1. Academic Validation
  2. Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis

Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis

  • Research (Wash D C). 2024 Sep 10:7:0459. doi: 10.34133/research.0459.
Qiuyan Guo 1 Qixin Wang 1 Jiayun Chen 1 Minghong Zhao 1 Tianming Lu 1 Zuchang Guo 1 Chen Wang 1 Yin Kwan Wong 2 Xueling He 1 Lin Chen 1 Wenjing Zhang 3 Chuanhao Dai 1 Shengnan Shen 1 Huanhuan Pang 1 Fei Xia 1 Chong Qiu 1 Daoyuan Xie 4 Jigang Wang 1 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
  • 2 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 3 Chinese Medical Association, Beijing 100710, China.
  • 4 Laboratory of Translational Medicine Research, Deyang People's Hospital of Chengdu University of Traditional Chinese Medicine, Deyang 618000, China.
  • 5 State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China.
  • 6 Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China.
Abstract

Rheumatoid arthritis (RA) is an autoimmune disease with features of synovial inflammation, cartilage erosion, bone destruction, and pain and is currently lacking a satisfactory treatment strategy. Dihydroartemisinin (DHA), the active metabolite of artemisinin, has exhibited outstanding suppressive effects on RA without obvious side effects. However, the underlying mechanisms remain unclear, which limits its further clinical application. The purpose of this study is to reveal the pharmacodynamic mechanism of DHA against RA by means of a combination of single-cell RNA Sequencing (RNA-seq), proteomics, as well as transcriptomics both in vivo and in vitro. In our results, DHA effectively reduced the degree of redness, swelling, and pain in RA rats and dramatically changed the synovial tissue microenvironment under the pathological state. Within this microenvironment, fibroblasts, macrophages, B cells, and endothelial cells were the major affected cell types, primarily through DHA targeting the extracellular matrix (ECM) structural constituent signaling pathway. In addition, we confirmed that DHA regulated the ECM by modulating matrix metalloproteinase 2 (MMP2) and MMP3 in the synovial tissue of RA rats. Moreover, DHA induced Apoptosis in MH7A cells, further validating the bioinformatics data. In conclusion, DHA effectively reduced the inflammatory response and improved the immune microenvironment in synovial tissue by inhibiting MMP2 and MMP3. Our findings provide a basis for the application of DHA in the treatment of RA.

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