Emerging roles of combined curcumin and berberine in disease modulation: a comprehensive review of mechanisms and therapeutic relevance.

Curcumin, a polyphenolic compound derived from Curcuma longa, and berberine, an isoquinoline alkaloid extracted from plants such as Coptis chinensis, exhibit multifaceted pharmacological properties, including potent antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. This narrative review evaluates their therapeutic potential across a diverse range of conditions, including nonalcoholic fatty liver disease (NAFLD), various malignancies, wound and plant infections, Alzheimer's disease, cardiovascular disorders, irritable bowel syndrome, cyclophosphamide-induced toxicity, interstitial cystitis, and systemic lupus erythematosus. Mechanistically, curcumin and berberine modulate gut microbiota, suppress lipogenic and inflammatory pathways (e.g., SREBP-1c and NF-κB), and activate PI3K/Akt and PPARγ signaling, thereby reducing hepatic steatosis and inflammation. Furthermore, they induce apoptosis, inhibit the PI3K/Akt/mTOR pathway, and modulate the tumor microenvironment, with their enhanced combined effects being significantly amplified by nanodelivery systems, such as liposomes. Their antimicrobial efficacy targets methicillin-resistant Staphylococcus aureus (MRSA) and plant pathogens by disrupting biofilms and generating reactive oxygen species via nanofibers and self-assembled submicron particles. Moreover, they reduce amyloid-beta aggregation, promote autophagy, and mitigate neuroinflammation. Additionally, their immunomodulatory properties effectively suppress autoimmune responses. Ultimately, this review synthesizes the current evidence regarding the therapeutic versatility of curcumin and berberine across multiple pathologies.