Curcumin Metabolites and Metabolic Health: Insights into Regulatory Mechanisms of Glucose and Lipid Homeostasis.

Curcumin, a bioactive compound and vibrant yellow pigment extracted from the rhizome of Curcuma longa, has a well-established safety profile and demonstrates defined pharmacological activities. These activities include regulating glucose and lipid metabolism, exerting anti-oxidant effects, and modulating autophagy. However, its pharmacokinetic limitations-notably low oral bioavailability and insufficient blood concentration-present a dichotomy with its significant biological effects. Research indicates that curcumin undergoes rapid and extensive metabolic transformation in vivo, which suggests that its pharmacological actions may be partially mediated by metabolites. Notably, curcumin metabolites exhibit activity comparable to, or even exceeding, the therapeutic potential of the parent compound in models of glucose and lipid metabolism disorders. Through a systematic review of curcumin's metabolic pathways and the targets of its metabolites, we identified several key conclusions. First, the beneficial effects of curcumin on glucose and lipid metabolism are closely linked to its reduced metabolites dihydrocurcumin, tetrahydrocurcumin, and hexahydrocurcumin. Second, the parent compound curcumin and its metabolites exhibit overlapping actions on core signaling pathways, such as PPARα, NF-κB, and PI3K-AKT, which confirms metabolites as significant contributors to the overall efficacy. Third, preclinical research focusing on these reduced metabolites offers promising new directions for combination therapies targeting glucose and lipid metabolism disorders and their complications. Building upon these conclusions, this paper further synthesizes the structure-activity relationships of the principal reduced metabolite-tetrahydrocurcumin, which is characterized by its high abundance among metabolites and concentrated research focus on its modification, and aims to provide a theoretical foundation for structure optimization and drug development based on metabolites.