Role of mitochondrial metabolism in ischemic stroke and natural products intervention

Within minutes of an ischemic stroke, mitochondrial dysfunction and energy metabolism disorders occur. This leads to a sustained release of glutamate and an overload of intracellular calcium. An increase in intracellular Ca²⁺ leads to an excessive production of ROS, which in turn activates inflammatory responses. IR leads to the succinate metabolism, which causes an imbalance in the redox state. This imbalance can trigger a series of cascade reactions that may lead to the death of damaged neurons and the leakage of the blood-brain barrier. During IR, the disruption of key enzymes and metabolic intermediates is crucial in exacerbating mitochondrial dysfunction. Mitochondrial dysfunction in ischemic stroke involves a complex network of metabolic pathways, including glutamate metabolism, succinate metabolism, and fatty acid metabolism. This complexity lays the groundwork for creating new therapeutic strategies. Several natural products, such as EGb761, tanshinones, and notoginsenosides, have shown promising effects in regulating mitochondrial metabolism, which has the potential to restore energy production, thereby alleviating oxidative stress. This review systematically summarized the multi-target mechanisms of ischemic stroke from the aspect of mitochondrial metabolism. And the clinical applications of natural products against ischemic stroke were also reviewed. Future research should aim to clarify how natural products can treat ischemic stroke by influencing mitochondrial pathways.