Berberine in oral diseases: molecular mechanisms and therapeutic implications

Oral diseases, including periodontitis, oral mucosal diseases, dental caries, endodontic diseases, and oral cancer, are among the most prevalent diseases worldwide and impose substantial health and economic burdens. Current therapeutic strategies are often limited by incomplete efficacy, drug resistance, or adverse effects, highlighting the need for alternative pharmacological approaches. Berberine, a natural isoquinoline alkaloid derived from medicinal plants such as Coptis chinensis and Phellodendron species, has attracted increasing attention because of its broad pharmacological properties. Accumulating evidence indicates that berberine exerts antimicrobial, anti-inflammatory, antioxidant, bone-regulating, and antitumor effects, which are closely associated with key pathogenic mechanisms involved in oral diseases. This review systematically summarizes the pleiotropic pharmacological effects of berberine and discusses its mechanistic roles in the management of periodontitis, recurrent aphthous ulcers, oral candidiasis, dental caries, pulpitis and apical periodontitis, and oral cancer. In addition, recent advances aimed at improving the bioavailability of berberine through novel drug delivery systems, including nanocarriers and hydrogels, are summarized. Finally, current challenges and future research directions are proposed to facilitate the clinical translation of berberine-based therapies in oral diseases.