Manju Ne, Anuradha Natarajan, F. Sherin Rebecca, Rajamanickam Pon Nivedha, Hemalatha R, Ponnulakshmi Rajagopal, Ramya Murali, Vishnu Priya Veeraraghavan, G. Sridevi, Chella Perumal Palanisamy, Selvaraj Jayaraman
Background: Type 2 diabetes mellitus (t2dm) is characterized by impaired insulin signaling, oxidative stress, and chronic inflammation. Aim: The present study aimed to investigate the molecular effects of seenthil polyherbal formulation (sph) on the irs-1/pi3k/akt/glut4 insulin signaling pathway and the nrf2–keap1 antioxidant system in streptozotocin (stz)- induced diabetic rats. Methods: Adult male wistar rats (n=32) were divided into four groups: control, diabetic (dm), sph-treated (500 mg/kg), and metformin-treated (50 mg/kg). Gene expression levels of insulin signaling markers (ir, irs-1, pi3k, akt, as160, glut4), antioxidant markers (nrf2, keap1), and inflammatory cytokines (il-1β, il-6, tnf-α) were analyzed using rt-pcr. Statistical significance was determined by one-way anova followed by duncan's multiple range test, with p<0.05 considered significant. Results: The diabetic group showed significant downregulation of ir, irs-1, pi3k, akt, as160, and glut4 gene expression compared to control (p<0.05), indicating impaired insulin signaling. Sph treatment significantly upregulated these genes compared to the diabetic group (p<0.05), with near-normal restoration of irs-1 and glut4 expression. Similarly, nrf2 expression was significantly decreased in diabetic rats and was markedly increased following sph treatment (p<0.05), while keap1 expression was normalized (p<0.05). Pro-inflammatory cytokines il-1β, il-6, and tnf-α were significantly elevated in the diabetic group (p<0.05), whereas sph treatment significantly reduced their expression levels (p<0.05). Metformin treatment also showed significant improvements (p<0.05), though sph exhibited relatively stronger effects on glut4 expression. Conclusion: Sph effectively ameliorates insulin resistance, oxidative stress, and inflammation by modulating key molecular pathways, suggesting its potential as a multi-target therapeutic agent for t2dm