Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Network Pharmacology, Molecular Docking Analysis and Molecular Dynamics Simulation of Scutellaria baicalensis in the Treatment of Liver Fibrosis

Author(s): Junrui Wang, Zhuoqing Wu, Xiaolei Chen, Ying Sun, Shuyao Ma, Jingdan Weng, Yuxin Zhang, Keke Dong, Jiangjuan Shao* and Shizhong Zheng*

Volume 30, Issue 17, 2024

Published on: 08 April, 2024

Page: [1326 - 1340] Pages: 15

DOI: 10.2174/0113816128297074240327090020

Price: $65

Abstract

Background: Traditional Chinese medicine Scutellaria Baicalensis (SB), one of the clinical firstline heat-clearing drugs, has obvious symptomatic advantages for hepatic fibrosis with dampness-heat stasis as its syndrome. We aim to predict and validate the potential mechanism of Scutellaria baicalensis active ingredients against liver fibrosis more scientifically and effectively.

Methods: The underlying mechanism of Scutellaria baicalensis in inhibiting hepatic fibrosis was studied by applying network pharmacology, molecular docking and molecular dynamics simulation. Expression levels of markers in activated Hepatic Stellate Cells (HSC) after administration of three Scutellaria baicalensis extracts were determined by Western blot and Real-time PCR, respectively, in order to verify the anti-fibrosis effect of the active ingredients

Results: There are 164 common targets of drugs and diseases screened and 115 signaling pathways obtained, which were mainly associated with protein phosphorylation, senescence and negative regulation of the apoptotic process. Western blot and Real-time PCR showed that Scutellaria baicalensis extracts could reduce the expression of HSC activation markers, and Oroxylin A had the strongest inhibitory effect on it. Molecular docking results showed that Oroxylin A had high binding activity to target proteins. Molecular dynamics simulation demonstrates promising stability of the Oroxylin A-AKT1 complex over the simulated MD time of 200 ns.

Conclusion: Scutellaria baicalensis active ingredients may inhibit HSC proliferation, reduce the generation of pro-inflammatory factors and block the anti-inflammatory effect of inflammatory signal transduction by inducing HSC apoptosis and senescence, thus achieving the effect of anti-fibrosis.

[1]
Friedman SL. Liver fibrosis - From bench to bedside. J Hepatol 2003; 38 (Suppl. 1): 38-53.
[http://dx.doi.org/10.1016/S0168-8278(02)00429-4] [PMID: 12591185]
[2]
Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115(2): 209-18.
[http://dx.doi.org/10.1172/JCI24282] [PMID: 15690074]
[3]
Hammerich L, Tacke F. Hepatic inflammatory responses in liver fibrosis. Nat Rev Gastroenterol Hepatol 2023; 20(10): 633-46.
[http://dx.doi.org/10.1038/s41575-023-00807-x] [PMID: 37400694]
[4]
Higashi T, Friedman SL, Hoshida Y. Hepatic stellate cells as key target in liver fibrosis. Adv Drug Deliv Rev 2017; 121: 27-42.
[http://dx.doi.org/10.1016/j.addr.2017.05.007] [PMID: 28506744]
[5]
Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol 2021; 18(3): 151-66.
[http://dx.doi.org/10.1038/s41575-020-00372-7] [PMID: 33128017]
[6]
Parola M, Pinzani M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. Mol Aspects Med 2019; 65: 37-55.
[http://dx.doi.org/10.1016/j.mam.2018.09.002] [PMID: 30213667]
[7]
Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO. Liver fibrosis: Direct antifibrotic agents and targeted therapies. Matrix Biol 2018; 68-69: 435-51.
[http://dx.doi.org/10.1016/j.matbio.2018.04.006] [PMID: 29656147]
[8]
Poynard T, Ratziu V, Benhamou Y, Opolon P, Cacoub P, Bedossa P. Natural history of HCV infection. Best Pract Res Clin Gastroenterol 2000; 14(2): 211-28.
[http://dx.doi.org/10.1053/bega.1999.0071] [PMID: 10890317]
[9]
Sun M, Kisseleva T. Reversibility of liver fibrosis. Clin Res Hepatol Gastroenterol 2015; 39(1): S60-3.
[http://dx.doi.org/10.1016/j.clinre.2015.06.015]
[10]
Bansal MB, Chamroonkul N. Antifibrotics in liver disease: Are we getting closer to clinical use? Hepatol Int 2019; 13(1): 25-39.
[http://dx.doi.org/10.1007/s12072-018-9897-3] [PMID: 30302735]
[11]
Roehlen N, Crouchet E, Baumert TF. Liver fibrosis: Mechanistic concepts and therapeutic perspectives. Cells 2020; 9(4): 875.
[http://dx.doi.org/10.3390/cells9040875] [PMID: 32260126]
[12]
Zhao T, Tang H, Xie L, et al. Scutellaria baicalensis Georgi. (Lamiaceae): A review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. J Pharm Pharmacol 2019; 71(9): 1353-69.
[http://dx.doi.org/10.1111/jphp.13129] [PMID: 31236960]
[13]
Ganguly R, Gupta A, Pandey AK. Role of baicalin as a potential therapeutic agent in hepatobiliary and gastrointestinal disorders: A review. World J Gastroenterol 2022; 28(26): 3047-62.
[http://dx.doi.org/10.3748/wjg.v28.i26.3047] [PMID: 36051349]
[14]
Huang Q, Wang M, Wang M, et al. Scutellaria baicalensis: A promising natural source of antiviral compounds for the treatment of viral diseases. Chin J Nat Med 2023; 21(8): 563-75.
[http://dx.doi.org/10.1016/S1875-5364(23)60401-7] [PMID: 37611975]
[15]
Zhang M, Song Y, Xu W, Zhang L, Li C, Li Y. Natural herbal medicine as a treatment strategy for myocardial infarction through the regulation of angiogenesis. Evid Based Complement Alternat Med 2022; 2022: 1-17.
[http://dx.doi.org/10.1155/2022/8831750] [PMID: 35600953]
[16]
Zhou X, Fu L, Wang P, Yang L, Zhu X, Li CG. Drug-herb interactions between Scutellaria baicalensis and pharmaceutical drugs: Insights from experimental studies, mechanistic actions to clinical applications. Biomed Pharmacother 2021; 138: 111445.
[http://dx.doi.org/10.1016/j.biopha.2021.111445] [PMID: 33711551]
[17]
Bai QY, Tao SM, Tian JH, Cao CR. Progress of research on effect and mechanism of Scutellariae radix on preventing liver diseases. Zhongguo Zhongyao Zazhi 2020; 45(12): 2808-16.
[PMID: 32627454]
[18]
Guo X, Zheng B, Wang J, Zhao T, Zheng Y. Exploring the mechanism of action of Chinese medicine in regulating liver fibrosis based on the alteration of glucose metabolic pathways. Phytother Res 2022; ptr.7667.
[http://dx.doi.org/10.1002/ptr.7667] [PMID: 36433866]
[19]
Nan JX, Park EJ, Kim YC, Ko G, Sohn DH. Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or carbon tetrachloride in rats. J Pharm Pharmacol 2010; 54(4): 555-63.
[http://dx.doi.org/10.1211/0022357021778673] [PMID: 11999134]
[20]
Pan TL, Wang PW, Leu YL, Wu TH, Wu TS. Inhibitory effects of Scutellaria baicalensis extract on hepatic stellate cells through inducing G2/M cell cycle arrest and activating ERK-dependent apoptosis via Bax and caspase pathway. J Ethnopharmacol 2012; 139(3): 829-37.
[http://dx.doi.org/10.1016/j.jep.2011.12.028] [PMID: 22210104]
[21]
Wang ZL, Wang S, Kuang Y, Hu ZM, Qiao X, Ye M. A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis. Pharm Biol 2018; 56(1): 465-84.
[http://dx.doi.org/10.1080/13880209.2018.1492620] [PMID: 31070530]
[22]
De Vivo M, Masetti M, Bottegoni G, Cavalli A. Role of molecular dynamics and related methods in drug discovery. J Med Chem 2016; 59(9): 4035-61.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01684] [PMID: 26807648]
[23]
Decherchi S, Cavalli A. Thermodynamics and kinetics of drug-target binding by molecular simulation. Chem Rev 2020; 120(23): 12788-833.
[http://dx.doi.org/10.1021/acs.chemrev.0c00534] [PMID: 33006893]
[24]
Do PC, Lee EH, Le L. Steered molecular dynamics simulation in rational drug design. J Chem Inf Model 2018; 58(8): 1473-82.
[http://dx.doi.org/10.1021/acs.jcim.8b00261] [PMID: 29975531]
[25]
Guruge AG, Warren DB, Pouton CW, Chalmers DK. Molecular dynamics simulation studies of bile, bile salts, lipid-based drug formulations, and mRNA-lipid nanoparticles: A review. Mol Pharm 2023; 20(6): 2781-800.
[http://dx.doi.org/10.1021/acs.molpharmaceut.3c00049] [PMID: 37194978]
[26]
Lundborg M, Wennberg CL, Narangifard A, Lindahl E, Norlén L. Predicting drug permeability through skin using molecular dynamics simulation. J Control Release 2018; 283: 269-79.
[http://dx.doi.org/10.1016/j.jconrel.2018.05.026] [PMID: 29864475]
[27]
Milardi D, Pappalardo M. Molecular dynamics: New advances in drug discovery. Eur J Med Chem 2015; 91: 1-3.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.078] [PMID: 25466447]
[28]
Ru J, Li P, Wang J, et al. 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]
[29]
Liu Y, Yu L, Zhang J, Xie D, Zhang X, Yu J. Network pharmacology-based and molecular docking-based analysis of Suanzaoren decoction for the treatment of Parkinson’s disease with sleep disorder. BioMed Res Int 2021; 2021: 1-12.
[http://dx.doi.org/10.1155/2021/1752570] [PMID: 34660782]
[30]
Daina A, Michielin O, Zoete V. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res 2019; 47(W1): W357-64.
[http://dx.doi.org/10.1093/nar/gkz382] [PMID: 31106366]
[31]
Bateman A, Martin M-J, Orchard S, et al. UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res 2021; 49(D1): D480-9.
[http://dx.doi.org/10.1093/nar/gkaa1100] [PMID: 33237286]
[32]
Hong YAO, Jin-hong REN, Yu-xin HOU, Yu-xuan WANG, Hui-qing XUE. Study on the mechanism of Astragalus radix against liver cancer based on network pharmacology and molecular docking. Nat Prod Res Dev 2021; 33(06): 1020-31.
[33]
Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: The human gene integrator. Database (Oxford) 2010; 2010(0): baq020.
[http://dx.doi.org/10.1093/database/baq020] [PMID: 20689021]
[34]
Li X, Wei S, Niu S, et al. Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Huanglian Jiedu decoction against sepsis. Comput Biol Med 2022; 144: 105389.
[http://dx.doi.org/10.1016/j.compbiomed.2022.105389] [PMID: 35303581]
[35]
Shannon P, Markiel A, Ozier O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13(11): 2498-504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[36]
Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019; 47(D1): D607-13.
[http://dx.doi.org/10.1093/nar/gky1131] [PMID: 30476243]
[37]
Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4(1): 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[38]
Tang D, Chen M, Huang X, et al. SRplot: A free online platform for data visualization and graphing. PLoS One 2023; 18(11): e0294236.
[http://dx.doi.org/10.1371/journal.pone.0294236] [PMID: 37943830]
[39]
Hess B, Kutzner C, van der Spoel D, Lindahl E. GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 2008; 4(3): 435-47.
[http://dx.doi.org/10.1021/ct700301q] [PMID: 26620784]
[40]
Humphrey W, Dalke A, Schulten K. VMD: Visual molecular dynamics. J Mol Graph 1996; 14(1): 33-38 .
[http://dx.doi.org/10.1016/0263-7855(96)00018-5]
[41]
Pirojsirikul T, Lee VS, Nimmanpipug P. Unraveling bacterial single-stranded sequence specificities: Insights from molecular dynamics and MMPBSA analysis of oligonucleotide probes. Mol Biotechnol 2024.
[http://dx.doi.org/10.1007/s12033-024-01082-0] [PMID: 38374320]
[42]
Chong LT, Pitera JW, Swope WC, Pande VS. Comparison of computational approaches for predicting the effects of missense mutations on p53 function. J Mol Graph Model 2009; 27(8): 978-82.
[http://dx.doi.org/10.1016/j.jmgm.2008.12.006] [PMID: 19168381]
[43]
Genheden S, Ryde U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov 2015; 10(5): 449-61.
[http://dx.doi.org/10.1517/17460441.2015.1032936] [PMID: 25835573]
[44]
Sun Y, Weng J, Chen X, et al. Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway. Biomed Pharmacother 2023; 162: 114653.
[http://dx.doi.org/10.1016/j.biopha.2023.114653] [PMID: 37086511]
[45]
Zhao D, Gao Y, Su Y, et al. Oroxylin A regulates cGAS DNA hypermethylation induced by methionine metabolism to promote HSC senescence. Pharmacol Res 2023; 187: 106590.
[http://dx.doi.org/10.1016/j.phrs.2022.106590] [PMID: 36464146]
[46]
Cai X, Wang J, Wang J, et al. Intercellular crosstalk of hepatic stellate cells in liver fibrosis: New insights into therapy. Pharmacol Res 2020; 155: 104720.
[http://dx.doi.org/10.1016/j.phrs.2020.104720] [PMID: 32092405]
[47]
Parola M, Pinzani M. Liver fibrosis in NAFLD/NASH: From pathophysiology towards diagnostic and therapeutic strategies. Mol Aspects Med 2024; 95: 101231.
[http://dx.doi.org/10.1016/j.mam.2023.101231] [PMID: 38056058]
[48]
Wang F, Li Z, Chen L, et al. Inhibition of ASCT2 induces hepatic stellate cell senescence with modified proinflammatory secretome through an IL-1α/NF-κB feedback pathway to inhibit liver fibrosis. Acta Pharm Sin B 2022; 12(9): 3618-38.
[http://dx.doi.org/10.1016/j.apsb.2022.03.014] [PMID: 36176909]
[49]
Tiainen P, Pasanen A, Sormunen R, Myllyharju J. Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an enzyme modifying the basement membrane collagen IV. J Biol Chem 2008; 283(28): 19432-9.
[http://dx.doi.org/10.1074/jbc.M802973200] [PMID: 18487197]
[50]
Yang ZONG, Ding M, Ke-Ke JIA, Shi-tang MA, Ju W. Exploring active compounds of Da-Yuan-Yin in treatment of COVID-19 based on network pharmacology and molecular docking method. Chin Tradit Herbal Drugs 2020; 51(04): 836-44.
[51]
Yang L, Zhao Y, Qu R, Fu Y, Zhou C, Yu J. A network pharmacology and molecular docking approach to reveal the mechanism of Chaihu Anxin capsule in depression. Front Endocrinol (Lausanne) 2023; 14: 1256045.
[http://dx.doi.org/10.3389/fendo.2023.1256045] [PMID: 37745719]
[52]
Amiran MR, Taghdir M, Abasi Joozdani F. Molecular insights into the behavior of the allosteric and ATP-competitive inhibitors in interaction with AKT1 protein: A molecular dynamics study. Int J Biol Macromol 2023; 242(Pt 2): 124853.
[http://dx.doi.org/10.1016/j.ijbiomac.2023.124853] [PMID: 37172698]
[53]
Sun T, Quan W, Peng S, et al. Network pharmacology-based strategy combined with molecular docking and in validation study to explore the underlying mechanism of Huo Luo Xiao Ling Dan in treating atherosclerosis. Drug Des Devel Ther 2022; 16: 1621-45.
[http://dx.doi.org/10.2147/DDDT.S357483] [PMID: 35669282]
[54]
Hu Q, Noor M, Wong YF, et al. In vitro anti-fibrotic activities of herbal compounds and herbs. Nephrol Dial Transplant 2009; 24(10): 3033-41.
[http://dx.doi.org/10.1093/ndt/gfp245] [PMID: 19474275]
[55]
Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol 2014; 60(5): 1090-6.
[http://dx.doi.org/10.1016/j.jhep.2013.12.025] [PMID: 24412603]
[56]
Wu H, Chen G, Wang J, Deng M, Yuan F, Gong J. TIM-4 interference in Kupffer cells against CCL4-induced liver fibrosis by mediating Akt1/Mitophagy signalling pathway. Cell Prolif 2020; 53(1): e12731.
[http://dx.doi.org/10.1111/cpr.12731] [PMID: 31755616]
[57]
Choudhury A, Bullock D, Lim A, et al. Inhibition of HSP90 and activation of HSF1 diminish macrophage NLRP3 inflammasome activity in alcohol-associated liver injury. Alcohol Clin Exp Res 2020; 44(6): 1300-11.
[http://dx.doi.org/10.1111/acer.14338] [PMID: 32282939]
[58]
Scheving LA, Zhang X, Threadgill DW, Russell WE. Hepatocyte ERBB3 and EGFR are required for maximal CCL4-induced liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2016; 311(5): G807-16.
[http://dx.doi.org/10.1152/ajpgi.00423.2015] [PMID: 27586651]
[59]
Deng YR, Ma HD, Tsuneyama K, et al. STAT3-mediated attenuation of CCL4-induced mouse liver fibrosis by the protein kinase inhibitor sorafenib. J Autoimmun 2013; 46: 25-34.
[http://dx.doi.org/10.1016/j.jaut.2013.07.008] [PMID: 23948302]
[60]
Asadipooya K, Lankarani KB, Raj R, Kalantarhormozi M. RAGE is a potential cause of onset and progression of nonalcoholic fatty liver disease. Int J Endocrinol 2019; 2019: 1-11.
[http://dx.doi.org/10.1155/2019/2151302] [PMID: 31641351]
[61]
Xiu AY, Ding Q, Li Z, Zhang CQ. Doxazosin attenuates liver fibrosis by inhibiting autophagy in hepatic stellate cells via activation of the PI3K/Akt/mTOR signaling pathway. Drug Des Devel Ther 2021; 15: 3643-59.
[http://dx.doi.org/10.2147/DDDT.S317701] [PMID: 34456560]
[62]
Dai C, Li H, Wang Y, Tang S, Velkov T, Shen J. Inhibition of oxidative stress and ALOX12 and NF-κB Pathways contribute to the protective effect of baicalein on carbon tetrachloride-induced acute liver injury. Antioxidants 2021; 10(6): 976.
[http://dx.doi.org/10.3390/antiox10060976] [PMID: 34207230]
[63]
Xiao T, Cui Y, Ji H, Yan L, Pei D, Qu S. Baicalein attenuates acute liver injury by blocking NLRP3 inflammasome. Biochem Biophys Res Commun 2021; 534: 212-8.
[http://dx.doi.org/10.1016/j.bbrc.2020.11.109] [PMID: 33272570]
[64]
Chen Y, Zhao Z, Li Y, et al. Baicalein alleviates hyperuricemia by promoting uric acid excretion and inhibiting xanthine oxidase. Phytomedicine 2021; 80: 153374.
[http://dx.doi.org/10.1016/j.phymed.2020.153374] [PMID: 33075645]
[65]
Dong Y, Xing Y, Sun J, Sun W, Xu Y, Quan C. Baicalein alleviates liver oxidative stress and apoptosis induced by high-level glucose through the activation of the PERK/Nrf2 signaling pathway. Molecules 2020; 25(3): 599.
[http://dx.doi.org/10.3390/molecules25030599] [PMID: 32019168]
[66]
Guo C, Li Q, Chen R, et al. Baicalein alleviates non-alcoholic fatty liver disease in mice by ameliorating intestinal barrier dysfunction. Food Funct 2023; 14(4): 2138-48.
[http://dx.doi.org/10.1039/D2FO03015B] [PMID: 36752061]
[67]
Ke M, Zhang Z, Xu B, et al. Baicalein and baicalin promote antitumor immunity by suppressing PD-L1 expression in hepatocellular carcinoma cells. Int Immunopharmacol 2019; 75: 105824.
[http://dx.doi.org/10.1016/j.intimp.2019.105824] [PMID: 31437792]
[68]
Lai CC, Huang PH, Yang AH, et al. Baicalein reduces liver injury induced by myocardial ischemia and reperfusion. Am J Chin Med 2016; 44(3): 531-50.
[http://dx.doi.org/10.1142/S0192415X16500294] [PMID: 27109160]
[69]
Li Y, Yang D, Jia Y, et al. Research Note: Anti-inflammatory effects and antiviral activities of baicalein and chlorogenic acid against infectious bursal disease virus in embryonic eggs. Poult Sci 2021; 100(4): 100987.
[http://dx.doi.org/10.1016/j.psj.2021.01.010] [PMID: 33639350]
[70]
Liu J, Zhang W, Li X, Xu S. New Insights into Baicalein’s effect on chlorpyrifos-induced liver injury in Carp: Involving macrophage polarization and pyroptosis. J Agric Food Chem 2023; 71(9): 4132-43.
[http://dx.doi.org/10.1021/acs.jafc.2c08580] [PMID: 36848483]
[71]
Shi L, Hao Z, Zhang S, et al. Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC. Biochem Pharmacol 2018; 150: 9-23.
[http://dx.doi.org/10.1016/j.bcp.2018.01.026] [PMID: 29338970]
[72]
Wu R, Murali R, Kabe Y, et al. Baicalein targets GTPase-mediated autophagy to eliminate liver tumor-initiating stem cell-like cells resistant to mtorc1 inhibition. Hepatology 2018; 68(5): 1726-40.
[http://dx.doi.org/10.1002/hep.30071] [PMID: 29729190]
[73]
Xing Y, Ren X, Li X, et al. Baicalein Enhances the effect of acarbose on the improvement of nonalcoholic fatty liver disease associated with prediabetes via the inhibition of de novo lipogenesis. J Agric Food Chem 2021; 69(34): 9822-36.
[http://dx.doi.org/10.1021/acs.jafc.1c04194] [PMID: 34406004]
[74]
Dai J, Liang K, Zhao S, et al. Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis. Proc Natl Acad Sci USA 2018; 115(26): E5896-905.
[http://dx.doi.org/10.1073/pnas.1801745115] [PMID: 29891721]
[75]
Jiang H, Yao Q, An Y, Fan L, Wang J, Li H. Baicalin suppresses the progression of Type 2 diabetes-induced liver tumor through regulating METTL3/m6A/HKDC1 axis and downstream p-JAK2/STAT1/clevaged Capase3 pathway. Phytomedicine 2022; 94: 153823.
[http://dx.doi.org/10.1016/j.phymed.2021.153823] [PMID: 34763315]
[76]
Liu WJ, Chen WW, Chen JY, et al. Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice. Phytother Res 2023; ptr.8010.
[http://dx.doi.org/10.1002/ptr.8010] [PMID: 37697721]
[77]
Sun J, Yang X, Sun H, et al. Baicalin inhibits Hepatocellular Carcinoma cell growth and metastasis by suppressing ROCK1 signaling. Phytother Res 2023; 37(9): 4117-32.
[http://dx.doi.org/10.1002/ptr.7873] [PMID: 37246830]
[78]
Wang Y, Jia Y, Yang X, Liang B, Gao H, Yang T. A potential role of Baicalin to inhibit apoptosis and protect against acute liver and kidney injury in rat preeclampsia model. Biomed Pharmacother 2018; 108: 1546-52.
[http://dx.doi.org/10.1016/j.biopha.2018.09.107] [PMID: 30372856]
[79]
Xu J, Li S, Jiang L, et al. Baicalin protects against zearalenone-induced chicks liver and kidney injury by inhibiting expression of oxidative stress, inflammatory cytokines and caspase signaling pathway. Int Immunopharmacol 2021; 100: 108097.
[http://dx.doi.org/10.1016/j.intimp.2021.108097] [PMID: 34521024]
[80]
Zhao S, Huang M, Yan L, et al. Exosomes derived from baicalin-pretreated mesenchymal stem cells alleviate hepatocyte ferroptosis after acute liver injury via the Keap1-NRF2 pathway. Oxid Med Cell Longev 2022; 2022: 1-18.
[http://dx.doi.org/10.1155/2022/8287227] [PMID: 35910831]
[81]
Lu L, Guo Q, Zhao L. Overview of oroxylin A: A promising flavonoid compound. Phytother Res 2016; 30(11): 1765-74.
[http://dx.doi.org/10.1002/ptr.5694] [PMID: 27539056]
[82]
Zhao Y, Zhu Q, Bu X, et al. Triggering apoptosis by oroxylin A through caspase-8 activation and p62/SQSTM1 proteolysis. Redox Biol 2020; 29: 101392.
[http://dx.doi.org/10.1016/j.redox.2019.101392] [PMID: 31926620]
[83]
Yao J, Wang J, Xu Y, et al. CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regulating the SIRT1- FOXO3-BNIP3 axis and enhances the therapeutic effects involving mitochondrial dysfunction in hepatocellular carcinoma. Autophagy 2022; 18(8): 1879-97.
[http://dx.doi.org/10.1080/15548627.2021.2007027] [PMID: 34890308]
[84]
Wang F, Jia Y, Li M, et al. Blockade of glycolysis-dependent contraction by oroxylin a via inhibition of lactate dehydrogenase-a in hepatic stellate cells. Cell Commun Signal 2019; 17(1): 11.
[http://dx.doi.org/10.1186/s12964-019-0324-8] [PMID: 30744642]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy