A comprehensive review of natural product-derived compounds acting on P2X7R: The promising therapeutic drugs in disorders

The P2 × 7 receptor (P2 × 7R) is known to play a significant role in regulating various pathological processes associated with immune regulation, neuroprotection, and inflammatory responses. It has emerged as a potential target for the treatment of diseases. In addition to chemically synthesized small molecule compounds, natural products have gained attention as an important source for discovering compounds that act on the P2 × 7R. To explore the research progress made in the field of natural product-derived compounds that act on the P2 × 7R. The methods employed in this review involved conducting a thorough search of databases, include PubMed, Web of Science and WIKTROP, to identify studies on natural product-derived compounds that interact with P2 × 7R. The selected studies were then analyzed to categorize the compounds based on their action on the receptor and to evaluate their therapeutic applications, chemical properties, and pharmacological actions. The natural product-derived compounds acting on P2 × 7R can be classified into three categories: P2 × 7R antagonists, compounds inhibiting P2 × 7R expression, and compounds regulating the signaling pathway associated with P2 × 7R. Moreover, highlight the therapeutic applications, chemical properties and pharmacological actions of these compounds, and indicate areas that require further in-depth study. Finally, discuss the challenges of the natural products-derived compounds exploration, although utilizing compounds from natural products for new drug research offers unique advantages, problems related to solubility, content, and extraction processes still exist. The detailed information in this review will facilitate further development of P2 × 7R antagonists and potential therapeutic strategies for P2 × 7R-associated disorders.