Targeting of Nrf2/PPARγ/NLRP3 Signaling Pathway by Stevia rebudiana Bertoni Extract Provides a Novel Insight into Its Protective Effect against Acute Gouty Arthritis-Induced Synovial Inflammation, Oxidative Stress and Apoptosis in a Rat Model

• Published in: Processes 2022-09, Vol.10 (9), p.1751
• Main Authors: Badawy, Alaa M., Taha, Medhat, Elazab, Sara T., El-Shenbaby, Ibrahim, Alghamdi, Bandar A, M, Hendawy, Al-Kushi, Abdullah G., Fathy, Khaled, Baokbah, Tourki A. S., Ibrahim, Mohie Mahmoud
• Format: Article
• Language: English
• Subjects: Ankle; Apoptosis; Arthritis; Bax protein; Bcl-2 protein; Caspase-3; Colchicine; Crystals; Cytochrome c; Cytochromes; Drug dosages; Edema; Enzymes; Experiments; Gene expression; IL-1β; Inflammation; Interleukin 18; Laboratory animals; Medical research; NF-κB protein; Nitric oxide; Oxidative stress; Peroxisome proliferator-activated receptors; Pretreatment; Proteins; Signal transduction; Stevia; Tumor necrosis factor-α; Uric acid
• ISSN: 2227-9717; 2227-9717
• DOI: 10.3390/pr10091751

Our research work examined the potential protection of Stevia rebaudiana extract against monosodium urate crystals (MSU)-induced acute gouty arthritis in a rat model and its possible underlying mechanism. Forty rats were allocated into four groups (n = 10); a control group; an MSU group, whose rats received 0.1 of MSU single intra-articular injection in the ankle joint on the fifth day of the experiment; an MSU + Stevia group, which received 250 mg/kg/day of Stevia extract orally for seven days and MSU crystals on the fifth day; and an MSU + colchicine group, which was administered colchicine at 0.28 mg/kg daily for seven days and MSU crystals on the fifth day. Pretreatment with Stevia extract mitigated MSU-induced inflammation as evidenced by a decrease of the ankle edema and inflammatory cell infiltration and a significant downregulation of the protein level of NFκB, TNFα, IL-1β, IL6, and IL18 as well as NLRP3 gene expression. Additionally, there was a markedly increased PPARγ gene expression (p < 0.001) compared with the MSU group (p < 0.001) and alleviated oxidative stress via significant upregulating of Nrf2/HO-1. Moreover, the pretreatment attenuated apoptosis by significantly decreasing cytochrome c, Bax, Caspase-3, and by increasing Bcl-2 protein. In conclusion, Stevia extract exhibited strong anti-inflammatory, antioxidant, and antiapoptotic effects against MSU-induced gouty arthritis similar to the standard anti-inflammatory colchicine drugs.