无载体水飞蓟宾/索拉非尼微粒通过调节脂肪酸代谢减轻代谢功能障碍相关脂肪性肝病

Carrier-Free Silibinin/Sorafenib Microparticles Alleviate Metabolic Dysfunction-Associated Steatotic Liver Disease by Modulating Fatty Acid Metabolism.

作者信息

Han Feifei, Wang Haiping, Wang Li, Fan Limei, Peng Sibei, Hou Xiaoying, Shu Xiji, Sun Binlian, Liu Yuchen

机构信息

Cancer Institute, School of Medicine, Jianghan University, Wuhan, Hubei, 430056, People's Republic of China.

Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan, Hubei, 430056, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 May 30;20:6949-6962. doi: 10.2147/IJN.S515107. eCollection 2025.

DOI:10.2147/IJN.S515107

PMID:40462832

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12132069/

Abstract

INTRODUCTION

Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by excessive fat accumulation in the liver, is the most prevalent cause of chronic liver disease globally. The clinical use of pharmacological agents such as silibinin and sorafenib is limited due to poor water solubility, low bioavailability, and potential side effects, necessitating innovative therapeutic approaches.

METHODS

In this study, we developed self-assembled, carrier-free microparticles of silibinin and sorafenib (SIL-SOR-MPs) using magnetic stirring and evaluated their therapeutic effects on MASLD both in vitro and in vivo.

RESULTS

Compared to free SIL and free SOR, SIL-SOR-MPs significantly reduced lipid accumulation in HepG2 cells and effectively alleviated hepatic steatosis and liver damage in mice. Mechanistic investigations further showed that SIL-SOR-MPs more effectively down-regulated lipid synthesis genes and up-regulated genes involved in lipid oxidation.

DISCUSSION

In summary, our study highlights that carrier-free SIL-SOR-MPs demonstrate the ability to reverse the progression of MASLD and present a promising therapeutic strategy.

摘要