield, G.M.; Poupon, R.; Schramm, C.; Vincent, C.; Rust, C.; Parés, A.; Mason, A.; Marschall, H.U.; Shapiro, D.; Adorini, L.; Sciacca, C.; Beecher-Jones, T.; Böhm, O.; Pencek, R.; Jones, D.; Obeticholic Acid, P.B.C.M.S.G. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis. Hepatology, 2018, 67(5), 1890-1902. doi: 10.1002/hep.29569 PMID: 29023915
  16. 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. doi: 10.1016/S1875-5364(21)60001-8 PMID: 33516447
  17. Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120. doi: 10.1016/S1875-5364(13)60037-0 PMID: 23787177
  18. Liang, X.; Li, H.; Li, S. A novel network pharmacology approach to analyse traditional herbal formulae: The Liu-Wei-Di-Huang pill as a case study. Mol. Biosyst., 2014, 10(5), 1014-1022. doi: 10.1039/C3MB70507B PMID: 24492828
  19. Lai, X.; Wang, X.; Hu, Y.; Su, S.; Li, W.; Li, S. Editorial: Network pharmacology and traditional medicine. Front. Pharmacol., 2020, 11, 1194. doi: 10.3389/fphar.2020.01194 PMID: 32848794
  20. Zhu, N.; Hou, J. Molecular mechanism of the anti-inflammatory effects of Sophorae Flavescentis Aiton identified by network pharmacology. Sci. Rep., 2021, 11(1), 1005. doi: 10.1038/s41598-020-80297-y PMID: 33441867
  21. Taciak, B. Białasek, M.; Braniewska, A.; Sas, Z.; Sawicka, P.; Kiraga, Ł.; Rygiel, T.; Król, M.; Król, M. Evaluation of phenotypic and functional stability of RAW 264.7 cell line through serial passages. PLoS One, 2018, 13(6), e0198943. doi: 10.1371/journal.pone.0198943 PMID: 29889899
  22. Romerio, A.; Peri, F. Increasing the chemical variety of small-molecule-based TLR4 Modulators: An overview. Front. Immunol., 2020, 11, 1210. doi: 10.3389/fimmu.2020.01210 PMID: 32765484
  23. Martinez, F.O. Regulators of macrophage activation. Eur. J. Immunol., 2011, 41(6), 1531-1534. doi: 10.1002/eji.201141670 PMID: 21607943
  24. Gilbert, F.B.; Cunha, P.; Jensen, K.; Glass, E.J.; Foucras, G.; Robert-Granié, C.; Rupp, R.; Rainard, P. Differential response of bovine mammary epithelial cells to Staphylococcus aureus or Escherichia coli agonists of the innate immune system. Vet. Res., 2013, 44(1), 40. doi: 10.1186/1297-9716-44-40 PMID: 23758654
  25. Komazin, G.; Maybin, M.; Woodard, R.W.; Scior, T.; Schwudke, D.; Schombel, U.; Gisch, N.; Mamat, U.; Meredith, T.C. Substrate structure-activity relationship reveals a limited lipopolysaccharide chemotype range for intestinal alkaline phosphatase. J. Biol. Chem., 2019, 294(50), 19405-19423. doi: 10.1074/jbc.RA119.010836 PMID: 31704704
  26. Stifano, G.; Affandi, A.J.; Mathes, A.L.; Rice, L.M.; Nakerakanti, S.; Nazari, B.; Lee, J.; Christmann, R.B.; Lafyatis, R. Chronic Toll-like receptor 4 stimulation in skin induces inflammation, macrophage activation, transforming growth factor beta signature gene expression, and fibrosis. Arthritis Res. Ther., 2014, 16(4), R136. doi: 10.1186/ar4598 PMID: 24984848
  27. Wang, M.; Liu, F.; Yao, Y.; Zhang, Q.; Lu, Z.; Zhang, R.; Liu, C.; Lin, C.; Zhu, C. Network pharmacology-based mechanism prediction and pharmacological validation of Xiaoyan Lidan formula on attenuating alpha-naphthylisothiocyanate induced cholestatic hepatic injury in rats. J. Ethnopharmacol., 2021, 270, 113816. doi: 10.1016/j.jep.2021.113816 PMID: 33444723
  28. Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461. doi: 10.1002/jcc.21334 PMID: 19499576
  29. Yuan, H-Y.; Kwaku, O.R.; Pan, H.; Han, J-X.; Yang, C-R.; Xu, M.J.N.P.C. Iridoid glycosides from the genus gentiana (Gentianaceae) and their chemotaxonomic sense. Nat. Prod. Commun., 2017, 12(10), 1663-1670.
  30. Liang, X.; Ji, S.; Du, S.; Dong, Z.; Chen, X. Analysis of chemical constituents in different parts of gentiana straminea based on UPLC-Q-TOF-MS/MS. Chi. J. Exper. Trad. Med. For., 2022, 28(08), 139-148.
  31. Suryawanshi, S.; Mehrotra, N.; Asthana, R.K.; Gupta, R.C. Liquid chromatography/tandem mass spectrometric study and analysis of xanthone and secoiridoid glycoside composition of Swertia chirata, a potent antidiabetic. Rapid Commun. Mass Spectrom., 2006, 20(24), 3761-3768. doi: 10.1002/rcm.2795 PMID: 17120271
  32. Bianco, A.; Passacantilli, P.; Polidori, G. 8-epiloganic acid and 7-beta-hydroxy-8-epiiridodial glucoside. Planta Med., 1982, 46(9), 38-41. doi: 10.1055/s-2007-970014 PMID: 17396936
  33. Olennikov, D.N.; Chirikova, N.K. Algidisides I and II, New Iridoid Glycosides from Gentiana algida. Chem. Nat. Compd., 2016, 52(4), 637-641. doi: 10.1007/s10600-016-1728-y
  34. Kikuchi, M.; Kakuda, R.; Kikuchi, M.; Yaoita, Y. Secoiridoid Glycosides from Gentiana scabra. J. Nat. Prod., 2005, 68(5), 751-753. doi: 10.1021/np058017o PMID: 15921422
  35. Tan, P.; Liu, Y.; Hou, C. Structure of purplish bitter glycosides in purple red swertia. Yao Xue Xue Bao, 1997, (07), 522-525.
  36. Andrzejewska-Golec, E. Ofterdinger-Daegel, S.; Calis, I.; Światek, L. Chemotaxonomic aspects of iridoids occurring inPlantago subg. Psyllium (Plantaginaceae). Plant Syst. Evol., 1993, 185(1-2), 85-89. doi: 10.1007/BF00937721
  37. Wu, X.; Du, M. Rule of ESIMS-MS on C-glycosy flavonnes. Nat. Prod. Res. Devel., 2011, 23(06), 1085-1087.
  38. Sasaki, N.; Nishizaki, Y.; Yamada, E.; Tatsuzawa, F.; Nakatsuka, T.; Takahashi, H.; Nishihara, M. Identification of the glucosyltransferase that mediates direct flavone C ‐glucosylation in Gentiana triflora. FEBS Lett., 2015, 589(1), 182-187. doi: 10.1016/j.febslet.2014.11.045 PMID: 25479084
  39. Schaufelberger, D.; Hostettmann, K. High-performance liquid chromatographic analysis of secoiridoid flavone glycosides in closely related Gentiana species. J. Chromatogr. A, 1987, 389, 450-455. doi: 10.1016/S0021-9673(01)94458-9
  40. Huang, M.; Zhang, Y.; Xu, S.; Xu, W.; Chu, K.; Xu, W.; Zhao, H.; Lu, J. Identification and quantification of phenolic compounds in Vitex negundo L. var. cannabifolia (Siebold et Zucc.) Hand.-Mazz. using liquid chromatography combined with quadrupole time-of-flight and triple quadrupole mass spectrometers. J. Pharm. Biomed. Anal., 2015, 108, 11-20. doi: 10.1016/j.jpba.2015.01.049 PMID: 25703235
  41. Bergeron, C.; Marston, A.; Gauthier, R.; Hostettmann, K. Iridoids and secoiridoids from Gentiana linearis. Phytochemistry, 1997, 44(4), 633-637. doi: 10.1016/S0031-9422(96)00636-X
  42. Pasdaran, A.; Butovska, D.; Kerr, P.; Naychov, Z.; Aneva, I.; Kozuharova, E. Gentians, natural remedies for future of visceral pain control; an ethnopharmacological review with an in silico approach. Biologia Futura, 2022, 73(2), 219-227. doi: 10.1007/s42977-022-00114-7 PMID: 35318616
  43. Xu, H.; Liu, T.; Wang, W.; Su, N.; Yang, L.; Yang, Z.; Dou, F.; Cui, J.; Fei, F.; Ma, J.; Wen, A.; Ding, Y. Proteomic analysis of hydroxysafflor yellow a against cerebral ischemia/reperfusion injury in rats. Rejuvenation Res., 2019, 22(6), 503-512. doi: 10.1089/rej.2018.2145 PMID: 30712471
  44. Schmidt, S.; Gonzalez, D.; Derendorf, H. Significance of protein binding in pharmacokinetics and pharmacodynamics. J. Pharm. Sci., 2010, 99(3), 1107-1122. doi: 10.1002/jps.21916 PMID: 19852037
  45. van Golen, R.F.; Olthof, P.B.; de Haan, L.R.; Coelen, R.J.; Pechlivanis, A.; de Keijzer, M.J.; Weijer, R.; de Waart, D.R.; van Kuilenburg, A.B.P.; Roelofsen, J.; Gilijamse, P.W.; Maas, M.A.; Lewis, M.R.; Nicholson, J.K.; Verheij, J.; Heger, M. The pathophysiology of human obstructive cholestasis is mimicked in cholestatic Gold Syrian hamsters. Biochim. Biophys. Acta Mol. Basis Dis., 2018, 1864(3), 942-951. doi: 10.1016/j.bbadis.2017.11.022 PMID: 29196240
  46. Mariotti, V.; Strazzabosco, M.; Fabris, L.; Calvisi, D.F. Animal models of biliary injury and altered bile acid metabolism. Biochim. Biophys. Acta Mol. Basis Dis., 2018, 1864(4)(4 Pt B), 1254-1261. doi: 10.1016/j.bbadis.2017.06.027 PMID: 28709963
  47. Ghonem, N.S.; Assis, D.N.; Boyer, J.L. Fibrates and cholestasis. Hepatology, 2015, 62(2), 635-643. doi: 10.1002/hep.27744 PMID: 25678132
  48. Dou, X.; Zhou, Z.; Ren, R.; Xu, M. Apigenin, flavonoid component isolated from Gentiana veitchiorum flower suppresses the oxidative stress through LDLR-LCAT signaling pathway. Biomed. Pharmacother., 2020, 128, 110298. doi: 10.1016/j.biopha.2020.110298 PMID: 32504920
  49. Yang, H.P.; Que, S.; Wu, X.D.; Shi, Y.P. Studies on glycosides from Gentiana veitchiorum. Zhongguo Zhongyao Zazhi, 2008, 33(21), 2505-2507. PMID: 19149260
  50. Cui, X-R.; Zheng, G-H.; Nan, J-X. Protective effects of Gentiana manshurica on liver injury. J. Med. Sci. Yanb. Uni., 2004, 27(03), 170-172.
  51. Jiang, W-X.; Xue, B-Y. Hepatoprotective effects of Gentiana scabra on the acute liver injuries in mice. Zhongguo Zhongyao Zazhi, 2005, 30(14), 1105-1107. PMID: 16161450
  52. Zhao, J.; Xu, J.; Xu, Y.; Chen, S.; Guo, Y.; Gao, Q.; Sun, G. High-throughput metabolomics method for discovering metabolic biomarkers and pathways to reveal effects and molecular mechanism of ethanol extract from epimedium against osteoporosis. Front. Pharmacol., 2020, 11, 1318. doi: 10.3389/fphar.2020.01318 PMID: 32973531
  53. Li, S.; Zhao, Y.; Liu, Y.; Zhang, Z. Separation and preparation of three compounds from Gentiana veitchiorum by high-speed counter-current chromatography (HSCCC). J. South. Uni. Nat., 2016, 42(06), 660-664.
  54. Zou, Q.; Liang, J.; Liao, X.; Peng, S.; Ding, L. Chemical constituents from the whole plants of Gentiana veitchiorum. West Chi. J. Pharma. Sci., 2010, 25(02), 512-514.
  55. Cao, H.; Zhao, Z.; Ga, W. Research progress of Tibetan medicine Gentiana veitchiorum. West Chi. J. Pharma. Sci., 2014, 37(06), 1087-1093.
  56. Ma, X.; Jiang, Y.; Zhang, W.; Wang, J.; Wang, R.; Wang, L.; Wei, S.; Wen, J.; Li, H.; Zhao, Y. Natural products for the prevention and treatment of cholestasis: A review. Phytother. Res., 2020, 34(6), 1291-1309. doi: 10.1002/ptr.6621 PMID: 32026542
  57. Han, H.; Xu, L.; Xiong, K.; Zhang, T.; Wang, Z. Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures. Cell. Physiol. Biochem., 2018, 49(4), 1304-1319. doi: 10.1159/000493409 PMID: 30223280
  58. Qi, M.; Liu, K.; He, J. Alleviation effect of ginsenoside Rg1 in rats with cholestasis by sirt5 pathway. China Pharmacist., 2022, 25(10), 1718-1723.
  59. Shi, M.; Tang, J.; Zhang, T.; Han, H. Swertiamarin, an active iridoid glycoside from Swertia pseudochinensis H. Hara, protects against alpha-naphthylisothiocyanate-induced cholestasis by activating the farnesoid X receptor and bile acid excretion pathway. J. Ethnopharmacol., 2022, 291, 115164. doi: 10.1016/j.jep.2022.115164 PMID: 35278607
  60. Wang, L.; Wu, G.; Wu, F.; Jiang, N.; Lin, Y. Geniposide attenuates ANIT-induced cholestasis through regulation of transporters and enzymes involved in bile acids homeostasis in rats. J. Ethnopharmacol., 2017, 196, 178-185. doi: 10.1016/j.jep.2016.12.022 PMID: 27988401
  61. Xiang, J.; Yang, G.; Ma, C.; Wei, L.; Wu, H.; Zhang, W.; Tao, X.; Jiang, L.; Liang, Z.; Kang, L.; Yang, S. Tectorigenin alleviates intrahepatic cholestasis by inhibiting hepatic inflammation and bile accumulation via activation of PPARγ. Br. J. Pharmacol., 2021, 178(12), 2443-2460. doi: 10.1111/bph.15429 PMID: 33661551
  62. Zhang, G.; Sun, X.; Wen, Y.; Shi, A.; Zhang, J.; Wei, Y.; Wu, X. Hesperidin alleviates cholestasis via activation of the farnesoid X receptor in vitro and in vivo. Eur. J. Pharmacol., 2020, 885, 173498. doi: 10.1016/j.ejphar.2020.173498 PMID: 32841642
  63. Li, S.; Wang, R.; Wu, B.; Wang, Y.; Song, F.; Gu, Y.; Yuan, Y. Salvianolic acid B protects against ANIT-induced cholestatic liver injury through regulating bile acid transporters and enzymes, and NF-κB/IκB and MAPK pathways. Naunyn Schmiedebergs Arch. Pharmacol., 2019, 392(9), 1169-1180. doi: 10.1007/s00210-019-01657-8 PMID: 31098695
  64. Facchin, B.M.; dos Reis, G.O.; Vieira, G.N.; Mohr, E.T.B.; da Rosa, J.S.; Kretzer, I.F.; Demarchi, I.G.; Dalmarco, E.M. Inflammatory biomarkers on an LPS-induced RAW 264.7 cell model: A systematic review and meta-analysis. Inflamm. Res., 2022, 71(7-8), 741-758. doi: 10.1007/s00011-022-01584-0 PMID: 35612604
  65. Elisia, I.; Pae, H.B.; Lam, V.; Cederberg, R.; Hofs, E.; Krystal, G. Comparison of RAW264.7, human whole blood and PBMC assays to screen for immunomodulators. J. Immunol. Methods, 2018, 452, 26-31. doi: 10.1016/j.jim.2017.10.004 PMID: 29042255
  66. Dhingra, S.; Sharma, A.K.; Singla, D.K.; Singal, P.K. p38 and ERK1/2 MAPKs mediate the interplay of TNF-α and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis. Am. J. Physiol. Heart Circ. Physiol., 2007, 293(6), H3524-H3531. doi: 10.1152/ajpheart.00919.2007 PMID: 17906102
  67. Yang, X.; Feng, Y.; Liu, Y.; Ye, X.; Ji, X.; Sun, L.; Gao, F.; Zhang, Q.; Li, Y.; Zhu, B.; Wang, X. Fuzheng Jiedu Xiaoji formulation inhibits hepatocellular carcinoma progression in patients by targeting the AKT/CyclinD1/p21/p27 pathway. Phytomedicine, 2021, 87, 153575. doi: 10.1016/j.phymed.2021.153575 PMID: 33984593
  68. Kassouf, T.; Sumara, G. Impact of conventional and atypical MAPKs on the development of metabolic diseases. Biomolecules, 2020, 10(9), 1256. doi: 10.3390/biom10091256 PMID: 32872540
  69. You, L.P.; Wang, K.X.; Lin, J.C.; Ren, X.Y.; Wei, Y.; Li, W.X.; Gao, Y.Q.; Kong, X.N.; Sun, X.H. Yin-chen Wu-ling powder alleviate cholestatic liver disease: Network pharmacological analysis and experimental validation. Gene, 2023, 851, 146973. doi: 10.1016/j.gene.2022.146973 PMID: 36306943
  70. Wang, J.; Wen, J.; Ma, X.; Yang, J.; Zhang, Z.; Xie, S.; Wei, S.; Jing, M.; Li, H.; Lang, L.; Zhou, X.; Zhao, Y. Validation of MAPK signalling pathway as a key role of paeoniflorin in the treatment of intrahepatic cholestasis of pregnancy based on network pharmacology and metabolomics. Eur. J. Pharmacol., 2022, 935, 175331. doi: 10.1016/j.ejphar.2022.175331 PMID: 36273619
  71. Ma, X.; Zhao, Y.L.; Zhu, Y.; Chen, Z.; Wang, J.B.; Li, R.Y.; Chen, C.; Wei, S.Z.; Li, J.Y.; Liu, B.; Wang, R.L.; Li, Y.G.; Wang, L.F.; Xiao, X.H. Paeonia lactiflora Pall. Protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway. Drug Des. Devel. Ther., 2015, 9, 5061-5074. PMID: 26366057
  72. Ma, X.; Wen, J.X.; Gao, S.J.; He, X.; Li, P.Y.; Yang, Y.X.; Wei, S.; Zhao, Y.L.; Xiao, X.H. Paeonia lactiflora Pall. Regulates the NF-κB-NLRP3 inflammasome pathway to alleviate cholestasis in rats. J. Pharm. Pharmacol., 2018, 70(12), 1675-1687. doi: 10.1111/jphp.13008 PMID: 30277564
  73. Yao, H. Protective effects and mechanisms of dioscin on liver injury; Dalian Medical University, 2017. doi: 10.26994/d.cnki.gdlyu.2017.000294
  74. Yang, R. Effect of Pes1 on mice with cholestatic liver disease via PI3K/AKT/GSK-3β signaling pathway. Anhui Med. Uni., 2019, 54(10), 1511-1515.
  75. Hua, W.; Zhang, S.; Lu, Q.; Sun, Y.; Tan, S.; Chen, F.; Tang, L. Protective effects of n-Butanol extract and iridoid glycosides of Veronica ciliata Fisch. Against ANIT-induced cholestatic liver injury in mice. J. Ethnopharmacol., 2021, 266, 113432. doi: 10.1016/j.jep.2020.113432 PMID: 33011367
  76. Nabih, E.S.; El-kharashi, O.A. Targeting HMGB1/TLR4 axis and miR-21 by rosuvastatin: role in alleviating cholestatic liver injury in a rat model of bile duct ligation. Naunyn Schmiedebergs Arch. Pharmacol., 2019, 392(1), 37-43. doi: 10.1007/s00210-018-1560-y PMID: 30203151
  77. Liu, B.; Zhang, J.; Shao, L.; Yao, J. Network pharmacology analysis and molecular docking to unveil the potential mechanisms of San-Huang-Chai-Zhu formula treating cholestasis. PLoS One, 2022, 17(2), e0264398. doi: 10.1371/journal.pone.0264398 PMID: 35196362
  78. Cuadrado, A.; Nebreda, A.R. Mechanisms and functions of p38 MAPK signalling. Biochem. J., 2010, 429(3), 403-417. doi: 10.1042/BJ20100323 PMID: 20626350
  79. Tomida, T.; Takekawa, M.; Saito, H. Oscillation of p38 activity controls efficient pro-inflammatory gene expression. Nat. Commun., 2015, 6(1), 8350. doi: 10.1038/ncomms9350 PMID: 26399197
  80. Yang, Q.; Yang, F.; Gong, J.; Tang, X.; Wang, G.; Wang, Z.; Yang, L. Sweroside ameliorates α-naphthylisothiocyanate-induced cholestatic liver injury in mice by regulating bile acids and suppressing pro-inflammatory responses. Acta Pharmacol. Sin., 2016, 37(9), 1218-1228. doi: 10.1038/aps.2016.86 PMID: 27498779
  81. Liu, S.; Zhang, X.; Wang, J. Isovitexin protects against cisplatin-induced kidney injury in mice through inhibiting inflammatory and oxidative responses. Int. Immunopharmacol., 2020, 83, 106437. doi: 10.1016/j.intimp.2020.106437 PMID: 32222637
  82. Wan, Z.; Li, H.; Wu, X.; Zhao, H.; Wang, R.; Li, M.; Liu, J.; Liu, Q.; Wang, R.; Li, X. Hepatoprotective effect of gentiopicroside in combination with leflunomide and/or methotrexate in arthritic rats. Life Sci., 2021, 265, 118689. doi: 10.1016/j.lfs.2020.118689 PMID: 33130083
  83. Wei, X.; Fan, X.; Feng, Z.; Ma, Y.; Lan, X.; Chen, M. Ethyl acetate extract of herpetospermum pedunculosum alleviates α-naphthylisothiocyanate-induced cholestasis by activating the farnesoid x receptor and suppressing oxidative stress and inflammation in rats. Phytomedicine, 2020, 76, 153257. doi: 10.1016/j.phymed.2020.153257 PMID: 32534360
  84. Yan, M.; Guo, L.; Yang, Y.; Zhang, B.; Hou, Z.; Gao, Y.; Gu, H.; Gong, H. Glycyrrhetinic acid protects α-naphthylisothiocyanate- induced cholestasis through regulating transporters, inflammation and apoptosis. Front. Pharmacol., 2021, 12, 701240. doi: 10.3389/fphar.2021.701240 PMID: 34630081
  85. Wang, Y.; Fang, J.; Liu, B.; Shao, C.; Shi, Y. Reciprocal regulation of mesenchymal stem cells and immune responses. Cell Stem Cell, 2022, 29(11), 1515-1530. doi: 10.1016/j.stem.2022.10.001 PMID: 36332569
  86. Appleton, I.; Tomlinson, A.; Willoughby, D.A. Induction of Cyclo-oxygenase and Nitric Oxide Synthase in Inflammation. Adv. Pharmacl., 1996, 35, 27-78. doi: 10.1016/S1054-3589(08)60274-4
  87. Hamza, A.R.; Krasniqi, A.S.; Srinivasan, P.K.; Afify, M.; Bleilevens, C.; Klinge, U.; Tolba, R.H. Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection. World J. Gastroenterol., 2014, 20(40), 14841-14854. doi: 10.3748/wjg.v20.i40.14841 PMID: 25356044
  88. Cao, F.; Liu, P.; Zhang, X.; Hu, Y.; Dong, X.; Bao, H.; Kong, L.; Wang, L.; Gong, P. Shenqi fuzheng injection impairs bile duct ligation-induced cholestatic liver injury in vivo. Biosci. Rep., 2019, 39(1), BSR20180787. doi: 10.1042/BSR20180787 PMID: 30610157
  89. Kim, S.M.; Park, K.C.; Kim, H.G.; Han, S.J. Effect of selective cyclooxygenase‐2 inhibitor meloxicam on liver fibrosis in rats with ligated common bile ducts. Hepatol. Res., 2008, 38(8), 800-809. doi: 10.1111/j.1872-034X.2008.00339.x PMID: 18462380
  90. Luan, X.; Chen, P.; Li, Y.; Yuan, X.; Miao, L.; Zhang, P.; Cao, Q.; Song, X.; Di, G. TNF-α/IL-1β-licensed hADSCs alleviate cholestatic liver injury and fibrosis in mice via COX-2/PGE2 pathway. Stem Cell Res. Ther., 2023, 14(1), 100. doi: 10.1186/s13287-023-03342-3 PMID: 37095581
  91. Voo, K.S.; Wang, Y.H.; Santori, F.R.; Boggiano, C.; Wang, Y.H.; Arima, K.; Bover, L.; Hanabuchi, S.; Khalili, J.; Marinova, E.; Zheng, B.; Littman, D.R.; Liu, Y.J. Identification of IL-17-producing FOXP3 + regulatory T cells in humans. Proc. Natl. Acad. Sci., 2009, 106(12), 4793-4798. doi: 10.1073/pnas.0900408106 PMID: 19273860
  92. Tan, Z.; Qian, X.; Jiang, R.; Liu, Q.; Wang, Y.; Chen, C.; Wang, X.; Ryffel, B.; Sun, B. IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation. J. Immunol., 2013, 191(4), 1835-1844. doi: 10.4049/jimmunol.1203013 PMID: 23842754
  93. Meng, F.; Wang, K.; Aoyama, T.; Grivennikov, S.I.; Paik, Y.; Scholten, D.; Cong, M.; Iwaisako, K.; Liu, X.; Zhang, M.; Österreicher, C.H.; Stickel, F.; Ley, K.; Brenner, D.A.; Kisseleva, T. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology, 2012, 143(3), 765-776.e3. doi: 10.1053/j.gastro.2012.05.049 PMID: 22687286
  94. Qian, C.; Jiang, T.; Zhang, W.; Ren, C.; Wang, Q.; Qin, Q.; Chen, J.; Deng, A.; Zhong, R. Increased IL-23 and IL-17 expression by peripheral blood cells of patients with primary biliary cirrhosis. Cytokine, 2013, 64(1), 172-180. doi: 10.1016/j.cyto.2013.07.005 PMID: 23910013
  95. O’Brien, K.M.; Allen, K.M.; Rockwell, C.E.; Towery, K.; Luyendyk, J.P.; Copple, B.L. IL-17A synergistically enhances bile acid-induced inflammation during obstructive cholestasis. Am. J. Pathol., 2013, 183(5), 1498-1507. doi: 10.1016/j.ajpath.2013.07.019 PMID: 24012680
  96. Zhang, S.; Huang, D.; Weng, J.; Huang, Y.; Liu, S.; Zhang, Q.; Li, N.; Wen, M.; Zhu, G.; Lin, F.; Gu, W. Neutralization of interleukin‐17 attenuates cholestatic liver fibrosis in mice. Scand. J. Immunol., 2016, 83(2), 102-108. doi: 10.1111/sji.12395 PMID: 26484852

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