Tohoku J. Exp. Med., 2023 December, 261(4)
Liposomal Silybin Improves Glucose and Lipid Metabolisms in Type 2 Diabetes Mellitus Complicated with Non-Alcoholic Fatty Liver Disease via AMPK/TGF-β1/Smad Signaling
Jialuo Cai,1,2,* Yilin Zhu,3,* Xiaoping Li,2 Guiming Deng,4 Yuanshan Han,4Feiyun Yuan,5 Gangqiang Yi6 and Xinhua Xia1
1School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
2Preventive Treatment of Disease Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
3Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, China
4Scientific Research Section, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
5Library, Hunan University of Chinese Medicine, Changsha, Hunan, China
6Party Committee, Hunan University of Chinese Medicine, Changsha, Hunan, China
Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-β1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-β1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.
Key words —— diabetes mellitus; glycolipid metabolism; liposomes; non-alcoholic fatty liver disease; silybin
Tohoku J. Exp. Med., 2023 December, 261(4), 257-265.
*These two authors contributed equally to this work.
Correspondence: Xinhua Xia, School of Pharmacy, Hunan University of Chinese Medicine, No. 300, Xueshi Road, Hanpu Science & Education Garden, Yuelu District, Changsha, Hunan 410208, China.
e-mail: xiaxinhua001@hnucm.edu.cn