Icariin attenuates oxidative stress via SIRT1/PGC-1α pathway in SAH mice

Oxidative stress plays a pivotal role in the pathological response of subarachnoid hemorrhage (SAH). Icariin (ICA), with its potent antioxidant properties, exerts neuroprotective effects in stroke. This study investigated the beneficial effects of ICA on SAH-induced oxidative damage and its possible molecular mechanisms. The results indicated that ICA treatment improved both short-term and long-term neurobehavioral functions in mice with SAH. ICA significantly inhibited SAH-induced Reactive Oxygen Species (ROS) generation and lipid peroxidation. Simultaneously, ICA restored the activity of the endogenous antioxidant enzyme system. Furthermore, ICA mitigated mitochondrial damage, improved mitochondrial morphology, further reduced neuronal Apoptosis, and decreased brain edema following SAH. Mechanistically, ICA suppressed oxidative stress after SAH by activating Sirtuin 1 (SIRT1), subsequently upregulating the expression of PGC-1α. The SIRT1 Inhibitor EX527 significantly inhibited ICA-induced SIRT1 activation and abolished the antioxidant and neuroprotective effects of ICA. In cellular experiments, ICA also inhibited ROS production and enhanced cell viability. These effects were associated with SIRT1 activation and were reversed by EX527 treatment. In conclusion, this study explored the protective effects of ICA against SAH-induced oxidative damage, suggesting that ICA could be a potential therapeutic agent for SAH.

Icariin; Neuronal apoptosis; Oxidative stress; Sirtuin 1; Subarachnoid hemorrhage.