The role of gasdermin D-mediated pyroptosis in hepatic ischemia-reperfusion injury and prediction of the therapeutic natural products.

Hepatic ischemia-reperfusion injury (HIRI) represents a frequent and unavoidable complication following liver resection or liver transplantation, which can profoundly impair hepatic function and even cause irreversible tissue damage, precipitating multiple organ dysfunction and ultimately adversely influencing both the prognosis and overall patient survival. Inflammation demonstrates a robust association with HIRI and serves a crucial function across the entire pathological course of HIRI. In this context, pyroptosis constitutes a controlled inflammatory cell death mechanism that contributes substantially to the pathological progression of HIRI. Throughout HIRI development, gasdermin D (GSDMD) functions as the primary effector following caspase 1 activation. This review provides a concise summary and emphasizes the intricate cellular and molecular mechanisms underlying GSDMD-mediated pyroptosis, particularly focusing on its involvement in HIRI. Meanwhile, the potential therapeutic effect of the natural products that act on GSDMD was predicted, which would broaden the treatment options available for HIRI. However, existing research remains confined to laboratory-based investigations and lacks clinical studies to advance a comprehensive understanding of GSDMD-induced pyroptosis in the occurrence and progression of HIRI. Therefore, enhanced comprehension of GSDMD mechanisms and the development of GSDMD-targeting inhibitors may offer promising clinical application prospects for managing HIRI.