Rosuvastatin Attenuates Rheumatoid Arthritis-Associated Manifestations via Modulation of the Pro- and Anti-inflammatory Cytokine Network: A Combination of In Vitro and In Vivo Studies

Abstract

The current investigation employed rosuvastatin for evaluation as an antiarthritic agent by in vitro and in vivo studies. In vitro studies comprised egg albumin and bovine serum albumin protein denaturation assays along with membrane stabilization assays, while in vivo studies comprised formaldehyde and complete Freund’s adjuvant (CFA)-provoked arthritis. The antioxidant potential was estimated via DPPH free radical scavenging and ferric reducing assays. Rosuvastatin significantly inhibited heat-provoked protein denaturation of egg albumin and bovine serum in a concentration-dependent way with the highest inhibition of 1225 ± 9.83 and 82.80 ± 4.03 at 6400 μg/mL. The percentage protection of the RBC membrane from hypotonicity-prompted lysis was found to be 80.67 ± 2.7. Rosuvastatin promisingly subdued formaldehyde-provoked arthritis, with maximum reduction (65.47%) of the paw volume being observed at a dose of 40 mg/kg. Rosuvastatin also significantly (p < 0.001) attenuated arthritis induced by CFA injection by reducing the paw volume and arthritic index. The reduction in the body weight due to CFA injection was also preserved by rosuvastatin treatment. Hematological and biochemical changes due to arthritis induction by CFA injection were also maintained near normal values by rosuvastatin. The histopathological and radiographic investigation also revealed the protective effect of rosuvastatin on preventing structural changes. Gene expression of IL-1β, TNF-α, and IL-6 was reduced, while IL-4 and IL-10 levels were elevated by rosuvastatin in comparison to those for the disease control group. Concentration-dependent antioxidant potential was shown by rosuvastatin. Thus, rosuvastatin possesses a notable antiarthritic potential as evidenced via in vitro and in vivo studies.

Rosuvastatin Induces Renal HO-1 Activity and Expression Levels as a Main Protective Mechanism against STZ-Induced Diabetic Nephropathy

“…In the present study, the DN group also showed high expression of renal TNF-α, signifying the stimulation of inflammatory pathway and cytokine production, which was ameliorated by RSV administration. This is in line with the reported anti-inflammatory effect of RSV decreasing TNF-α in diabetic nephropathy [ 45 ], LPS-induced cardiac injury [ 46 ] and rheumatoid arthritis animal models [ 47 ]. Apoptosis in renal tissue, in the current study, was also seen after the induction of DN, as indicated by increased renal expression of the pro-apoptotic protein, caspase 3, which was reversed by RSV administration.…”

Zerumbone Protects Rats from Collagen-Induced Arthritis by Inhibiting Oxidative Outbursts and Inflammatory Cytokine Levels

“…In the onset of RA, genetic composition and smoking are the predominant risk factors, and RA is diagnosed by clinical and laboratory assessments. In the diagnosis of RA, a combination of autoantibodies, i.e., rheumatoid factors (RF), anticitrullinated protein/peptide antibody (ACPA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and X-ray imaging are frequently used. − Research studies have reported that inflamed synovial fibroblasts play a major role in RA pathogenesis by stimulating the synthesis of proinflammatory mediator molecules. − Mitogen-activated protein kinases (MAPK) and nuclear factor-κB are the main proinflammatory signalling pathways that mediate the expression of inflammatory molecules …”

“…8−10 Mitogen-activated protein kinases (MAPK) and nuclear factor-κB are the main proinflammatory signalling pathways that mediate the expression of inflammatory molecules. 11 Collagen-induced arthritis (CIA) is an excellent model for RA as it has helped to know and reveal pathogenic perspectives of autoimmune disease. It is critical to know about the distinct types of cells and their roles in the development of CIA and to test and develop novel therapeutic approaches.…”

“… 8 − 10 Mitogen-activated protein kinases (MAPK) and nuclear factor-κB are the main proinflammatory signalling pathways that mediate the expression of inflammatory molecules. 11 …”

Pterostilbene exert an anti‐arthritic effect by attenuating inflammation, oxidative stress, and alteration of gut microbiota

“…The discovery of novel biologics such as tofacitinib, infliximab, sarilumab, rituximab, and tocilizumab as a result of the comprehensive genetic analysis of RA disease has led to the development of more effective treatments. These medications have the ability to interfere with immune system components that are primarily responsible for tissue and joint inflammation (Kumar, Dhaliwal, et al., 2020; Qasim et al, 2021). But few reports showed that patients who received the above treatment were more prone to soft tissue, skin, respiratory, joint/bone, and genitourinary infections as compared with the herbal drugs.…”