The role of natural polyphenols in purinergic signaling: from molecular mechanisms to physiological implications.

Purinergic signaling plays a pivotal role in regulating cellular functions involved in many pathogenic processes underlying the development of cardiovascular, neurological, and malignant disorders. Therefore, identifying novel, safe, and efficient inhibitors to regulate the actions of extracellular purines and pyrimidines via their wide array of P1 and P2 membrane receptors is crucial for better management of these diseases in the future. In recent years, numerous studies have demonstrated that natural polyphenolic compounds derived from various plant extracts can modulate purinergic receptor activity and thereby regulate downstream intracellular signaling pathways. In this review article, the current knowledge of these activities is compiled to provide a useful platform for advancing natural lead compounds as novel inhibitors of purinergic signaling.