article · Journal of Ethnopharmacology
Traditional medical systems offer valuable insights for identifying new anti-inflammatory treatments. This research evaluates evidence on how natural products from traditional medicines affect the Receptor for Advanced Glycation End-products, known as RAGE. By examining literature on molecular pharmacology, the findings highlight that natural compounds such as polyphenols, terpenoids, and alkaloids can target the RAGE pathway at multiple points. Specifically, they can inhibit the formation of advanced glycation end-products, block receptor binding, reduce receptor expression, and suppress subsequent inflammatory signalling. Specific compounds, including quercetin, ursolic acid, and berberine, demonstrate notable activity across preclinical models. While obstacles regarding bioavailability and translation to clinical settings persist, these plant-derived substances provide a promising multi-target alternative to conventional single-target synthetic drugs for managing chronic inflammatory diseases.
Chronic inflammatory diseases place a significant burden on global health. Synthetic drugs typically focus on single targets, which can limit their effectiveness. Understanding how traditional natural remedies disrupt inflammation at several biological points offers a pathway toward more versatile treatments, helping scientists combine historical indigenous medicine with modern pharmaceutical science to address complex inflammatory conditions.
The findings point towards applications in pharmaceutical development for chronic inflammatory disorders. Drug developers and formulation scientists could use these natural lead compounds to design multi-target therapies. However, commercial application is at an early stage, as evidence is currently confined to preclinical models. Developing practical therapies will require overcoming explicit hurdles in compound bioavailability and navigating the pathway to clinical translation.
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ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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DOI: 10.1016/j.jep.2026.122144
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