文献类型：期刊文献

英文题名：Systematic Insight into the Dual Inhibitory Mechanism of Duhuo Jisheng Decoction Targeting Cox-2 and 5-Lox Against Osteoarthritis Based on in Silico and Bioassay Methods

作者：Zhang, Min[1]; Li, Yaling[2,3]; Liu, Hao[1]; Hao, Guoxiong[4]; Zhang, Huijuan[1]; Li, Mi[1,7]; Li, Chenghao[5]; Qiu, Lu[2]; Hou, Yehu[2]; Li, Jintian[3]; Xue, Weiwei[6]; Liu, Yongqi[2,3,7]; Jin, Xiaojie[1,2,3]

第一作者：张敏

机构：[1] College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China; [2] Gansu University, Key Laboratory for Molecular Medicine and Chinese Medicine Prevention and Treatment of Major Diseases, Gansu University of Chinese Medicine, Lanzhou, China; [3] Key Laboratory of Dunhuang Medicine, Ministry of Education, Gansu University of Chinese Medicine, Lanzhou, China; [4] Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, China; [5] Medical College, Yangzhou University, Yangzhou, China; [6] School of Pharmaceutical Sciences, Innovative Drug Research Centre, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, China; [7] Gansu University of Traditional Chinese Medicine, China

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2024

外文期刊名：SSRN

收录：EI(收录号：20240323679)

语种：英文

外文关键词：Binding energy - Diagnosis - Enzyme inhibition - Flavonoids - Free energy - Plants (botany)

摘要：Traditional Chinese medicine (TCM) is frequently used to treat osteoarthritis (OA). Duhuo Jisheng decoction (DHJSD), a Chinese patent medicine, was commonly used Chinese herbal formula for the treatment of OA. In Western medicine, dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme has been proved to be a promising strategy to treat inflammatory diseases with reduced side effects. This study aimed to elucidate the dual action mechanism of DHJSD targeting COX-2 and 5-LOX against OA. DHJSD, containing 1495 compounds was first screened using a virtual screening approach based on molecular docking, and 13 compounds were identified as promising candidates. Among these candidates, 7,4'-dimethoxyisoflavone, genistein, and fraxetin displayed both inhibition of COX-2 and 5-LOX. Further in vitro assay indicated that 7,4'-dimethoxyisoflavone, genistein, and fraxetin could inhibit inflammatory response and ameliorate cartilage degradation. The anti-inflammatory activity of the three compounds was further assessed using in vivo assay, and the results showed that the highest anti-inflammatory activity with edema inhibition percentages of 50.00 %, 56.00 %, and 51.00 % after 3 h, respectively. Moreover, it was found that 7,4'-dimethoxyisoflavone, genistein, and fraxetin have a superior gastric safety profile. Finally, molecular dynamics simulations, binding free energy analysis, and detailed interaction mode demonstrated that 7,4'-dimethoxyisoflavone, genistein, and fraxetin interacted well with both COX-2 and 5-LOX. Our results help to explain the dual action mechanism and potential material basis of DHJSD in treating OA and provide evidence to support DHJSD’s clinical use. ? 2024, The Authors. All rights reserved.