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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

Bioactive Phytochemicals and Molecular Mechanisms of Artemisiae capillariae against Drug Induced Liver Injury based on Network Pharmacology

Author(s): Wen Shan, Zhiping Yang, Yan Zhao, Yan Hu, Ran Yan, Xi Wu, Junzi Huang* and Musen Lin*

Volume 19, Issue 6, 2023

Published on: 09 March, 2023

Page: [476 - 489] Pages: 14

DOI: 10.2174/1573409919666230301092720

Price: $65

Abstract

Background: Artemisiae capillariae (Yinchen, YC) is a well-known herbal medicine used to treat drug-induced liver diseases, while the bioactive phytochemicals and pharmacological targets of YC remain unclear.

Objective: The study aimed to probe the key active components in YC and determine the potential molecular mechanisms of YC protect against DILI.

Methods: In this study, we first delved into the active chemicals and targets of YC, identified potential anti-AILI targets for YC, mapped the components-targets network, performed proteinprotein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analyses of the action targets. This led to figure out the liver protective mechanism of YC against AILI. Analyzing the molecular docking of key targets, binding domain of ingredients and targets reveals the effective interaction, and the binding energy explains the efficiency and stability of the interactions.

Results: Network analysis identified 53 components in YC; by systematic screening 13 compounds were selected, which were associated with 123 AILI-related genes. The core ingredients were quercetin, capillarisin and Skrofulein, and the identified crucial genes were AKT1, TNF, and IL6. The GO and KEGG pathway enrichment analysis results indicated that the anti-AILI targets of YC mainly take a part in the regulation of oxidative stress and immune, with related signaling pathways including PI3K/AKT and IL17. Furthermore, the binding pockets of YC bioactive ingredients and key targets were revealed, and the binding ability was proved by molecular docking analysis.

Conclusion: This study has revealed the potential bioactive molecules and mechanism of YC in AILI and provided a possible strategy for the identification of active phytochemicals against druginduced liver injury.

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[1]
Li, X.; Tang, J.; Mao, Y. Incidence and risk factors of drug‐induced liver injury. Liver Int., 2022, 42(9), 1999-2014.
[http://dx.doi.org/10.1111/liv.15262] [PMID: 35353431]
[2]
Segovia-Zafra, A.; Di Zeo-Sánchez, D.E.; López-Gómez, C.; Pérez-Valdés, Z.; García-Fuentes, E.; Andrade, R.J.; Lucena, M.I.; Villanueva-Paz, M. Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction. Acta Pharm. Sin. B, 2021, 11(12), 3685-3726.
[http://dx.doi.org/10.1016/j.apsb.2021.11.013] [PMID: 35024301]
[3]
Borlak, J.; Chatterji, B.; Londhe, K.B.; Watkins, P.B. Serum acute phase reactants hallmark healthy individuals at risk for acetaminophen-induced liver injury. Genome Med., 2013, 5(9), 86.
[http://dx.doi.org/10.1186/gm493] [PMID: 24070255]
[4]
Yan, X.; Sun, Y.; Ren, S.; Zhao, L.; Liu, W.; Chen, C.; Wang, Z.; Li, W. Dietary α-mangostin provides protective effects against acetaminophen-induced hepatotoxicity in mice via Akt/mTOR-mediated inhibition of autophagy and apoptosis. Int. J. Mol. Sci., 2018, 19(5), 1335.
[http://dx.doi.org/10.3390/ijms19051335] [PMID: 29723988]
[5]
Wang, J.; Shi, Q.; Zhou, Q.; Zhang, L.; Qiu, Y.; Lou, D.; Zhou, L.; Yang, B.; He, Q.; Weng, Q.; Wang, J. Sapidolide A alleviates acetaminophen-induced acute liver injury by inhibiting NLRP3 inflammasome activation in macrophages. Acta Pharmacol. Sin., 2022, 43(8), 2016-2025.
[http://dx.doi.org/10.1038/s41401-021-00842-x] [PMID: 35022542]
[6]
Abbas, A.A.; Hamdy, A.; Ahmed, A.E. Compromised blood–bile barrier after acetaminophen overdose. Arch. Toxicol., 2022, 96(10), 2825-2827.
[http://dx.doi.org/10.1007/s00204-022-03335-w] [PMID: 35849165]
[7]
Chang, L.; Xu, D.; Zhu, J.; Ge, G.; Kong, X.; Zhou, Y. Herbal therapy for the treatment of acetaminophen-associated liver injury: Recent advances and future perspectives. Front. Pharmacol., 2020, 11, 313.
[http://dx.doi.org/10.3389/fphar.2020.00313] [PMID: 32218738]
[8]
Subramanya, S.; Venkataraman, B.; Meeran, M.; Goyal, S.; Patil, C.; Ojha, S. Therapeutic potential of plants and plant derived phytochemicals against acetaminophen-induced liver injury. Int. J. Mol. Sci., 2018, 19(12), 3776.
[http://dx.doi.org/10.3390/ijms19123776] [PMID: 30486484]
[9]
Su, H.; Wang, Q.; Li, Y.; Jin, J.; Tan, B.; Yan, D.; Zou, B.; Song, G.; Weng, F.; Qiu, F. Effect of different ratios of Yinchen and Gancao decoction on anti-treated cholestatic liver injury in mice and its potential underlying mechanism. Front. Pharmacol., 2021, 12, 611610.
[http://dx.doi.org/10.3389/fphar.2021.611610] [PMID: 33935705]
[10]
Jiang, H.; Mao, T.; Liu, Y.; Tan, X.; Sun, Z.; Cheng, Y.; Han, X.; Zhang, Y.; Wang, J.; Shi, L.; Guo, Y.; Li, J.; Han, H. Protective effects and mechanisms of Yinchen Linggui Zhugan decoction in HFD-induced nonalcoholic fatty liver disease rats based on network pharmacology and experimental verification. Front. Pharmacol., 2022, 13, 908128.
[http://dx.doi.org/10.3389/fphar.2022.908128] [PMID: 35721171]
[11]
Douillet, D.; Chapelle, C.; Ollier, E.; Mismetti, P.; Roy, P.M.; Laporte, S. Prevention of venous thromboembolic events in patients with lower leg immobilization after trauma: Systematic review and network meta-analysis with meta-epsidemiological approach. PLoS Med., 2022, 19(7), e1004059.
[http://dx.doi.org/10.1371/journal.pmed.1004059] [PMID: 35849624]
[12]
Nam, H.H.; Kim, J.S.; Lee, J.; Seo, Y.H.; Kim, H.S.; Ryu, S.M.; Choi, G.; Moon, B.C.; Lee, A.Y. Pharmacological effects of Agastache rugosa against gastritis using a network pharmacology approach. Biomolecules, 2020, 10(9), 1298.
[http://dx.doi.org/10.3390/biom10091298] [PMID: 32916904]
[13]
Bai, L.L.; Chen, H.; Zhou, P.; Yu, J. Identification of tumor necrosis factor-alpha (TNF-α) inhibitor in rheumatoid arthritis using network pharmacology and molecular docking. Front. Pharmacol., 2021, 12, 690118.
[http://dx.doi.org/10.3389/fphar.2021.690118] [PMID: 34093213]
[14]
Jo, H.; Mondal, S.; Tan, D.; Nagata, E.; Takizawa, S.; Sharma, A.K.; Hou, Q.; Shanmugasundaram, K.; Prasad, A.; Tung, J.K.; Tejeda, A.O.; Man, H.; Rigby, A.C.; Luo, H.R. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc. Natl. Acad. Sci. USA, 2012, 109(26), 10581-10586.
[http://dx.doi.org/10.1073/pnas.1202810109] [PMID: 22689977]
[15]
Ghandadi, M.; Sahebkar, A. Curcumin: An effective inhibitor of interleukin-6. Curr. Pharm. Des., 2017, 23(6), 921-931.
[http://dx.doi.org/10.2174/1381612822666161006151605] [PMID: 27719643]
[16]
Sivilotti, M.L.A.; Yarema, M.C.; Juurlink, D.N. Treating acetaminophen overdose. CMAJ, 2022, 194(15), E554.
[http://dx.doi.org/10.1503/cmaj.210703] [PMID: 35440504]
[17]
Li, X.; Tang, Q.; Meng, F.; Du, P.; Chen, W. INPUT: An intelligent network pharmacology platform unique for traditional Chinese medicine. Comput. Struct. Biotechnol. J., 2022, 20, 1345-1351.
[http://dx.doi.org/10.1016/j.csbj.2022.03.006] [PMID: 35356545]
[18]
Zhou, W.; Yang, K.; Zeng, J.; Lai, X.; Wang, X.; Ji, C.; Li, Y.; Zhang, P.; Li, S. FordNet: Recommending traditional Chinese medicine formula via deep neural network integrating phenotype and molecule. Pharmacol. Res., 2021, 173, 105752.
[http://dx.doi.org/10.1016/j.phrs.2021.105752] [PMID: 34481072]
[19]
Ahmed, O.M.; Elkomy, M.H.; Fahim, H.I.; Ashour, M.B.; Naguib, I.A.; Alghamdi, B.S.; Mahmoud, H.U.R.; Ahmed, N.A. Rutin and Quercetin counter doxorubicin-induced liver toxicity in wistar rats via their modulatory effects on inflammation, oxidative stress, apoptosis, and Nrf2. Oxid. Med. Cell. Longev., 2022, 2022, 1-19.
[http://dx.doi.org/10.1155/2022/2710607] [PMID: 35936216]
[20]
Wei, X.; Yang, D.; Xing, Z.; Zhao, C.; Wang, L.; Fan, Y.; Nie, H.; Liu, H. Quercetin loaded liposomes modified with galactosylated chitosan prevent LPS/D-GalN induced acute liver injury. Mater. Sci. Eng. C, 2021, 131, 112527.
[http://dx.doi.org/10.1016/j.msec.2021.112527] [PMID: 34857306]
[21]
Abdelhalim, M.; Moussa, S.; Qaid, H.; Al-Ayed, M. Potential effects of different natural antioxidants on inflammatory damage and oxidative-mediated hepatotoxicity induced by gold nanoparticles. Int. J. Nanomedicine, 2018, 13, 7931-7938.
[http://dx.doi.org/10.2147/IJN.S171931] [PMID: 30538469]
[22]
Yu, Z.; Tang, L.; Chen, L.; Li, J.; Wu, W.; Hu, C. Capillarisin suppresses lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells by suppressing TLR4-mediated NF-κB and MAPKs signaling pathway. Neurochem. Res., 2015, 40(6), 1095-1101.
[http://dx.doi.org/10.1007/s11064-015-1567-4] [PMID: 25894679]
[23]
Che, D.N.; Shin, J.Y.; Kang, H.J.; Cho, B.O.; Park, J.H.; Wang, F.; Hao, S.; Sim, J.S.; Sim, D.J.; Jang, S.I. Ameliorative effects of Cirsium japonicum extract and main component cirsimaritin in mice model of high‐fat diet‐induced metabolic dysfunction‐associated fatty liver disease. Food Sci. Nutr., 2021, 9(11), 6060-6068.
[http://dx.doi.org/10.1002/fsn3.2548] [PMID: 34760237]
[24]
Yan, M.; Huo, Y.; Yin, S.; Hu, H. Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions. Redox Biol., 2018, 17, 274-283.
[http://dx.doi.org/10.1016/j.redox.2018.04.019] [PMID: 29753208]
[25]
Nam, E.J.; Hayashida, K.; Aquino, R.S.; Couchman, J.R.; Kozar, R.A.; Liu, J.; Park, P.W. Syndecan‐1 limits the progression of liver injury and promotes liver repair in acetaminophen‐induced liver injury in mice. Hepatology, 2017, 66(5), 1601-1615.
[http://dx.doi.org/10.1002/hep.29265] [PMID: 28543100]
[26]
Wang, J.; Zhang, L.; Shi, Q.; Yang, B.; He, Q.; Wang, J.; Weng, Q. Targeting innate immune responses to attenuate acetaminophen-induced hepatotoxicity. Biochem. Pharmacol., 2022, 202, 115142.
[http://dx.doi.org/10.1016/j.bcp.2022.115142] [PMID: 35700755]
[27]
Krenkel, O.; Mossanen, J.C.; Tacke, F. Immune mechanisms in acetaminophen-induced acute liver failure. Hepatobiliary Surg. Nutr., 2014, 3(6), 331-343.
[PMID: 25568858]
[28]
Hou, X.; Liu, Q.; Gao, Y.; Yong, L.; Xie, H.; Li, W.; Zhou, Y.; Liu, J.; Feng, L.; Xu, L.; Shen, Y.; Wang, H. Mesencephalic astrocyte-derived neurotrophic factor reprograms macrophages to ameliorate acetaminophen-induced acute liver injury via p38 MAPK pathway. Cell Death Dis., 2022, 13(2), 100.
[http://dx.doi.org/10.1038/s41419-022-04555-9] [PMID: 35110525]
[29]
Noda, T.; Kato, R.; Hattori, T.; Furukawa, Y.; Ijiri, Y.; Tanaka, K. Role of caspase-8 and/or -9 as biomarkers that can distinguish the potential to cause toxic and immune related-adverse event, for the progress of acetaminophen-induced liver injury. Life Sci., 2022, 294, 120351.
[http://dx.doi.org/10.1016/j.lfs.2022.120351] [PMID: 35092733]
[30]
Konieczny, P.; Xing, Y.; Sidhu, I.; Subudhi, I.; Mansfield, K.P.; Hsieh, B.; Biancur, D.E.; Larsen, S.B.; Cammer, M.; Li, D.; Landén, N.X.; Loomis, C.; Heguy, A.; Tikhonova, A.N.; Tsirigos, A.; Naik, S. Interleukin-17 governs hypoxic adaptation of injured epithelium. Science, 2022, 377(6602), eabg9302.
[http://dx.doi.org/10.1126/science.abg9302] [PMID: 35709248]
[31]
Xing, H.; Fu, R.; Cheng, C.; Cai, Y.; Wang, X.; Deng, D.; Gong, X.; Chen, J. Hyperoside protected against oxidative stress-induced liver injury via the PHLPP2-AKT-GSK-3β signaling pathway in vivo and in vitro. Front. Pharmacol., 2020, 11, 1065.
[http://dx.doi.org/10.3389/fphar.2020.01065] [PMID: 32765271]
[32]
An, J.; He, H.; Yao, W.; Shang, Y.; Jiang, Y.; Yu, Z. PI3K/Akt/FoxO pathway mediates glycolytic metabolism in HepG2 cells exposed to triclosan (TCS). Environ. Int., 2020, 136, 105428.
[http://dx.doi.org/10.1016/j.envint.2019.105428] [PMID: 31918333]
[33]
Weiss, T.S.; Lupke, M.; Dayoub, R.; Geissler, E.K.; Schlitt, H.J.; Melter, M.; Eggenhofer, E. Augmenter of liver regeneration reduces ischemia reperfusion injury by less chemokine expression, Gr-1 infiltration and oxidative stress. Cells, 2019, 8(11), 1421.
[http://dx.doi.org/10.3390/cells8111421] [PMID: 31718093]
[34]
He, S.; Cui, S.; Song, W.; Jiang, Y.; Chen, H.; Liao, D.; Lu, X.; Li, J.; Chen, X.; Peng, L. Interleukin-17 weakens the NAFLD/NASH process by facilitating intestinal barrier restoration depending on the gut microbiota. MBio, 2022, 13(2), e03688-e21.
[http://dx.doi.org/10.1128/mbio.03688-21] [PMID: 35266816]

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