The modulation of RAGE by natural products and traditional medicines: Opening promising perspectives for inflammatory diseases.

Traditional and indigenous medical systems have a long history of using medicinal plants to treat conditions now understood as chronic inflammation. This ethnopharmacological knowledge provides a rich resource for discovering novel anti-inflammatory agents. This review critically evaluates the evidence for the modulation of the Receptor for Advanced Glycation End-products (RAGE) signaling pathway by natural products derived from traditional medicines, aiming to connect this traditional knowledge with modern molecular pharmacology. A comprehensive literature review was performed using the PubMed database. The search focused on keywords such as "RAGE," "natural products," and "traditional medicine" to identify studies detailing the mechanistic interactions between natural compounds and the RAGE pathway. Natural products, including polyphenols, terpenoids, and alkaloids, modulate the RAGE axis through several key mechanisms: (1) inhibiting the formation of Advanced Glycation End-products (AGEs); (2) directly blocking the RAGE-ligand interaction; (3) downregulating RAGE expression; and (4) suppressing downstream inflammatory signaling. Compounds like quercetin, ursolic acid, and berberine have demonstrated significant activity in various preclinical models. Natural products represent a profound source of multi-target RAGE modulators, offering a potential therapeutic advantage over synthetic single-target drugs. While challenges in bioavailability and clinical translation remain, the data strongly validates the ethnopharmacological approach. Future progress depends on integrating this traditional wisdom with modern technologies to unlock the full clinical potential of these compounds.