A comprehensive compendium of berberine: sources, chemistry, and pharmacological activities.

Berberine, an isoquinoline alkaloid that is naturally derived from Berberis species, owing to its broad spectrum of pharmacological activities, has been of significant interest due to its high potency for the treatment of metabolic, cardiovascular, neurological, and inflammatory diseases by modulation of cellular signaling pathways, antimicrobial action, and cytoprotection. Its therapeutic use, however, is still marred by poor oral bioavailability. This review aims to assess the therapeutic potential of berberine, highlight its pharmacological and structural characteristics, and discuss formulation advancements that optimize its bioavailability, with specific focus on its application in the control of chronic disease. Recent developments in structure-activity relationships, particularly at positions carbon-8 and carbon-13, are discussed in addition to nanocarrier drug delivery systems (such as phytosomes, nanoemulsions, solid dispersions, and inclusion complexes). Analytical methods and information from randomized controlled trials were also taken into account for compound isolation/quantification and therapeutic activity, respectively. The findings demonstrate that improved berberine drug formulations have better absorption, stability, and extended pharmacologic effects, supported by clinical evidence confirming its application in the management of type 2 diabetes, polycystic ovary syndrome, non-alcoholic fatty liver disease, and hyperlipidemia. In summary, berberine offers an exciting, multipurpose drug, and further formulation innovation and more rigorous clinical establishment are required to realize its benefits as broad biomedical and nutritional applications. © 2025 Society of Chemical Industry.