The Phenylethanol Glycoside Liposome Inhibits PDGF-Induced HSC Activation via Regulation of the FAK/PI3K/Akt Signaling Pathway

Molecules

Shi-Lei Zhang¹  Tao Liu¹  Long Ma¹  Shu-Ping You¹  Xiao-Yan Ye¹  Xiao-Ting Ma¹  Jun Zhao² 

[1] Department of Toxicology, School of Public Health, Xinjiang Medical University, Xinjiang Uyghur Autonomous Region, Xinyi Road No.393, Urumqi 830011, China;Key Laboratory for Uighur Medicine, Institute of Materia Medica of Xinjiang, Xinjiang Uyghur Autonomous Region, Tianshan District, Xinhua South Road No. 140, Urumqi 830004, China;

关键词: phenylethanol glycosides liposome;    hepatic stellate cells;    proliferation;    apotosis;    cell cycle;    FAK/PI3K/Akt;   

DOI  :  10.3390/molecules24183282

来源: DOAJ

【 摘 要 】

Cistanche tubulosa is a traditional Chinese herbal medicine that is widely used to regulate immunity, and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. However, the application of CPhGs is negatively affected by their poor absorption and low oral utilization. Targeted drug delivery is an important development direction for pharmaceutics. Previous studies have indicated that CPhGs could block the conduction of the signaling pathways in TGF-β1/smad and inhibit the activation of hepatic stellate cells (HSCs). The aim of this study was to evaluate the anti-hepatic fibrosis effect of CPhG liposomes by inhibiting HSC activation, promoting apoptosis, blocking the cell cycle, suppressing the conduction of signaling pathways in focal adhesion kinase(FAK)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), and determining their in vitro hepatoprotective activity. In vitro release studies demonstrated that CPhG liposomes have a sustained release effect compared to drug CPhGs. HSC proliferation was inhibited after treatment with the CPhG liposomes (29.45, 14.72, 7.36 µg/mL), with IC₅₀ values of 42.54 µg/mL in the MTT assay. Different concentrations of the CPhG liposomes could inhibit HSC proliferation, promote apoptosis, and block the cell cycle. The MTT method showed an obvious inhibition of HSC proliferation after CPhG liposome and Recombinant Rat Platelet-derived growth factor-BB(rrPDGF-BB) treatment. The levels of collagen-1, metallopeptidase inhibitor 1 (TIMP-1), α smooth muscle actin (α-SMA), and phosphorylated PI3K/Akt were downregulated, and matrix metalloproteinase-1 (MMP-1) was upregulated, by pretreatment with different concentrations of CPhG liposomes. Moreover, 29.45 μg/mL of CPhG liposomes could decrease the expression of the FAK protein and the phosphorylated PI3K and Akt protein downstream of FAK by overexpression of the FAK gene. This experiment suggests that CPhG liposomes may inhibit the activation of HSCs by inhibiting FAK and then reducing the expression of phosphorylated Akt/PI3K, thereby providing new insights into the application of CPhGs for liver fibrosis.

【 授权许可】

Unknown