Curcumin-Loaded Liposomes (hPLipo/Cur) with Liver-Targeting Properties for Efficient NAFLD Treatment by Alleviating Mitochondrial ROS-Mediated Ferroptosis via NRF2 Pathway.
Wang Xue, Fang Rui, Zhao Tianming, Ding Ling, Cai Mengxi, Zhang Dongbo, Xu Nuo, Yang Suzhen, Zhao Si, Zhang Han, Xie Xiaolin, Zhang Zhiheng, Zhang Ming, Zhang Li, Zhuge Yuzheng, Xu Bing
Abstract
NAFLD is a rising health problem worldwide with unsatisfied therapies. Curcumin has an ameliorative but limited effect on NAFLD due to its low water solubility. In this study, we innovatively establish the high-PC-content liposome-loaded curcumin (hPLipo/Cur) with liver-targeting properties for NAFLD therapy. hPLipo/Cur, composed of DSPC, cholesterol, and DSPE-PEG2000, has better biocompatibility and water solubility and is loaded with curcumin with high efficiency. hPLipo/Cur is superior to curcumin in improving hepatic histology, as evidenced by reducing lipid deposition and macrophage infiltration in steatohepatitis. Mechanistically, hPLipo/Cur reduces NRF2 degradation and promotes the nuclear translocation of NRF2, as well as the expression of downstream antioxidant genes. The activated NRF2 pathway reduces cellular oxidative stress and the generation of mitochondrial ROS, thereby reducing the accumulation of lipid peroxides and inhibiting ferroptosis in steatohepatitis. In conclusion, hPLipo/Cur reduces mitochondrial ROS-mediated ferroptosis by enhancing the NRF2 pathway to alleviate steatohepatitis, providing a promising strategy for NAFLD treatment.
Key Findings
- Curcumin-loaded high-PC-content liposomes (hPLipo/Cur) improve liver targeting and water solubility for NAFLD treatment.
- hPLipo/Cur reduces NRF2 degradation and promotes its nuclear translocation, activating downstream antioxidant genes.
- Activation of the NRF2 pathway by hPLipo/Cur decreases mitochondrial ROS, lipid peroxides, and inhibits ferroptosis in steatohepatitis.
Clinical Significance
hPLipo/Cur offers a promising therapeutic strategy for NAFLD by alleviating mitochondrial ROS-mediated ferroptosis through enhancement of the NRF2 antioxidant pathway, potentially improving treatment outcomes for patients with steatohepatitis.
Citation
Wang Xue, Fang Rui, Zhao Tianminget al.. Curcumin-Loaded Liposomes (hPLipo/Cur) with Liver-Targeting Properties for Efficient NAFLD Treatment by Alleviating Mitochondrial ROS-Mediated Ferroptosis via NRF2 Pathway. Molecular pharmaceutics. 2026-Apr-06.