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This study aims to reveal the pharmacological effects of kaempferol, which is the active component of <jats:italic>Radix Bupleuri<\/jats:italic> and <jats:italic>Tripterygii Radix<\/jats:italic>, and potential mechanisms for the treatment of COVID\u201019. Here, we employed the bioinformatics methods to filter the anti\u2010COVID\u201019 candidate genes of kaempferol, which mainly enriched in inflammation (TNF, JUN, etc.) and virus infection (AKT1, JNK, etc.). The Transcription levels of AKT1, JNK and JUN were significantly reduced by kaempferol treatment in the LPS\u2010activated macrophages. In addition, kaempferol reduced the secretion of inflammatory factors by LPS\u2010stimulated macrophages, inhibited MAPK\/NF\u2010\u03baB signaling and regulated macrophage polarization to M2 type in vitro, and suppressed endotoxin\u2010induced cytokine storm and improved survival in mice. Molecular docking analysis demonstrated that kaempferol was probable to bind the COVID\u201019 protein 5R84 and formatted hydrogen bond with the residues, the free binding energy of which was lower than the original ligand. In summary, our current work indicates that kaempferol has anti\u2010COVID\u201019 potential through the reduction of COVID\u201019\u2010induced body dysfunction and molecule\u2013protein interaction, and bioinformatics results clarify that some of these key target genes might serve as potential molecular markers for detecting COVID\u201019.<\/jats:p>","DOI":"10.1002\/ptr.7740","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T05:50:22Z","timestamp":1675317022000},"page":"2290-2304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Kaempferol has potential anti\u2010coronavirus disease 2019 (<scp>COVID<\/scp>\u201019) targets based on bioinformatics analyses and pharmacological effects on endotoxin\u2010induced cytokine storm"],"prefix":"10.1002","volume":"37","author":[{"given":"Yaoxiang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory The Affiliated Yixing Hospital of Jiangsu University  Yixing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Tao","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Arts &amp; Science Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Affiliated Yixing Hospital of Jiangsu University  Yixing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Affiliated Yixing Hospital of Jiangsu University  Yixing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Affiliated Yixing Hospital of Jiangsu University  Yixing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-2659","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Jiangsu Province hospital on Integration of Chinese and Western Medicine Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1559325820982423"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.01.042"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13122418"},{"issue":"1","key":"e_1_2_9_5_1","first-page":"146","article-title":"Kaempferol suppresses acetaminophen\u2010induced liver damage by upregulation\/activation of SIRT1","volume":"59","author":"Bin Mowyna M. 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