49-PUB: Targeting Hepatic Oxidative Stress in Diabetes: Antioxidant and Cytoprotective Effects of Hypericum perforatum L. Aerial and Hairy Root Methanolic Extracts

Introduction and Objective: Diabetes mellitus is associated with pronounced hepatic oxidative stress caused by excessive reactive oxygen species production, impaired antioxidant defenses, and activation of stress-responsive signaling pathways. Building on evidence of the antidiabetic potential of Hypericum perforatum L. aerial parts (Hyperici herba, HH) and H. perforatum hairy root (HR) extracts, this study aimed to evaluate their effects on hepatic oxidative stress and cytoprotective responses in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of STZ (45 mg/kg), followed by oral treatment for 14 days with HH or HR extracts (200 mg/kg), glibenclamide (2.5 mg/kg), or vehicle (0.3% carboxymethylcellulose). Hepatic redox status was assessed by measuring enzymatic and non-enzymatic antioxidant defenses, lipid peroxidation, Cyp2e1 expression, PARP activity, and HSP70 levels. Results: Diabetic rats exhibited severe oxidative damage and compromised cellular defense mechanisms, evidenced by glutathione depletion, reduced ferric reducing antioxidant power, decreased catalase, superoxide dismutase, and glutathione peroxidase activities, along with enhanced lipid peroxidation, Cyp2e1 expression, and PARP activation. Treatment with HH and HR extracts significantly restored antioxidant capacity, suppressed lipid peroxidation, and attenuated Cyp2e1 and PARP activation, whereas such effects were limited in glibenclamide-treated animals. HH extract additionally increased hepatic HSP70 levels in diabetic rats, suggesting improved cellular stress adaptation, while both extracts reduced basal HSP70 levels in healthy animals. Conclusion: Overall, HH and HR extracts exert significant hepatoprotective effects by modulating multiple oxidative stress pathways independently of glycemic control, supporting their potential as adjunct strategies for preventing diabetes-associated liver injury. Disclosure E. Rafailovska: None. E. Mirova: None. O. Tusevski: None. R. Stojchevski: None. D. Avtanski: None. S. Gadzovska-Simic: None. S. Dinevska Kjovkarovska: None. B. Miova: None.