Anti-inflammatory effect of Quercetin and rapamycin in rat rheumatoid arthritis model by targeting PI3K/AKT/mTOR pathway

Rheumatoid arthritis (RA) is one of the most prevalent chronic autoimmune disorders that primarily affects the articular tissue and is associated with significant systemic comorbidities. While numerous disease modifying anti-rheumatic drugs (DMARDs) are available for therapy, they are still not enough for most of patients to relieve pain. In addition to having several adverse effects, patients continue to have functional decline despite the use of these drugs. Quercetin, a natural bioflavonoid known for its potent anti-inflammatory and antioxidant properties, presents a promising alternative in the treatment of RA. Thus, our study estimated the effect of quercetin in a Freund’s Adjuvant-induced rat model of RA to test the effectiveness of quercetin through suppression of the PI3K/AKT/mTOR signalling pathways. Furthermore, we compared Quercetin's effects with those of Rapamycin (an established mTOR inhibitor) to validate the pathway's involvement in RA pathogenesis. Twenty-four rats Sprague Dawley of male sex were classified into four groups: negative control, arthritic group, rapamycin treated group, quercetin treated group. At the end of the study, before scarification, assessments of all the following were done, ankle diameter, arthritic score, and gaiting score. Then, animals were scarified, and the following markers were estimated: serum rheumatoid factor (RF) and CRP, and serum IL-1β and TNF-α. mTOR was estimated by western blotting and real-time PCR. p-AKT was evaluated by western blotting. The joint tissues were stained for H&E to detect the main histopathological alterations. Quercetin and rapamycin improved ankle diameter, arthritic score, gaiting score, and decreased joint inflammation markers, as well as decreased mTOR and p-AKT expression. Histopathological examination confirmed the effects of quercetin and rapamycin as detected by light microscopy. Quercetin can modulate pathological and biochemical alternations in Freund adjuvant induced arthritis and can be considered a new possible disease modifying antirheumatic option for rheumatoid arthritis through its effect on PI3K/AKT/mTOR pathway.