Rhoifolin regulates oxidative stress and proinflammatory cytokine levels in Freund’s adjuvant-induced rheumatoid arthritis via inhibition of NF-κB

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease of knee joints involving pain and inflammation. Rhoifolin is a plant flavonoid known to have antioxidant and anti-inflammatory properties. This study was taken to identify the effect of rhoifolin on complete Freund's adjuvant (CFA)-induced arthritis in the rat model. Treatment with rhoifolin (10 and 20 mg/kg) showed a significant improvement in the overall health parameters such as paw edema and weight loss. This improvement in morphological parameters corroborated the findings with gross morphological changes observed in the histopathological analysis. Rhoifolin treatment also caused a significant decrease in oxidative stress, evident from changes in intracellular levels of glutathione, glutathione peroxidase, malondialdehyde, and superoxide dismutase in the articular cartilage tissue. Moreover, proinflammatory cytokines, tumor necrosis factor (TNF)-a, interleukin(IL)-1b, and IL-6 showed a significant downregulation of gene expression and intracellular protein concentration levels. The NF-kB pathway showed a significant attenuation as evident in the significant reduction in the levels of NF-kB p65 and p-IkB-a. These results indicated that rhoifolin can be a natural therapeutic alternative to the extant regimens, which include non-steroidal anti-inflammatory drugs and immunosuppressants. Additionally, the antioxidant and anti-inflammatory action of rhoifolin was probably mediated by the NF-kB pathway. However, the exact target molecules of this pathway need to be determined in further studies.

Ameliorative Effects of Rhoifolin in Scopolamine-Induced Amnesic Zebrafish (Danio rerio) Model

“…While microglial activation is a resident innate immune protection in the central nervous system [ 48 ], over-activation of microglial cells can trigger inflammatory reactions that produce neurotoxic compounds, including nitric oxide (NO), prostaglandin E 2 (PGE 2 ), and tumor necrosis factor-α (TNF-α) [ 49 ]. Besides, it has been shown that Rho regulated oxidative stress and proinflammatory cytokine levels in Freund’s adjuvant-induced rheumatoid arthritis by inhibition of the NF-κB pathway [ 50 ]. As expected in this study, the administration of Sco significantly increased levels of protein carbonyl and lipid peroxidation (MDA), suggesting the induction of oxidative stress in the zebrafish brain.…”

Rhoifolin Ameliorates Osteoarthritis via Regulating Autophagy

“…In recent years, natural plant extract has attracted wide attention in OA therapy for its potential anti-inflammatory properties and mild side effects (Dragos et al, 2017). Rhoifolin (ROF), a flavanone first extracted from Rhus succedanea, has showed its anti-inflammatory potential in lipopolysaccharideinduced acute inflammation (Fang et al, 2020), Freund's adjuvant-induced rheumatoid arthritis (Peng et al, 2020), and agerelated inflammation (Lim et al, 2017). In this study, for the first time, we report the therapeutic effects of ROF in rat OA as well as the underlying mechanisms.…”

“…Due to mild side effects and definite efficacy, more and more herb medicines have been accepted by OA patients (Li et al, 2017). Rhoifolin, a bioactive product first extracted from Rhus succedanea, has proved its anti-oxidative and antiinflammatory properties in several diseases (Fang et al, 2020;Gandhi et al, 2020;Peng et al, 2020). In vitro, ROF attenuated osteoclasts-stimulated ostolysis via suppressing MAPK and NFκB signal pathways, indicating the possible mechanism of its action (Liao et al, 2019).…”

β-Selective Glycosylation Using Axial-Rich and 2-<i>O</i>-Rhamnosylated Glucosyl Donors Controlled by the Protecting Pattern of the Second Sugar

“…2-O-α-L-Rhamnosyl-D-glucose (neohesperidose) is a common disaccharide present in plants, and it frequently forms β-glycosyl bonds with an aglycon, such as naringin or neohesperidin 1,2) (Fig. 1a).…”