{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T07:49:31Z","timestamp":1794383371133,"version":"4.9.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Chinese Academy of Sciences (CAS) Pioneer Hundred Talents Program"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-95994-9","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T15:53:41Z","timestamp":1743522821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Quantitative analysis of drug\u2013drug interactions among active components of Xuebijing in inhibiting LPS-induced TLR4 signaling and NO production"],"prefix":"10.1038","volume":"15","author":[{"given":"Tianshu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"95994_CR1","doi-asserted-by":"crossref","first-page":"917975","DOI":"10.3389\/fphar.2022.917975","volume":"13","author":"Y Wang","year":"2022","unstructured":"Wang, Y. et al. Traditional Chinese medicine in the treatment of chronic kidney diseases: Theories, applications, and mechanisms. Front. Pharmacol. 13, 917975 (2022).","journal-title":"Front. Pharmacol."},{"key":"95994_CR2","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1002\/med.21793","volume":"41","author":"R Fu","year":"2021","unstructured":"Fu, R. et al. The Yin and Yang of traditional Chinese and Western medicine. Med. Res. Rev. 41, 3182\u20133200 (2021).","journal-title":"Med. Res. Rev."},{"key":"95994_CR3","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.apsb.2020.06.009","volume":"10","author":"L Ni","year":"2020","unstructured":"Ni, L. et al. Combating COVID-19 with integrated traditional Chinese and western medicine in China. Acta Pharm. Sin B 10, 1149\u20131162 (2020).","journal-title":"Acta Pharm. Sin B"},{"key":"95994_CR4","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1002\/med.21963","volume":"43","author":"W Zhao","year":"2023","unstructured":"Zhao, W. et al. Advances of antitumor drug discovery in traditional Chinese medicine and natural active products by using multi-active components combination. Med. Res. Rev. 43, 1778\u20131808 (2023).","journal-title":"Med. Res. Rev."},{"key":"95994_CR5","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.apsb.2019.06.003","volume":"9","author":"J Li","year":"2019","unstructured":"Li, J. et al. High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care. Acta Pharm. Sin B 9, 1035\u20131049 (2019).","journal-title":"Acta Pharm. Sin B"},{"key":"95994_CR6","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1001\/jamainternmed.2023.0780","volume":"183","author":"S Liu","year":"2023","unstructured":"Liu, S. et al. Effect of an Herbal-Based injection on 28-Day mortality in patients with sepsis: The EXIT-SEP randomized clinical trial. JAMA Intern. Med. 183, 647\u2013655 (2023).","journal-title":"JAMA Intern. Med."},{"key":"95994_CR7","doi-asserted-by":"crossref","first-page":"627751","DOI":"10.3389\/fphar.2021.627751","volume":"12","author":"J Guo","year":"2021","unstructured":"Guo, J., Zhu, J., Wang, Q., Wang, J. & Jia, Y. Comparative efficacy of seven kinds of Chinese medicine injections in acute lung injury and acute respiratory distress syndrome: A network Meta-analysis of randomized controlled trials. Front. Pharmacol. 12, 627751 (2021).","journal-title":"Front. Pharmacol."},{"key":"95994_CR8","doi-asserted-by":"crossref","first-page":"899753","DOI":"10.3389\/fsurg.2022.899753","volume":"9","author":"Y Su","year":"2022","unstructured":"Su, Y., Zhang, Y., Yuan, H. & Shen, C. Efficacy of Xuebijing combined with ulinastatin in the treatment of traumatic sepsis and effects on inflammatory factors and immune function in patients. Front. Surg. 9, 899753 (2022).","journal-title":"Front. Surg."},{"key":"95994_CR9","first-page":"658","volume":"36","author":"RQ Yao","year":"2020","unstructured":"Yao, R. Q. et al. Influence of Xuebijing injection and its component paeoniflorin on immune function and survival rate of septic rats. Zhonghua Shao Shang Za Zhi 36, 658\u2013664 (2020).","journal-title":"Zhonghua Shao Shang Za Zhi"},{"key":"95994_CR10","doi-asserted-by":"crossref","first-page":"107918","DOI":"10.1016\/j.pharmthera.2021.107918","volume":"228","author":"C Lin","year":"2021","unstructured":"Lin, C. et al. TLR4 biased small molecule modulators. Pharmacol. Ther. 228, 107918 (2021).","journal-title":"Pharmacol. Ther."},{"key":"95994_CR11","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1021\/acs.accounts.9b00631","volume":"53","author":"Y Wang","year":"2020","unstructured":"Wang, Y. et al. Small-molecule modulators of Toll-like receptors. Acc. Chem. Res. 53, 1046\u20131055 (2020).","journal-title":"Acc. Chem. Res."},{"key":"95994_CR12","doi-asserted-by":"crossref","first-page":"15256","DOI":"10.1038\/s41598-022-19614-6","volume":"12","author":"Y Wang","year":"2022","unstructured":"Wang, Y. et al. Toll-like receptor 4-mediated endoplasmic reticulum stress induces intestinal paneth cell damage in mice following CLP-induced sepsis. Sci. Rep. 12, 15256 (2022).","journal-title":"Sci. Rep."},{"key":"95994_CR13","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.3892\/ijmm.2014.1943","volume":"34","author":"MW Liu","year":"2014","unstructured":"Liu, M. W., Wang, Y. H., Qian, C. Y. & Li, H. Xuebijing exerts protective effects on lung permeability leakage and lung injury by upregulating toll-interacting protein expression in rats with sepsis. Int. J. Mol. Med. 34, 1492\u20131504 (2014).","journal-title":"Int. J. Mol. Med."},{"key":"95994_CR14","doi-asserted-by":"crossref","first-page":"8501","DOI":"10.18632\/aging.204990","volume":"15","author":"XF Kang","year":"2023","unstructured":"Kang, X. F. et al. Xuebijing injection protects sepsis induced myocardial injury by mediating TLR4\/NF-kappaB\/IKKalpha and JAK2\/STAT3 signaling pathways. Aging (Albany NY) 15, 8501\u20138517 (2023).","journal-title":"Aging (Albany NY)"},{"key":"95994_CR15","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/s41586-022-04793-z","volume":"606","author":"JA Osterhout","year":"2022","unstructured":"Osterhout, J. A. et al. A preoptic neuronal population controls fever and appetite during sickness. Nature 606, 937\u2013944 (2022).","journal-title":"Nature"},{"key":"95994_CR16","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/s41380-021-01327-3","volume":"27","author":"W Li","year":"2022","unstructured":"Li, W. et al. Anti-depressive-like behaviors of APN KO mice involve Trkb\/BDNF signaling related neuroinflammatory changes. Mol. Psychiatry 27, 1047\u20131058 (2022).","journal-title":"Mol. Psychiatry"},{"key":"95994_CR17","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41374-018-0021-z","volume":"98","author":"Y Takatani","year":"2018","unstructured":"Takatani, Y. et al. Inducible nitric oxide synthase during the late phase of sepsis is associated with hypothermia and immune cell migration. Lab. Invest. 98, 629\u2013639 (2018).","journal-title":"Lab. Invest."},{"key":"95994_CR18","doi-asserted-by":"crossref","first-page":"172710","DOI":"10.1016\/j.ejphar.2019.172710","volume":"864","author":"J Zhang","year":"2019","unstructured":"Zhang, J., Zhang, Q., Liu, G. & Zhang, N. Therapeutic potentials and mechanisms of the Chinese traditional medicine Danshensu. Eur. J. Pharmacol. 864, 172710 (2019).","journal-title":"Eur. J. Pharmacol."},{"key":"95994_CR19","doi-asserted-by":"crossref","first-page":"103029","DOI":"10.1016\/j.redox.2024.103029","volume":"69","author":"Y Fu","year":"2024","unstructured":"Fu, Y. et al. Salvianolic acid B attenuates liver fibrosis by targeting Ecm1 and inhibiting hepatocyte ferroptosis. Redox Biol. 69, 103029 (2024).","journal-title":"Redox Biol."},{"key":"95994_CR20","doi-asserted-by":"crossref","first-page":"115972","DOI":"10.1016\/j.ejmech.2023.115972","volume":"263","author":"J Liu","year":"2024","unstructured":"Liu, J. et al. Novel ligustilide derivatives target quorum sensing system LasR\/LasB and relieve inflammatory response against Pseudomonas aeruginosa infection. Eur. J. Med. Chem. 263, 115972 (2024).","journal-title":"Eur. J. Med. Chem."},{"key":"95994_CR21","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3389\/fphar.2020.00482","volume":"11","author":"K Yan","year":"2020","unstructured":"Yan, K. et al. Safflower yellow and its main component HSYA alleviate diet-Induced obesity in mice: Possible involvement of the increased antioxidant enzymes in liver and adipose tissue. Front. Pharmacol. 11, 482 (2020).","journal-title":"Front. Pharmacol."},{"key":"95994_CR22","doi-asserted-by":"crossref","first-page":"614024","DOI":"10.3389\/fphar.2020.614024","volume":"11","author":"XT Wang","year":"2020","unstructured":"Wang, X. T. et al. Paeoniflorin and hydroxysafflor yellow A in Xuebijing injection attenuate sepsis-Induced cardiac dysfunction and inhibit proinflammatory cytokine production. Front. Pharmacol. 11, 614024 (2020).","journal-title":"Front. Pharmacol."},{"key":"95994_CR23","doi-asserted-by":"crossref","first-page":"1104243","DOI":"10.3389\/fphar.2023.1104243","volume":"14","author":"S Li","year":"2023","unstructured":"Li, S. et al. Suxiao Jiuxin pill attenuates acute myocardial ischemia via regulation of coronary artery tone. Front. Pharmacol. 14, 1104243 (2023).","journal-title":"Front. Pharmacol."},{"key":"95994_CR24","first-page":"465","volume":"27","author":"J Gao","year":"2015","unstructured":"Gao, J. et al. A prospective multicenter clinical study of Xuebijing injection in the treatment of sepsis and multiple organ dysfunction syndrome. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 27, 465\u2013470 (2015).","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"95994_CR25","first-page":"0141","volume":"6","author":"X Luan","year":"2023","unstructured":"Luan, X., Zhang, X., Nie, M. & Zhao, Y. Traditional Chinese medicine integrated responsive microneedles for systemic sclerosis treatment. Research (Wash D C) 6, 0141 (2023).","journal-title":"Research (Wash D C)"},{"key":"95994_CR26","doi-asserted-by":"crossref","first-page":"100915","DOI":"10.1016\/j.jpha.2023.12.005","volume":"14","author":"B Li","year":"2024","unstructured":"Li, B. et al. Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling. J. Pharm. Anal. 14, 100915 (2024).","journal-title":"J. Pharm. Anal."},{"key":"95994_CR27","doi-asserted-by":"crossref","first-page":"752","DOI":"10.2174\/1573409919666230519121138","volume":"20","author":"J Wang","year":"2024","unstructured":"Wang, J., Luo, C., Luo, M., Zhou, S. & Kuang, G. Targets and mechanisms of Xuebijing in the treatment of acute kidney injury associated with sepsis: A network pharmacology-based study. Curr. Comput. Aided Drug Des. 20, 752\u2013763 (2024).","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"95994_CR28","first-page":"100111","volume":"2","author":"H Li","year":"2021","unstructured":"Li, H. et al. Nicotine and its metabolite cotinine target MD2 and inhibit TLR4 signaling. Innovation (Camb) 2, 100111 (2021).","journal-title":"Innovation (Camb)"},{"key":"95994_CR29","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","volume":"58","author":"TC Chou","year":"2006","unstructured":"Chou, T. C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol. Rev. 58, 621\u2013681 (2006).","journal-title":"Pharmacol. Rev."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95994-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95994-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95994-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T20:43:03Z","timestamp":1743626583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95994-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["95994"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-95994-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]},"assertion":[{"value":"30 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This article does not contain any study with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statements"}}],"article-number":"11103"}}