The active ingredient of Evodia rutaecarpa reduces inflammation in knee osteoarthritis rats through blocking calcium influx and NF-κB pathway.

Autor: Gao Y; National Innovation and Attracting Talents '111' base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China., Wang S; National Innovation and Attracting Talents '111' base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China., Gao Y; College of Biology and Environmental Sciences, Jishou University, Jishou, China., Yang L; National Innovation and Attracting Talents '111' base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Jazyk: angličtina
Zdroj: Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2024 Dec; Vol. 135 (6), pp. 705-719. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1111/bcpt.14096
Abstrakt: Chronic inflammation significantly contributes to the progression of osteoarthritis (OA), and an anti-inflammatory small molecule derived from medicinal herbs could be a potential drug candidate for OA. Herein, we investigated the function and mechanism of Evodiamine (EAE), the active ingredient from Evodia rutaecarpa, in chondrocytes and macrophages in vitro and in vivo. The cytotoxicity of EAE was determined using an MTT assay. And the anti-inflammatory and anti-extracellular matrix (ECM) degradation effects of EAE were investigated using qRT-PCR, western blot (WB), immunofluorescence (IF). Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), Fluo-4 AM, IF and AutoDock were used to elucidate the molecular mechanisms and signalling pathways of the reducing-inflammatory properties of EAE on chondrocytes in vitro. Moreover, the effect of EAE on macrophage polarization was detected by IF and flow cytometry (FC). Ultimately, we explored the in vivo therapeutic efficacy of EAE in an anterior cruciate ligament transection (ACLT)-induced OA model. The finding demonstrated that EAE blocked the phosphorylation of IKBα and Ca 2+ influx, thereby curbing inflammation and ECM degradation. Additionally, EAE can prevent the polarization towards the M1 phenotype. Thus, our findings suggest that EAE has great potential as a therapeutic drug for the treatment of OA.
(© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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