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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Oxymatrine-induced Apoptosis in Fibroblasts like Synoviocytes via Regulation of miR-146a/ TRAF6/JNK1 Axis in Rheumatoid Arthritis

Author(s): Jing Li and Hua Hong*

Volume 20, Issue 2, 2023

Published on: 13 December, 1901

Page: [232 - 237] Pages: 6

DOI: 10.2174/1570180819666220530143250

Price: $65

Abstract

Objective: Rheumatoid Arthritis (RA) is made when the synovial tissues and joints are destroyed by the inflammation refection, especially the chronic inflammation. The RA-FLS was treated with Oxymatrine, and the influence of miR-146a and TRAF6 /JNK pathway was explored.

Methods: Oxymatrine -treated RA-FLS were harvested to detect cell viability by CCK-8. The expression of miR-146a was detected by qRT-PCR. The expression of IRAK1, TRAF6, JNK1, and p-JNK1 was obtained by Western blot.

Results: The optimum oxymatrine concentration inhibiting RA-FLS was 4mg/ml at 48h. The expression of miR-146a at 48h and 72h was higher than 0 and 24h in RA-FLS treated with 4mg/ml oxymatrine. IRAK1, TRAF6, and p-JNK at 48h and 72h were lower than 0 and 24h in RA-FLS treated with 4mg/ml oxymatrine. When the miR-146a was inhibited, the expression of miR-146a was very low in the miR- 146a inhibitor group. No matter whether oxymatrine existed, the expression of IRAK1, TRAF6, and p- JNK in the miR-146a inhibitor group with or without oxymatrine was higher than the mock group, blank group, and only oxymatrine added group. The cell viability in the miR-146a inhibitor group and oxymatrine + miR-146a inhibitor group was higher than in the other groups. When IRAK1 was over expressed, the expression of miR-146a in the oxymatrine + IRAK1 overexpression group was higher than in the IRAK1 overexpression group. However, The expression of IRAK1, TRAF6, and p-JNK1 in the IRAK1 overexpression group with or without oxymatrine was higher than the pcDNA3.1 group, blank group, and only oxymatrine added group. The cell viability in the IRAK1 overexpression group and oxymatrine + IRAK1 overexpression group was higher than in the other groups.

Conclusion: Oxymatrine can inhibit RA-FLS proliferation via miR146a and IRAK1/TRAF6/JNK1 axis. Hence, oxymatrine may be a drug or adjuvant drug to treat RA in the future.

Keywords: Rheumatoid arthritis, oxymatrine, microRNA-146a, IRAK1/TRAF6/JNK1 axis, apoptosis, fibroblast

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Graphical Abstract

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