Aescin and rutin mitigate hyperthyroidism-induced multisystem dysfunction via antioxidant and anti-inflammatory mechanisms in a rat model

Hyperthyroidism triggers systemic complications, including oxidative stress, dyslipidemia, hepatic injury, insulin resistance, and cardiovascular dysfunction. Conventional treatments such as Propylthiouracil (PTU) often exhibit adverse effects, highlighting the need for safer alternatives. We evaluated the therapeutic efficacy of the natural bioactives aescin and rutin, alone and in combination with PTU, in L-thyroxine–induced hyperthyroid rats. Comprehensive analyses included thyroid hormone levels, metabolic and hepatic biomarkers, oxidative stress indices, and histopathological/immunohistochemical evaluations of liver, heart, and pancreas. Both compounds significantly restored thyroid function by reducing FT3 and FT4 and normalizing TSH levels. Treatments improved lipid and glucose profiles, attenuated hepatic enzyme leakage, reduced proinflammatory cytokines (IL-6, TNF-α), and enhanced antioxidant defense (↑TAC, ↓MDA). Histopathology and immunohistochemistry indicated structural recovery and reduced apoptosis/oxidative stress. Aescin, particularly in combination with PTU, demonstrated superior efficacy compared to rutin or PTU monotherapy. Aescin and rutin exhibit strong antithyroid, antioxidant, hepatoprotective, cardioprotective, and neuroprotective effects. These phytocompounds may serve as potential adjuncts or alternatives to conventional antithyroid drugs, with potential translational implications for hyperthyroidism management.