Evaluation of the antirheumatic effects of isoflavone-free soy protein isolate and etanercept in rats with adjuvant-induced arthritis

Abstract

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by persistent synovitis, autoantibodies, and systemic inflammation. This study evaluates the possible antirheumatic effect of isoflavone-free soy protein isolate (SPI) in adjuvant-induced arthritis in rats. Male albino rats were divided into four groups: the control, arthritis, SPI, and etanercept (ETN) groups. Arthritis was induced by a single subcutaneous injection of 0.1 mL of complete Freund’s adjuvant. Treatment with 4 g/kg SPI orally every day or 3 mg/kg ETN subcutaneously three times/week started on the day of arthritis induction. After 11, 21, or 31 days, the rats were sacrificed, serum was collected for analysis of different biological markers, and the right ankle of each animal was obtained for histopathological examination. Serum levels of anticyclic citrullinated peptide (anti-CCP) antibodies, tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), malondialdehyde (MDA), and hypercholesterolemia gradually increased in the arthritis animals compared to the control animals. Compared to the arthritis group, the ETN group showed significantly reduced anti-CCP levels at each of the three experimental periods, while a significant reduction in TNF-α, MMP-3, and MDA levels was observed after 21 and 31 days. ETN had no significant effect on the lipid profile after the three experimental periods. SPI significantly reduced anti-CCP, TNF-α, and MMP-3 levels after 31 days. The hypocholesterolemic effect of SPI and a significant reduction in MDA levels were observed after 21 and 31 days. Both ETN and SPI reduced the severity of arthritis-induced histopathological changes. These findings indicate that SPI has anti-inflammatory, antirheumatic, and hypocholesterolemic effects, suggesting it as a complementary therapy for RA. Impact statement In view of the partial clinical benefit and significant toxicity of traditional rheumatoid arthritis (RA) treatments, there is a growing trend to use complementary therapy. The antiarthritic activity of soy is related to the effect of soy isoflavones. However, little is known about the antiarthritic activity of soy protein itself. This study demonstrates that soy protein isolate (SPI) and etanercept (ETN), a tumor necrosis factor-α (TNF-α) inhibitor, protect rats against the effects of adjuvant-induced arthritis (AIA) by reducing inflammation (TNF-α and matrix metalloproteinase-3), autoantibody production (anticyclic citrullinated peptide), and lipid peroxidation (malondialdehyde). Only SPI improved dyslipidemia accompanied by RA, giving it the advantage of reducing cardiovascular risk. Additionally, the severity of arthritis-induced pathology, including inflammatory infiltrates, synovial hyperplasia, pannus formation, synovial vascularity, and cartilage erosions, was reduced by both SPI and ETN. This research ascertains the possible antiarthritic effect of SPI, making it a recommended alternative therapy for RA.