文献类型：期刊文献

英文题名：Octahydroindolizine alkaloid Homocrepidine A from Dendrobium crepidatum attenuate P. acnes-induced inflammatory in vitro and in vivo

作者：Gong, Lizhi[1];Xu, Jiayao[1];Guo, Miaomiao[4];Zhao, Jian[1];Xin, Xiujuan[1];Zhang, Chaofeng[5];Ni, Xiaoming[1];Hu, Yang[2];An, Faliang[1,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Peoples R China;[3]Marine Biomed Sci & Technol Innovat Platform Lin g, 4 Lane 218,Haiji Sixth Rd, Shanghai 201306, Peoples R China;[4]Beijing Technol & Business Univ, Key Lab Cosmet, China Natl Light Ind, 11-33 Fucheng Rd, Beijing 100048, Peoples R China;[5]China Pharmaceut Univ, Nanjing 211198, Peoples R China

年份：2024

卷号：333

外文期刊名：JOURNAL OF ETHNOPHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001258624900001)】；

基金：This work was financially supported by the National Key R & D Pro- gram of China (2023YFA0914102, 2023YFC2308200) , and National Natural Science Foundation (81803391) . We sincerely thank Prof. Jian Li, Xiaoming Ni, and Jiqun Wang (East China University of Science and Technology) for their help in this research.

语种：英文

外文关键词：Dendrobium crepidatum; Anti-inflammatory; TLR2; NLRP3; P. acnes

摘要：Ethnopharmacological relevance: Dendrobium crepidatum Lindl. ex Paxton is a perennial epiphyte of Dendrobium genus, distributed in southern China, and utilized as the traditional Chinese medicine "Shihu" in Yunnan Province. Due to its heat -clearing and detoxicating properties, it is formulated as the "XiaoCuoWan" as recorded in the China Pharmacopoeia, and specially used to treat chronic skin inflammatory diseases, such as acne. Aim of the study: This research aimed to estimate impact of the octahydroindoline alkaloid Homocrepidine A (HCA), isolated from D. crepidatum , on acne inflammation using both human THP-1 cells and mouse models. Furthermore, the potential anti-inflammatory mechanism of HCA has been analyzed through molecular biology methods and computer simulation. Materials and methods: THP-1 cells and mouse models induced by live Propionibacterium acnes ( P. acnes ) were employed to evaluate the anti-inflammatory properties of crude extract of D. crepidatum (DCE) and HCA. ELISA was utilized to detect the release of inflammatory cytokines in both cellular and murine ear tissues. RNAseq was used to screen the pathways associated with HCA-mediated inflammatory inhibition, while Western blot, RTqPCR, and immunofluorescence were utilized to detect the expression of relevant proteins. Additionally, molecular docking simulations and cellular thermal shift assays were employed to confirm the target of HCA. Results: Our research shows that DCE and HCA can effectively alleviate acne inflammation. HCA inhibits TLR2 expression by interacting with amino acid residues in the TIR domain of hTLR2, including Pro -681, Asn-688, Trp684, and Ile -685. Moreover, HCA disrupts inflammatory signal transduction mediated by MAPK and NF-kappa B pathways through MyD88-dependent pathway. Additionally, HCA treatment facilitates Nrf2 nuclear translocation and upregulates HO -1 expression, thereby inhibiting NLRP3 inflammasomes activation. In vivo experiments further revealed that HCA markedly attenuated erythema and swelling caused by P. acnes in mice ears, while also decreasing the expression of pro -inflammatory cytokines IL -18 and IL -8. Conclusions: Our research highlights the protective effects of D. crepidatum and its bioactive compound HCA against acne inflammation, marking the first exploration of its potential in this context. The discoveries indicate that HCA treatment may represent a promising functional approach for acne therapy.