Advances and Perspectives in Curcumin Regulation of Systemic Metabolism: A Focus on Multi-Organ Mechanisms.

Curcumin, a natural polyphenol derived from turmeric, functions as a potent exogenous antioxidant and exhibits a range of benefits in the prevention and management of metabolic diseases. Despite its extremely low systemic bioavailability, curcumin demonstrates significant bioactivity in vivo, a phenomenon likely attributable to its accumulation in the intestines and subsequent modulation of systemic oxidative stress and inflammation. This article systematically reviews the comprehensive regulatory effects of curcumin on systemic metabolic networks-including glucose metabolism, amino acid metabolism, lipid metabolism, and mitochondrial metabolism-and explores their molecular basis, particularly how curcumin facilitates systemic metabolic improvements by alleviating oxidative stress and interacting with inflammation. Preclinical studies indicate that curcumin accumulates in the intestines, where it remodels the microbiota through prebiotic effects, enhances barrier integrity, and reduces endotoxin influx-all of which are critical drivers of systemic oxidative stress and inflammation. Consequently, curcumin improves insulin resistance, hyperglycemia, and dyslipidemia across multiple organs (liver, muscle, adipose) by activating antioxidant defense systems (e.g., Nrf2), enhancing mitochondrial respiratory function (via PGC-1α/AMPK), and suppressing pro-inflammatory pathways (e.g., NF-κB). Clinical trials have corroborated these effects, demonstrating that curcumin supplementation significantly enhances glycemic control, lipid profiles, adipokine levels, and markers of oxidative stress and inflammation in patients with obesity, type 2 diabetes, and non-alcoholic fatty liver disease. Therefore, curcumin emerges as a promising multi-target therapeutic agent against metabolic diseases through its systemic antioxidant and anti-inflammatory networks. Future research should prioritize addressing its bioavailability limitations and validating its efficacy through large-scale trials to translate this natural antioxidant into a precision medicine strategy for metabolic disorders.