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As part of the Aconitum species, Benzoylaconitine (BAC) shows potential antiviral, anti-tumor, and anti-inflammatory effects. In this study, we investigated the effects and mechanisms of BAC on tumor necrosis factor-alpha (TNF-\u03b1)\/LPS-induced HaCaT keratinocytes in a imiquimod(IMQ)-induced mice model. The results showed that BAC could relieve the symptoms of psoriasis by inhibiting cell proliferation, the release of inflammatory factors, and the accumulation of Th17 cells, while no obvious effect on cell viability and safety was observed both in vitro and in vivo. Additionally, BAC can markedly inhibit the protein and mRNA levels of inflammatory cytokines in TNF-\u03b1\/LPS-induced HaCaT keratinocytes by inhibiting the phosphorylation of STAT3. In brief, our data indicated that BAC could alleviate the progression of psoriasis and may be a potential therapeutic agent for treating psoriasis in clinical practice.<\/jats:p>","DOI":"10.3390\/molecules28114473","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T02:39:47Z","timestamp":1685587187000},"page":"4473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Benzoylaconitine Alleviates Progression of Psoriasis via Suppressing STAT3 Phosphorylation in Keratinocytes"],"prefix":"10.3390","volume":"28","author":[{"given":"Yuanbo","family":"Li","sequence":"first","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Neurobiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Guo","sequence":"additional","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aifang","family":"Li","sequence":"additional","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sugai","family":"Yin","sequence":"additional","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6222-4323","authenticated-orcid":false,"given":"Shuxuan","family":"Li","sequence":"additional","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Li","sequence":"additional","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-361X","authenticated-orcid":false,"given":"Tao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2466-4912","authenticated-orcid":false,"given":"Shuying","family":"Feng","sequence":"additional","affiliation":[{"name":"Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1007\/s00204-016-1782-z","article-title":"A protocol to determine dermal absorption of xenobiotica through human skin in vitro","volume":"91","author":"Fabian","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.amepre.2014.02.012","article-title":"Prevalence of psoriasis among adults in the US 2003\u20132006 and 2009\u20132010 national health and nutrition examination surveys","volume":"4","author":"Helmick","year":"2014","journal-title":"Am. J. Prev. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000495291","article-title":"Psoriasis: Keratinocytes or immune cells-which is the trigger?","volume":"235","author":"Benhadou","year":"2019","journal-title":"Dermatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.jid.2019.01.026","article-title":"Psoriasis pathogenesis: Keratinocytes are back in the spotlight","volume":"139","author":"Eyerich","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/jdv.13854","article-title":"A systematic review of worldwide epidemiology of psoriasis","volume":"31","author":"Michalek","year":"2017","journal-title":"J. Eur. Acad. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"122591","DOI":"10.1016\/j.ijpharm.2023.122591","article-title":"Microneedles as a momentous platform for psoriasis therapy and diagnosis: A state-of-the-art review","volume":"632","author":"Gowd","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mortier, C., Gracey, E., Coudenys, J., Manuello, T., Decruy, T., Maelegheer, M., Stappers, F., Gilis, E., Gaublomme, D., and Van Hoorebeke, L. (2023). ROR\u03b3t inhibition ameliorates IL-23 driven experimental psoriatic arthritis by predominantly modulating \u03b3\u03b4-T cells. Rheumatology, kead022.","DOI":"10.1093\/rheumatology\/kead022"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41392-022-01219-0","article-title":"Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.jid.2019.01.006","article-title":"Imiquimod-induced psoriasis in mice depends on the IL-17 signaling of keratinocytes","volume":"139","author":"Moos","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/BOR.0000000000000358","article-title":"Pathogenesis and immunotherapy in cutaneous psoriasis: What can rheumatologists learn?","volume":"29","author":"Alexander","year":"2017","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cintra, G.A.D., Pinto, L.A., Calixto, G.M.F., Soares, C.P., Von Zuben, E.D., Scarpa, M.V., Gremiao, M.P.D., and Chorilli, M. (2016). Bioadhesive surfactant systems for methotrexate skin delivery. Molecules, 21.","DOI":"10.3390\/molecules21020231"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","article-title":"Psoriasis","volume":"386","author":"Boehncke","year":"2015","journal-title":"Lancet"},{"key":"ref_13","first-page":"1241","article-title":"The HLA-Cw*06 allele may predict the response to methotrexate (MTX) treatment in Chinese arthritis-free psoriasis patients","volume":"315","author":"Mao","year":"2022","journal-title":"Arch. Dermatol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jhep.2022.12.034","article-title":"Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated","volume":"78","author":"Atallah","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhao, G., Han, K., Sun, D., Zhou, N., Song, Z., Liu, H., Li, J., and Li, G. (2022). Applications of molecular imprinting technology in the study of traditional Chinese medicine. Molecules, 28.","DOI":"10.3390\/molecules28010301"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"841435","DOI":"10.3389\/fphar.2022.841435","article-title":"A novel modulator of the renin-angiotensin system, benzoylaconitine, attenuates hypertension by targeting ACE\/ACE2 in enhancing vasodilation and alleviating vascular inflammation","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_17","first-page":"5523870","article-title":"Traditional Chinese medicine aconiti radix cocta improves rheumatoid arthritis via suppressing COX-1 and COX-2","volume":"2021","author":"Li","year":"2021","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jff.2017.03.039","article-title":"Liquiritin, a flavone compound from licorice, inhibits IL-1 beta-induced inflammatory responses in SW982 human synovial cells","volume":"33","author":"Gao","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1007\/s10753-021-01478-z","article-title":"Benzoylaconine modulates LPS-induced responses through inhibition of Toll-like receptor-mediated NF-\u03baB and MAPK signaling in RAW264.7 cells","volume":"44","author":"Zhou","year":"2021","journal-title":"Inflammation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/ptr.5316","article-title":"Review of clinical pharmacology of aloe vera L. in the treatment of psoriasis","volume":"29","author":"Miroddi","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1196\/annals.1443.021","article-title":"Regulation and function of proinflammatory TH17 cells","volume":"1143","author":"Martinez","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/ni1497","article-title":"Development, cytokine profile and function of human interleukin 17-producing helper T cells","volume":"8","author":"Wilson","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1111\/jdv.14433","article-title":"The role of IL-23 and the IL-23\/T(H)17 immune axis in the pathogenesis and treatment of psoriasis","volume":"31","author":"Girolomoni","year":"2017","journal-title":"J. Eur. Acad. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/gerona\/glac118","article-title":"Anti-inflammatory and chondroprotective effects of platelet-derived growth factor-BB on osteoarthritis rat models","volume":"78","author":"Cai","year":"2022","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1050373","DOI":"10.3389\/fimmu.2022.1050373","article-title":"Paradoxical phenomena of bullous pemphigoid induced and treated by identical biologics","volume":"13","author":"Zhang","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev-pathol-011811-132448","article-title":"Psoriasis","volume":"7","author":"Perera","year":"2012","journal-title":"Annu. Rev. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17588359221148536","DOI":"10.1177\/17588359221148536","article-title":"Renal impairment and abnormal liver function tests in pre-therapeutic phenotype-based DPD deficiency screening using uracilemia: A comprehensive population-based study in 1138 patients","volume":"15","author":"Callon","year":"2023","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1038\/sj.onc.1203551","article-title":"Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL -6 family of cytokine receptors","volume":"19","author":"Hirano","year":"2000","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.1007\/s12325-021-01795-7","article-title":"Real-world claims analyses of comorbidity burden, treatment pattern, healthcare resource utilization, and costs in pediatric psoriasis","volume":"38","author":"Anderson","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_30","first-page":"3537","article-title":"Effects of aloe polysaccharide, a polysaccharide extracted from Aloe vera, on TNF-alpha-induced HaCaT cell proliferation and the underlying mechanism in psoriasis","volume":"18","author":"Leng","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1080\/00498254.2020.1866229","article-title":"Comparative HPLC-MS\/MS-based pharmacokinetic studies of multiple diterpenoid alkaloids following the administration of Zhenwu Tang and Radix Aconiti Lateralis Praeparata extracts to rats","volume":"51","author":"Liu","year":"2021","journal-title":"Xenobiotica"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/jid.2012.339","article-title":"Global Epidemiology of Psoriasis: A Systematic Review of Incidence and Prevalence","volume":"133","author":"Parisi","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1055\/s-0042-115177","article-title":"Topically used herbal products for the treatment of psoriasis-mechanism of action, Drug Delivery, Clinical Studies","volume":"82","author":"Herman","year":"2016","journal-title":"Planta. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"599947","DOI":"10.3389\/fimmu.2020.599947","article-title":"Interleukin 17 promotes expression of alarmins S100A8 and S100A9 during the inflammatory response of keratinocytes","volume":"11","author":"Christmann","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/08923970802135161","article-title":"Thalidomide suppressed IL-1 beta while enhancing TNF-alpha and IL-10, when cells in whole blood were stimulated with lipopolysaccharide","volume":"30","author":"Shannon","year":"2008","journal-title":"Immunopharm. Immunot."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"560579","DOI":"10.3389\/fmed.2020.560579","article-title":"Polyethylene glycol ointment alleviates psoriasis-like inflammation through down-Regulating the Function of Th17 Cells and MDSCs","volume":"7","author":"Lu","year":"2021","journal-title":"Front. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"106767","DOI":"10.1016\/j.intimp.2020.106767","article-title":"Hispidulin alleviates imiquimod-induced psoriasis-like skin inflammation by inhibiting splenic Th1\/Th17 cell population and keratinocyte activation","volume":"87","author":"Kim","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jdermsci.2020.05.013","article-title":"Facile skin targeting of a thalidomide analog containing benzyl chloride moiety alleviates experimental psoriasis via the suppression of MAPK\/NF-kappa B\/AP-1 phosphorylation in keratinocytes","volume":"99","author":"Tang","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nm1162","article-title":"Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model","volume":"11","author":"Sano","year":"2005","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2020.01899","article-title":"Differential response of gestational tissues to TLR3 Viral Priming Prior to Exposure to Bacterial TLR2 and TLR2\/6 Agonists","volume":"11","author":"Rasheed","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.immuni.2011.10.006","article-title":"Pivotal role of dermal IL-17-producing gamma delta T cells in skin inflammation","volume":"35","author":"Cai","year":"2011","journal-title":"Immunity"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/11\/4473\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:46:32Z","timestamp":1760125592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/11\/4473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["molecules28114473"],"URL":"https:\/\/doi.org\/10.3390\/molecules28114473","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]}}}