PMID- 31181689 OWN - NLM STAT- MEDLINE DCOM- 20191125 LR - 20200225 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 24 IP - 11 DP - 2019 Jun 7 TI - Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8-MyD88-NF-kappaB-NLRP3 Inflammasome Pathway. LID - 10.3390/molecules24112157 [doi] LID - 2157 AB - BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. Datura metel L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear. METHODS: An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of Datura metel L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7- myeloid differentiation primary response gene 88-nuclear Factor-kappaB-nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8-MyD88-NF-kappaB-NLRP3) inflammasome pathway. RESULTS: EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1beta, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1), and interferon-gamma (IFN-gamma). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKalpha, p-IKBalpha, p-NF-kappaB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1beta. CONCLUSION: This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8-MyD88-NF-kappab-NLRP3 inflammasome pathway. FAU - Yang, Bing-You AU - Yang BY AD - Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China. yangbingyou@hljucm.net. FAU - Cheng, Yan-Gang AU - Cheng YG AD - Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China. chengyg1992@163.com. FAU - Liu, Yan AU - Liu Y AD - Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China. lifeliuyan@hljucm.net. FAU - Liu, Yuan AU - Liu Y AD - Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China. flyliuyuan@163.com. FAU - Tan, Jin-Yan AU - Tan JY AD - Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China. 15636833827@163.com. FAU - Guan, Wei AU - Guan W AD - Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China. myguanwei1234@yeah.net. FAU - Guo, Shuang AU - Guo S AD - Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China. 18231176108@163.com. FAU - Kuang, Hai-Xue AU - Kuang HX AD - Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China. hxkuang@yahoo.com. LA - eng GR - 81773883/NSFC/ GR - 2018yjscx003/Heilongjiang university of chinses medicine/ PT - Journal Article DEP - 20190607 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Cytokines) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Membrane Glycoproteins) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 0 (TLR8 protein, mouse) RN - 0 (Tlr7 protein, mouse) RN - 0 (Toll-Like Receptor 7) RN - 0 (Toll-Like Receptor 8) RN - P1QW714R7M (Imiquimod) SB - IM MH - Animals MH - Cytokines/*metabolism MH - Datura metel/*chemistry MH - Disease Models, Animal MH - Down-Regulation MH - Drugs, Chinese Herbal/*administration & dosage/pharmacology MH - Gene Expression Regulation/drug effects MH - Imiquimod/*adverse effects MH - Male MH - Membrane Glycoproteins/metabolism MH - Mice MH - Myeloid Differentiation Factor 88/metabolism MH - NF-kappa B/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Psoriasis/chemically induced/*drug therapy/immunology MH - Signal Transduction/*drug effects MH - Toll-Like Receptor 7/metabolism MH - Toll-Like Receptor 8/metabolism PMC - PMC6600670 OTO - NOTNLM OT - Datura metel L. OT - imiquimod OT - inflammatory cytokines OT - psoriasis OT - toll-like receptor 7/8 COIS- The authors declare that there are no conflicts of interest. EDAT- 2019/06/12 06:00 MHDA- 2019/11/26 06:00 PMCR- 2019/06/07 CRDT- 2019/06/12 06:00 PHST- 2019/05/08 00:00 [received] PHST- 2019/05/30 00:00 [revised] PHST- 2019/06/06 00:00 [accepted] PHST- 2019/06/12 06:00 [entrez] PHST- 2019/06/12 06:00 [pubmed] PHST- 2019/11/26 06:00 [medline] PHST- 2019/06/07 00:00 [pmc-release] AID - molecules24112157 [pii] AID - molecules-24-02157 [pii] AID - 10.3390/molecules24112157 [doi] PST - epublish SO - Molecules. 2019 Jun 7;24(11):2157. doi: 10.3390/molecules24112157.