Phloridzin reduces synovial hyperplasia and inflammation in rheumatoid arthritis rat by modulating mTOR pathway.

Autor: Wang L; Department of Orthopedics, The Second People's Hospital of Nanyang City, Henan Province 473000, China. Electronic address: wangliuyu442@gmail.com., Wu X; Department of Orthopedics, The Second People's Hospital of Nanyang City, Henan Province 473000, China., Wan Q; Department of Orthopedics, The Second People's Hospital of Nanyang City, Henan Province 473000, China., Yang Y; Department of Orthopedics, The Second People's Hospital of Nanyang City, Henan Province 473000, China., Gao C; Department of Orthopedics, The Second People's Hospital of Nanyang City, Henan Province 473000, China.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 May 30; Vol. 133, pp. 111727. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1016/j.intimp.2024.111727
Abstrakt: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease and management of it still a challenge. Given report evaluates protective effect of phlorizin on RA and also postulates the molecular mechanism of its action. Bovine type II collagen (CIA) and Freund's incomplete adjuvant (1:1 and 1 mg/ml) was administered on 1st and 8th day of protocol to induce RA in rats and treatment with phlorizin 60 and 120 mg/kg was started after 4th week of protocol. Level of inflammatory cytokines and expression of proteins were estimated in phlorizin treated RA rats. Moreover in-vitro study was performed on Fibroblast-like synoviocytes (FLSs) and effect of phlorizin was estimated on proliferation, apoptosis and expression of mTOR pathway protein after stimulating these cell lines with Tumour Necrosis Factor alpha (TNF-α). Data of study suggest that phlorizin reduces inflammation and improves weight in CIA induced RA rats. Level of inflammatory cytokines in the serum and expression of Akt/PI3K/mTOR proteins in the join tissue was reduced in phlorizin treated RA rats. Phlorizin also reported to reverse the histopathological changes in the joint tissue of RA rats. In-vitro study supports that phlorizin reduces proliferation and no apoptotic effect on TNF-α stimulated FLSs. Expression of Akt/PI3K/mTOR proteins also downregulated in phlorizin treated TNF-α stimulated FLSs. In conclusion, phlorizin protects inflammation and reduces injury to the synovial tissues in RA, as it reduces autophagy by regulating Akt/PI3K/mTOR pathway.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE