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

Autor: Long Ma, Jun Zhao, Xiao-Ting Ma, Shu-Ping You, Tao Liu, Shi-Lei Zhang, Xiao-Yan Ye
Rok vydání: 2019
Předmět:
Cistanche
Becaplermin
Pharmaceutical Science
Apoptosis
Analytical Chemistry
Phosphatidylinositol 3-Kinases
Drug Delivery Systems
0302 clinical medicine
apotosis
Drug Discovery
Glycosides
Medicine
Chinese Traditional
0303 health sciences
Liposome
biology
Chemistry
phenylethanol glycosides liposome
Phenylethyl Alcohol
Cell biology
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Molecular Medicine
Phosphorylation
cell cycle
hepatic stellate cells
Signal transduction
Platelet-derived growth factor receptor
proliferation
Article
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
Animals
Humans
MTT assay
FAK/PI3K/Akt
Physical and Theoretical Chemistry
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
030304 developmental biology
Organic Chemistry
Immunity
Rats
Gene Expression Regulation
Focal Adhesion Kinase 1
Liposomes
biology.protein
Hepatic stellate cell
Proto-Oncogene Proteins c-akt
Zdroj: Molecules
Volume 24
Issue 18
Molecules, Vol 24, Iss 18, p 3282 (2019)
ISSN: 1420-3049
DOI: 10.3390/molecules24183282
Popis: 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-&beta
1/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 µ
g/mL), with IC50 values of 42.54 µ
g/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), &alpha
smooth muscle actin (&alpha
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 &mu
g/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.
Databáze: OpenAIRE
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