Network Pharmacology Analysis and Experimental Validation of Tectoridin in the Treatment of Ischemic Stroke by Inhibiting Apoptosis and Regulating Inflammation

The flowers of <i>Pueraria lobate</i> (Puerariae Flos) have served as a traditional Chinese medicinal and food herbage plant for many years. Tectoridin is one of the most active metabolites extracted from flowers of <i>Pueraria lobate</i> and has a variety of beneficial activities, including antioxidative, hypoglycemic, and anti-inflammatory activities. Nevertheless, the functions and potential mechanisms underlying tectoridin in cerebral ischemia/reperfusion injury have not been well interpreted; thus, a network analysis strategy was performed to systematically evaluate its pharmacological mechanisms, which were further validated in rats with cerebral ischemia. Network analysis predicted that tectoridin could attenuate brain damage after stroke by modulating signaling pathways associated with redox, inflammation, and autophagy. The experimental results demonstrated an improvement in neurological function in rats treated with tectoridin, along with a significant reduction in cerebral infarction volume. The neuroprotective benefits of tectoridin stem, in part, from its antioxidant capabilities, which include the upregulation of Nrf2/HO-1 protein expression, reduction of the TLR4/MYD88/NF-κB inflammatory pathway, and inhibition of the PI3K/Akt/mTOR pathway, contributing to its anti-apoptotic effects. This investigation offers a thorough examination of the pathways and targets linked to the therapeutic effects of tectoridin on ischemic stroke, highlighting its anti-inflammatory, antioxidative, and anti-apoptotic mechanisms. These findings serve as a valuable reference for the development and exploration of effective anti-ischemic stroke medications.