Decoding the mechanism of Qingjie formula in the prevention of COVID-19 based on network pharmacology and molecular docking
Yu Pan, Wanchun Lin, Yueyue Huang, Jingye Pan, Yihua Dong
Heliyon, doi:10.1016/j.heliyon.2024.e39167
Traditional Chinese medicine (TCM) has played a positive role in preventing and controlling the coronavirus disease 2019 (COVID-19) epidemic. Qingjie formula (QJF) developed to prevent COVID-19 is widely used in Wenzhou, Zhejiang province, China. However, the biological active ingredients of QJF and their specific mechanisms for preventing COVID-19 remain unclear. The study focused on exploring the pharmacological mechanism of QJF for the prevention of COVID-19 based on network pharmacology and molecular docking. The active ingredients of QJF were screened by TCMSP database. Databases such as Genecards and Swiss Target Prediction predicted potential targets of QJF against COVID-19. The "drug-active ingredient-potential target" network was constructed by Cytoscape software. We used STRING database to construct the proteinprotein interaction (PPI) network. Enrichment of biological functions and signaling pathways were analyzed by using the DAVID database and R language. Then AutoDock Vina and Python software were used for molecular docking of hub targets and active ingredients. 147 active ingredients interacted with 316 potential targets of COVID-19. A PPI network consisting of 30 hub genes was constructed, and the top 10 hub genes were ALB, AKT1, TP53, TNF, IL6, VEGFA, IL1B, CASP3, JUN and STAT3. The results of GO analysis showed that these targets were mainly enriched in cell responses to oxidative stress, chemical stress, and other functions. KEGG analysis revealed that viral protein interactions with cytokines (e.g., human cytomegalovirus infection), endocrine resistance pathways (e.g., AGE-RAGE signaling pathway), PI3K-Akt signaling pathway, and lipid and atherosclerosis signaling pathway were the major signaling pathways. Moreover, the core active ingredients of QJF had good binding affinity with hub genes by molecular docking. QJF plays an important role in the prevention of COVID-19 by regulating host immune inflammatory response and oxidative stress response, inhibiting virus, improving immune function, regulating the hypoxia-cytokine storm, and inhibiting cell migration.
Introduction Coronavirus disease 2019 (COVID-19) was first discovered in Wuhan, China, and is a highly contagious disease caused by severe
Ethics statement Not applicable.
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Abbreviation
References
Araf, Akter, Tang, Fatemi, Parvez et al., Omicron variant of SARS-cov-2: genomics, transmissibility, and responses to current covid-19 vaccines, J. Med. Virol,
doi:10.1002/jmv.27588Chen, Zhang, Wang, Ye, Huang, Differential ability of formononetin to stimulate proliferation of endothelial cells and breast cancer cells via a feedback loop involving MicroRNA-375, RASD1, and ERα, Mol. Carcinog,
doi:10.1002/mc.22531Chowdhury, In silico investigation of phytoconstituents from indian medicinal herb 'tinospora cordifolia (giloy)' against SARS-cov-2 (covid-19) by molecular dynamics approach, J. Biomol. Struct. Dyn,
doi:10.1080/07391102.2020.1803968Colunga, Berrill, Catravas, Marik, Quercetin and vitamin c: an experimental, synergistic therapy for the prevention and treatment of SARS-cov-2 related disease (covid-19), Front. Immunol,
doi:10.3389/fimmu.2020.01451Devaraj, Roy, Royapuram, Magesh, Varikalam et al., Beta-sitosterol attenuates carbon tetrachloride-induced oxidative stress and chronic liver injury in rats, Naunyn-Schmiedeberg's, Arch. Pharmacol,
doi:10.1007/s00210-020-01810-8Feng, Ao, Yue, Peng, Systems pharmacology reveals the unique mechanism features of shenzhu capsule for treatment of ulcerative colitis in comparison with synthetic drugs, Sci. Rep,
doi:10.1038/s41598-018-34509-1Gansukh, Nile, Kim, Oh, Nile, New insights into antiviral and cytotoxic potential of quercetin and its derivatives -a biochemical perspective, Food Chem,
doi:10.1016/j.foodchem.2020.127508Huang, Zhang, Huang, Huang, Huang et al., A network pharmacology strategy to investigate the anti-inflammatory mechanism of luteolin combined with in vitro transcriptomics and proteomics, Int. Immunopharm,
doi:10.1016/j.intimp.2020.106727Lai, Han, Lao, Li, Xiao et al., Phillyrin for covid-19 and influenza co-infection: a potential therapeutic strategy targeting host based on bioinformatics analysis, Front. Pharmacol,
doi:10.3389/fphar.2021.754241Li, Du, Liu, Liu, Zhi et al., A systems pharmacology approach for identifying the multiple mechanisms of action for the rougui-fuzi herb pair in the treatment of cardiocerebral vascular diseases, Evid.-Based Complement Altern. Med,
doi:10.1155/2020/5196302Li, Fan, Jia, Lu, Zhang, Network pharmacology in traditional Chinese medicine, Evid. Based Complement. Alternat. Med,
doi:10.1155/2014/138460Li, Yu, Zhang, Ren, Peluffo et al., Network bioinformatics analysis provides insight into drug repurposing for covid-19, Med Drug Discov,
doi:10.1016/j.medidd.2021.100090Lipsitch, Swerdlow, Finelli, Defining the epidemiology of covid-19 studies needed, N. Engl. J. Med,
doi:10.1056/NEJMp2002125Liu, Cooley, Jarnicki, Borghuis, Nair et al., Fibulin-1c regulates transforming growth factor-beta activation in pulmonary tissue fibrosis, Jci Insight,
doi:10.1172/jci.insight.124529Liu, Gao, Yuan, Yang, Shi et al., Efficacy and safety of integrated traditional Chinese and western medicine for corona virus disease 2019 (covid-19): a systematic review and meta-analysis, Pharmacol. Res,
doi:10.1016/j.phrs.2020.104896Malviya, Fuloria, Verma, Subramaniyan, Sathasivam et al., Commercial utilities and future perspective of nanomedicines, PeerJ,
doi:10.7717/peerj.12392Misawa, Tanaka, Nomaguchi, Nabeshima, Yamada et al., Oral ingestion of aloe vera phytosterols alters hepatic gene expression profiles and ameliorates obesity-associated metabolic disorders in zucker diabetic fatty rats, J. Agric. Food Chem,
doi:10.1021/jf204465jMotallebi, Bhia, Rajani, Bhia, Tabarraei et al., Naringenin: a potential flavonoid phytochemical for cancer therapy, Life Sci,
doi:10.1016/j.lfs.2022.120752Mou, Zhou, Zhou, Liu, Chen et al., A bioinformatics and network pharmacology approach to the mechanisms of action of shenxiao decoction for the treatment of diabetic nephropathy, Phytomedicine,
doi:10.1016/j.phymed.2020.153192Nishikawa, Shimoda, Fereig, Moritaka, Umeda et al., Neospora caninum dense granule protein 7 regulates the pathogenesis of neosporosis by modulating host immune response, Appl. Environ. Microbiol,
doi:10.1128/AEM.01350-18Pan, None, Heliyon
Ren, Lu, Qian, Chen, Wu et al., Recent progress regarding kaempferol for the treatment of various diseases, Exp. Ther. Med,
doi:10.3892/etm.2019.7886Sathasivam, Haris, Fuloria, Fuloria, Malviya et al., Chemical modification of banana trunk fibers for the production of green composites, Polymers,
doi:10.3390/polym13121943Schultheiss, Willscher, Paschold, Gottschick, Klee et al., The il-1beta, il-6, and tnf cytokine triad is associated with post-acute sequelae of covid-19, Cell Rep. Med,
doi:10.1016/j.xcrm.2022.100663Sharmila, Sindhu, Modulation of angiogenesis, proliferative response and apoptosis by beta-sitosterol in rat model of renal carcinogenesis, Indian J. Clin. Biochem,
doi:10.1007/s12291-016-0583-8Shen, Kong, Qiu, Yang, Wang et al., Identification of core genes and outcomes in hepatocellular carcinoma by bioinformatics analysis, J. Cell. Biochem,
doi:10.1002/jcb.28290Song, Zhao, Li, Su, Jiang et al., Interpretation of the traditional Chinese medicine portion of the diagnosis and treatment protocol for corona virus disease 2019 (trial version 7), J. Tradit. Chin. Med,
doi:10.19852/j.cnki.jtcm.2020.03.019Van Der Lugt, Weseler, Vrolijk, Opperhuizen, Bast, Dietary advanced glycation endproducts decrease glucocorticoid sensitivity in vitro, Nutrients,
doi:10.3390/nu12020441Xu, Han, Li, Sun, Wang et al., Effective treatment of severe covid-19 patients with tocilizumab, Proc. Natl. Acad. Sci. U. S. A,
doi:10.1073/pnas.2005615117Xu, Xu, Jiang, Dua, Hansbro et al., SARS-cov-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis, Respir. Res,
doi:10.1186/s12931-020-01445-6Xue, Li, Lu, Li, Crosstalk between circrnas and the pi3k/akt signaling pathway in cancer progression, Signal Transduct. Targeted Ther,
doi:10.1038/s41392-021-00788-wYang, Li, Lv, Qian, Chen et al., Study on the multitarget mechanism and key active ingredients of herba siegesbeckiae and volatile oil against rheumatoid arthritis based on network pharmacology, Evid. Based Complement. Alternat. Med,
doi:10.1155/2019/8957245Young, Ong, Ng, Anderson, Chia et al., Viral dynamics and immune correlates of coronavirus disease 2019 (covid-19) severity, Clin. Infect. Dis,
doi:10.1093/cid/ciaa1280Zhang, Zhao, Zhang, Wang, Li et al., The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (covid-19): the perspectives of clinical immunologists from China, Clin, Immunol,
doi:10.1016/j.clim.2020.108393Zhao, Lv, Wu, Zeng, Guo et al., Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of deng-zhan-xi-xin injection in the treatment of ischemic stroke, Pharmacol. Res,
doi:10.1016/j.phrs.2019.104365Zhao, Tian, Lu, Yang, Zeng et al., Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of qing-fei-pai-du decoction in the treatment of covid-19, Phytomedicine,
doi:10.1016/j.phymed.2020.153315{ 'indexed': { 'date-parts': [[2024, 10, 14]],
'date-time': '2024-10-14T03:10:24Z',
'timestamp': 1728875424186},
'reference-count': 44,
'publisher': 'Elsevier BV',
'issue': '20',
'license': [ { 'start': { 'date-parts': [[2024, 10, 1]],
'date-time': '2024-10-01T00:00:00Z',
'timestamp': 1727740800000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'},
{ 'start': { 'date-parts': [[2024, 10, 1]],
'date-time': '2024-10-01T00:00:00Z',
'timestamp': 1727740800000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/legal/tdmrep-license'},
{ 'start': { 'date-parts': [[2024, 10, 8]],
'date-time': '2024-10-08T00:00:00Z',
'timestamp': 1728345600000},
'content-version': 'vor',
'delay-in-days': 7,
'URL': 'http://creativecommons.org/licenses/by-nc-nd/4.0/'}],
'content-domain': { 'domain': ['cell.com', 'elsevier.com', 'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2024, 10]]},
'DOI': '10.1016/j.heliyon.2024.e39167',
'type': 'journal-article',
'created': { 'date-parts': [[2024, 10, 11]],
'date-time': '2024-10-11T23:16:33Z',
'timestamp': 1728688593000},
'page': 'e39167',
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Decoding the mechanism of Qingjie formula in the prevention of COVID-19 based on network '
'pharmacology and molecular docking',
'prefix': '10.1016',
'volume': '10',
'author': [ {'given': 'Yu', 'family': 'Pan', 'sequence': 'first', 'affiliation': []},
{'given': 'Wanchun', 'family': 'Lin', 'sequence': 'additional', 'affiliation': []},
{'given': 'Yueyue', 'family': 'Huang', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jingye', 'family': 'Pan', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-7828-4945',
'authenticated-orcid': False,
'given': 'Yihua',
'family': 'Dong',
'sequence': 'additional',
'affiliation': []}],
'member': '78',
'reference': [ { 'issue': '13',
'key': '10.1016/j.heliyon.2024.e39167_bib1',
'doi-asserted-by': 'crossref',
'first-page': '1194',
'DOI': '10.1056/NEJMp2002125',
'article-title': 'Defining the epidemiology of covid-19 studies needed',
'volume': '382',
'author': 'Lipsitch',
'year': '2020',
'journal-title': 'N. Engl. J. Med.'},
{ 'issue': '1',
'key': '10.1016/j.heliyon.2024.e39167_bib2',
'doi-asserted-by': 'crossref',
'first-page': '94',
'DOI': '10.1038/s41392-022-00950-y',
'article-title': 'Advances in covid-19 mrna vaccine development',
'volume': '7',
'author': 'Fang',
'year': '2022',
'journal-title': 'Signal Transduct. Targeted Ther.'},
{ 'issue': '5',
'key': '10.1016/j.heliyon.2024.e39167_bib3',
'doi-asserted-by': 'crossref',
'first-page': '1825',
'DOI': '10.1002/jmv.27588',
'article-title': 'Omicron variant of SARS-cov-2: genomics, transmissibility, and '
'responses to current covid-19 vaccines',
'volume': '94',
'author': 'Araf',
'year': '2022',
'journal-title': 'J. Med. Virol.'},
{ 'issue': '6',
'key': '10.1016/j.heliyon.2024.e39167_bib4',
'doi-asserted-by': 'crossref',
'first-page': '363',
'DOI': '10.1038/s41577-020-0311-8',
'article-title': 'The trinity of covid-19: immunity, inflammation and intervention',
'volume': '20',
'author': 'Tay',
'year': '2020',
'journal-title': 'Nat. Rev. Immunol.'},
{ 'issue': '10223',
'key': '10.1016/j.heliyon.2024.e39167_bib5',
'doi-asserted-by': 'crossref',
'first-page': '497',
'DOI': '10.1016/S0140-6736(20)30183-5',
'article-title': 'Clinical features of patients infected with 2019 novel coronavirus in '
'wuhan, China',
'volume': '395',
'author': 'Huang',
'year': '2020',
'journal-title': 'Lancet'},
{ 'issue': '22',
'key': '10.1016/j.heliyon.2024.e39167_bib6',
'doi-asserted-by': 'crossref',
'first-page': '1739',
'DOI': '10.1161/CIRCULATIONAHA.120.047419',
'article-title': 'Will complement inhibition be the new target in treating '
'covid-19-related systemic thrombosis?',
'volume': '141',
'author': 'Campbell',
'year': '2020',
'journal-title': 'Circulation'},
{ 'issue': '6489',
'key': '10.1016/j.heliyon.2024.e39167_bib7',
'doi-asserted-by': 'crossref',
'first-page': '356',
'DOI': '10.1126/science.368.6489.356',
'article-title': 'A rampage through the body',
'volume': '368',
'author': 'Wadman',
'year': '2020',
'journal-title': 'Science'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib8',
'article-title': 'The use of anti-inflammatory drugs in the treatment of people with '
'severe coronavirus disease 2019 (covid-19): the perspectives of '
'clinical immunologists from China, Clin',
'volume': '214',
'author': 'Zhang',
'year': '2020',
'journal-title': 'Immunol.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib9',
'doi-asserted-by': 'crossref',
'DOI': '10.7717/peerj.12392',
'article-title': 'Commercial utilities and future perspective of nanomedicines',
'volume': '9',
'author': 'Malviya',
'year': '2021',
'journal-title': 'PeerJ'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib10',
'article-title': 'Traditional Chinese medicine for covid-19 treatment',
'volume': '155',
'author': 'Ren',
'year': '2020',
'journal-title': 'Pharmacol. Res.'},
{ 'issue': '3',
'key': '10.1016/j.heliyon.2024.e39167_bib11',
'first-page': '497',
'article-title': 'Interpretation of the traditional Chinese medicine portion of the '
'diagnosis and treatment protocol for corona virus disease 2019 (trial '
'version 7)',
'volume': '40',
'author': 'Song',
'year': '2020',
'journal-title': 'J. Tradit. Chin. Med.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib12',
'article-title': 'Network pharmacology in traditional Chinese medicine',
'volume': '2014',
'author': 'Li',
'year': '2014',
'journal-title': 'Evid. Based Complement. Alternat. Med.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib13',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.phymed.2020.153192',
'article-title': 'A bioinformatics and network pharmacology approach to the mechanisms of '
'action of shenxiao decoction for the treatment of diabetic nephropathy',
'volume': '69',
'author': 'Mou',
'year': '2020',
'journal-title': 'Phytomedicine'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib14',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.phrs.2019.104365',
'article-title': 'Computational systems pharmacology reveals an antiplatelet and '
'neuroprotective mechanism of deng-zhan-xi-xin injection in the '
'treatment of ischemic stroke',
'volume': '147',
'author': 'Zhao',
'year': '2019',
'journal-title': 'Pharmacol. Res.'},
{ 'issue': '1',
'key': '10.1016/j.heliyon.2024.e39167_bib15',
'doi-asserted-by': 'crossref',
'DOI': '10.1038/s41598-018-34509-1',
'article-title': 'Systems pharmacology reveals the unique mechanism features of shenzhu '
'capsule for treatment of ulcerative colitis in comparison with '
'synthetic drugs',
'volume': '8',
'author': 'Feng',
'year': '2018',
'journal-title': 'Sci. Rep.'},
{ 'issue': '1',
'key': '10.1016/j.heliyon.2024.e39167_bib16',
'doi-asserted-by': 'crossref',
'first-page': '182',
'DOI': '10.1186/s12931-020-01445-6',
'article-title': 'SARS-cov-2 induces transcriptional signatures in human lung epithelial '
'cells that promote lung fibrosis',
'volume': '21',
'author': 'Xu',
'year': '2020',
'journal-title': 'Respir. Res.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib17',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.phymed.2020.153315',
'article-title': 'Systems pharmacological study illustrates the immune regulation, '
'anti-infection, anti-inflammation, and multi-organ protection mechanism '
'of qing-fei-pai-du decoction in the treatment of covid-19',
'volume': '85',
'author': 'Zhao',
'year': '2021',
'journal-title': 'Phytomedicine'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib18',
'article-title': 'Network bioinformatics analysis provides insight into drug repurposing '
'for covid-19',
'volume': '10',
'author': 'Li',
'year': '2021',
'journal-title': 'Med Drug Discov'},
{ 'issue': '2',
'key': '10.1016/j.heliyon.2024.e39167_bib19',
'doi-asserted-by': 'crossref',
'first-page': '623',
'DOI': '10.1021/acs.jproteome.8b00702',
'article-title': 'Cytoscape stringapp: network analysis and visualization of proteomics '
'data',
'volume': '18',
'author': 'Doncheva',
'year': '2019',
'journal-title': 'J. Proteome Res.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib20',
'doi-asserted-by': 'crossref',
'DOI': '10.1155/2019/8957245',
'article-title': 'Study on the multitarget mechanism and key active ingredients of herba '
'siegesbeckiae and volatile oil against rheumatoid arthritis based on '
'network pharmacology',
'volume': '2019',
'author': 'Yang',
'year': '2019',
'journal-title': 'Evid. Based Complement. Alternat. Med.'},
{ 'issue': '6',
'key': '10.1016/j.heliyon.2024.e39167_bib21',
'doi-asserted-by': 'crossref',
'first-page': '10069',
'DOI': '10.1002/jcb.28290',
'article-title': 'Identification of core genes and outcomes in hepatocellular carcinoma '
'by bioinformatics analysis',
'volume': '120',
'author': 'Shen',
'year': '2019',
'journal-title': 'J. Cell. Biochem.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib22',
'article-title': 'A systems pharmacology approach for identifying the multiple mechanisms '
'of action for the rougui-fuzi herb pair in the treatment of '
'cardiocerebral vascular diseases',
'volume': '2020',
'author': 'Li',
'year': '2020',
'journal-title': 'Evid.-Based Complement Altern. Med.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib23',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.phrs.2020.104896',
'article-title': 'Efficacy and safety of integrated traditional Chinese and western '
'medicine for corona virus disease 2019 (covid-19): a systematic review '
'and meta-analysis',
'volume': '158',
'author': 'Liu',
'year': '2020',
'journal-title': 'Pharmacol. Res.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib24',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.foodchem.2020.127508',
'article-title': 'New insights into antiviral and cytotoxic potential of quercetin and '
'its derivatives - a biochemical perspective',
'volume': '334',
'author': 'Gansukh',
'year': '2021',
'journal-title': 'Food Chem.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib25',
'doi-asserted-by': 'crossref',
'first-page': '1451',
'DOI': '10.3389/fimmu.2020.01451',
'article-title': 'Quercetin and vitamin c: an experimental, synergistic therapy for the '
'prevention and treatment of SARS-cov-2 related disease (covid-19)',
'volume': '11',
'author': 'Colunga',
'year': '2020',
'journal-title': 'Front. Immunol.'},
{ 'issue': '2',
'key': '10.1016/j.heliyon.2024.e39167_bib26',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/nu12020441',
'article-title': 'Dietary advanced glycation endproducts decrease glucocorticoid '
'sensitivity in vitro',
'volume': '12',
'author': 'van der Lugt',
'year': '2020',
'journal-title': 'Nutrients'},
{ 'issue': '17',
'key': '10.1016/j.heliyon.2024.e39167_bib27',
'doi-asserted-by': 'crossref',
'first-page': '6792',
'DOI': '10.1080/07391102.2020.1803968',
'article-title': 'In silico investigation of phytoconstituents from indian medicinal herb '
"'tinospora cordifolia (giloy)' against SARS-cov-2 (covid-19) by "
'molecular dynamics approach',
'volume': '39',
'author': 'Chowdhury',
'year': '2021',
'journal-title': 'J. Biomol. Struct. Dyn.'},
{ 'issue': '11',
'key': '10.1016/j.heliyon.2024.e39167_bib28',
'doi-asserted-by': 'crossref',
'first-page': '2799',
'DOI': '10.1021/jf204465j',
'article-title': 'Oral ingestion of aloe vera phytosterols alters hepatic gene expression '
'profiles and ameliorates obesity-associated metabolic disorders in '
'zucker diabetic fatty rats',
'volume': '60',
'author': 'Misawa',
'year': '2012',
'journal-title': 'J. Agric. Food Chem.'},
{ 'issue': '6',
'key': '10.1016/j.heliyon.2024.e39167_bib29',
'doi-asserted-by': 'crossref',
'first-page': '1067',
'DOI': '10.1007/s00210-020-01810-8',
'article-title': 'Beta-sitosterol attenuates carbon tetrachloride-induced oxidative '
'stress and chronic liver injury in rats',
'volume': '393',
'author': 'Devaraj',
'year': '2020',
'journal-title': 'Naunyn-Schmiedeberg’s Arch. Pharmacol.'},
{ 'issue': '2',
'key': '10.1016/j.heliyon.2024.e39167_bib30',
'doi-asserted-by': 'crossref',
'first-page': '142',
'DOI': '10.1007/s12291-016-0583-8',
'article-title': 'Modulation of angiogenesis, proliferative response and apoptosis by '
'beta-sitosterol in rat model of renal carcinogenesis',
'volume': '32',
'author': 'Sharmila',
'year': '2017',
'journal-title': 'Indian J. Clin. Biochem.'},
{ 'issue': '4',
'key': '10.1016/j.heliyon.2024.e39167_bib31',
'first-page': '2759',
'article-title': 'Recent progress regarding kaempferol for the treatment of various '
'diseases',
'volume': '18',
'author': 'Ren',
'year': '2019',
'journal-title': 'Exp. Ther. Med.'},
{ 'issue': '16',
'key': '10.1016/j.heliyon.2024.e39167_bib32',
'doi-asserted-by': 'crossref',
'DOI': '10.1172/jci.insight.124529',
'article-title': 'Fibulin-1c regulates transforming growth factor-beta activation in '
'pulmonary tissue fibrosis',
'volume': '5',
'author': 'Liu',
'year': '2019',
'journal-title': 'Jci Insight'},
{ 'issue': '7',
'key': '10.1016/j.heliyon.2024.e39167_bib33',
'doi-asserted-by': 'crossref',
'first-page': '817',
'DOI': '10.1002/mc.22531',
'article-title': 'Differential ability of formononetin to stimulate proliferation of '
'endothelial cells and breast cancer cells via a feedback loop involving '
'MicroRNA-375, RASD1, and ERα',
'volume': '57',
'author': 'Chen',
'year': '2018',
'journal-title': 'Mol. Carcinog.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib34',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.lfs.2022.120752',
'article-title': 'Naringenin: a potential flavonoid phytochemical for cancer therapy',
'volume': '305',
'author': 'Motallebi',
'year': '2022',
'journal-title': 'Life Sci.'},
{ 'issue': '12',
'key': '10.1016/j.heliyon.2024.e39167_bib35',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/polym13121943',
'article-title': 'Chemical modification of banana trunk fibers for the production of '
'green composites',
'volume': '13',
'author': 'Sathasivam',
'year': '2021',
'journal-title': 'Polymers'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib36',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.intimp.2020.106727',
'article-title': 'A network pharmacology strategy to investigate the anti-inflammatory '
'mechanism of luteolin combined with in vitro transcriptomics and '
'proteomics',
'volume': '86',
'author': 'Huang',
'year': '2020',
'journal-title': 'Int. Immunopharm.'},
{ 'issue': '20',
'key': '10.1016/j.heliyon.2024.e39167_bib37',
'doi-asserted-by': 'crossref',
'first-page': '10970',
'DOI': '10.1073/pnas.2005615117',
'article-title': 'Effective treatment of severe covid-19 patients with tocilizumab',
'volume': '117',
'author': 'Xu',
'year': '2020',
'journal-title': 'Proc. Natl. Acad. Sci. U. S. A.'},
{ 'issue': '6',
'key': '10.1016/j.heliyon.2024.e39167_bib38',
'article-title': 'The il-1beta, il-6, and tnf cytokine triad is associated with '
'post-acute sequelae of covid-19',
'volume': '3',
'author': 'Schultheiss',
'year': '2022',
'journal-title': 'Cell Rep. Med'},
{ 'issue': '9',
'key': '10.1016/j.heliyon.2024.e39167_bib39',
'doi-asserted-by': 'crossref',
'first-page': 'e2932',
'DOI': '10.1093/cid/ciaa1280',
'article-title': 'Viral dynamics and immune correlates of coronavirus disease 2019 '
'(covid-19) severity',
'volume': '73',
'author': 'Young',
'year': '2021',
'journal-title': 'Clin. Infect. Dis.'},
{ 'issue': '1',
'key': '10.1016/j.heliyon.2024.e39167_bib40',
'doi-asserted-by': 'crossref',
'first-page': '168',
'DOI': '10.1016/j.jhep.2020.09.031',
'article-title': 'Covid-19: discovery, diagnostics and drug development',
'volume': '74',
'author': 'Asselah',
'year': '2021',
'journal-title': 'J. Hepatol.'},
{ 'issue': '11',
'key': '10.1016/j.heliyon.2024.e39167_bib41',
'doi-asserted-by': 'crossref',
'first-page': '4045',
'DOI': '10.1007/s11010-021-04219-w',
'article-title': 'Role of pi3k/akt signaling pathway in cardiac fibrosis',
'volume': '476',
'author': 'Qin',
'year': '2021',
'journal-title': 'Mol. Cell. Biochem.'},
{ 'issue': '1',
'key': '10.1016/j.heliyon.2024.e39167_bib42',
'doi-asserted-by': 'crossref',
'first-page': '400',
'DOI': '10.1038/s41392-021-00788-w',
'article-title': 'Crosstalk between circrnas and the pi3k/akt signaling pathway in cancer '
'progression',
'volume': '6',
'author': 'Xue',
'year': '2021',
'journal-title': 'Signal Transduct. Targeted Ther.'},
{ 'key': '10.1016/j.heliyon.2024.e39167_bib43',
'doi-asserted-by': 'crossref',
'DOI': '10.3389/fphar.2021.754241',
'article-title': 'Phillyrin for covid-19 and influenza co-infection: a potential '
'therapeutic strategy targeting host based on bioinformatics analysis',
'volume': '12',
'author': 'Lai',
'year': '2021',
'journal-title': 'Front. Pharmacol.'},
{ 'issue': '18',
'key': '10.1016/j.heliyon.2024.e39167_bib44',
'doi-asserted-by': 'crossref',
'DOI': '10.1128/AEM.01350-18',
'article-title': 'Neospora caninum dense granule protein 7 regulates the pathogenesis of '
'neosporosis by modulating host immune response',
'volume': '84',
'author': 'Nishikawa',
'year': '2018',
'journal-title': 'Appl. Environ. Microbiol.'}],
'container-title': 'Heliyon',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S2405844024151985?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S2405844024151985?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2024, 10, 14]],
'date-time': '2024-10-14T02:53:50Z',
'timestamp': 1728874430000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S2405844024151985'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2024, 10]]},
'references-count': 44,
'journal-issue': {'issue': '20', 'published-print': {'date-parts': [[2024, 10]]}},
'alternative-id': ['S2405844024151985'],
'URL': 'http://dx.doi.org/10.1016/j.heliyon.2024.e39167',
'relation': {},
'ISSN': ['2405-8440'],
'subject': [],
'container-title-short': 'Heliyon',
'published': {'date-parts': [[2024, 10]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'Decoding the mechanism of Qingjie formula in the prevention of COVID-19 based '
'on network pharmacology and molecular docking',
'name': 'articletitle',
'label': 'Article Title'},
{'value': 'Heliyon', 'name': 'journaltitle', 'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.heliyon.2024.e39167',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{'value': '© 2024 Published by Elsevier Ltd.', 'name': 'copyright', 'label': 'Copyright'}],
'article-number': 'e39167'}
