Rutin inhibited the advanced glycation end products-stimulated inflammatory response and extra-cellular matrix degeneration. - GreenMedInfo Summary
Rutin inhibited the advanced glycation end products-stimulated inflammatory response and extra-cellular matrix degeneration via targeting TRAF-6 and BCL-2 proteins in mouse model of osteoarthritis.
Aging (Albany NY). 2021 09 22 ;13(18):22134-22147. Epub 2021 Sep 22. PMID: 34550907
Xiang Chen
BACKGROUND: Osteoarthritis (OA) is degenerative joint disorder mainly characterized by long-term pain with limited activity of joints, the disease has no effective preventative therapy. Rutin (RUT) is a flavonoid compound, present naturally. The flavonoid shows range of biological activities such as anti-inflammatory and anti-cancer effect. We screened RUT for its activity against osteoarthritis withandmodels of osteoarthritis.
METHODS: Animal model of OA was developed using C57BL/6 mice by surgical destabilization of medial meniscus. Forstudies the human articular cartilage tissues were used which were collected from osteoarthritis patients and were processed to isolate chondrocytes. The chondrocytes were submitted to advanced glycation end products (AGEs) for inducing osteoarthritis. Cell viability was done by CCK-8 assay, ELISA analysis for MMP13, collage II, PGE2, IL-6, TNF-α, ADAMTS-5 and MMP-13. Western blot analysis was done for expression of proteins andanalysis was done by docking studies.
RESULTS: Pretreatment of RT showed no cytotoxic effect and also ameliorated the AGE mediated inflammatory reaction on human chondrocytes. Treatment of RT inhibited the levels of COX-2 and iNOS in AGE exposed chondrocytes. RT decreased the AGE mediated up-regulation of IL-6, NO, TNF-α and PGE-2 in a dose dependent manner. Pretreatment of RT decreased the extracellular matrix degradation, inhibited expression of TRAF-6 and BCL-2 the NF-κB/MAPK pathway proteins. The treatment of RT in mice prevented the calcification of cartilage tissues, loss of proteoglycans and also halted the narrowing of joint space is mice subjected to osteoarthritis. Theanalysis suggested potential binding affinity of RT with TRAF-6 and BCL-2.
CONCLUSION: In brief RT inhibited AGE-induced inflammatory reaction and also degradation of ECM via targeting the NF-κB/MAPK pathway proteins BCL-2 and TRAF-6. RT can be a potential molecule in treating OA.