Modulatory effects of Hibiscus sabdariffa extract on insulin receptor sensitivity, oxidative stress, inflammatory markers, and glucose homeostasis in a rat model of metabolic syndrome

Abstract Background The prevalence of metabolic syndrome (MS) continues to rise globally, fueled by sedentary lifestyles, poor dietary habits, and increasing rates of obesity. The underlying pathophysiology of MS involves a multifaceted interplay of insulin resistance, chronic inflammation, oxidative stress, and impaired glucose metabolism. Natural products such as are emerging as promising alternatives for MS management, offering potential therapeutic benefits with fewer side effects. This study investigates the therapeutic potential of HS extract in alleviating features of metabolic syndrome. Methods Thirty-five male rats were randomly divided into five groups (n = 7 per group). The control group received distilled water, while the negative control group was administered 20% fructose without treatment. The remaining three groups received daily doses of HS extract along with 20% fructose for eight weeks. Results Biochemical analyses of blood and pancreatic tissues revealed that HS significantly ( p < 0.05) mitigated oxidative stress by reducing lipid peroxidation and enhancing endogenous antioxidant activity. HS treatment also led to significant downregulation of pancreatic AKR1B1, GSK-3, TNF-α, and INF-γ ( p < 0.05). Furthermore, the HS-treated groups exhibited reduced serum insulin levels, lower HOMA-IR and HOMA-β indices, and improved insulin sensitivity as indicated by QUICKI ( p < 0.05). Oral glucose tolerance was enhanced in HS-treated rats, with a decreased area under the curve. Notably, blood glucose and free fatty acid levels were significantly lowered ( p < 0.05). Conclusion These findings show the potential of Hibiscus sabdariffa extract as a natural intervention for managing metabolic syndrome. Graphical Abstract