Inhibitory Effect of Curcumin and Its Derivatives on TGF-β Induced Fibrosis of LX-2 Cells
10.13748/j.cnki.issn1007-7693.20233169
- VernacularTitle:姜黄素及其衍生物对TGF-β诱导的LX-2细胞纤维化的抑制作用研究
- Author:
Yidan SHAO
1
;
Tingting SHI
1
;
Yanmei ZHAO
1
;
Xi ZOU
1
;
Jianjun XI
1
;
Jing ZHANG
1
;
Xiaojie JIANG
1
;
Rangxiao ZHUANG
1
Author Information
1. Hangzhou Xixi Hospital, Hangzhou 310023, China
- Publication Type:Journal Article
- Keywords:
curcumin ； derivative ； liver fibrosis ；LX-2 ； TGF-β
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(13):1750-1757
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To study the inhibitory effect and mechanism of curcumin and its derivatives A and B on TGF-β induced LX-2 cell fibrosis.
METHODS
Established the liver fibrosis model of LX-2 cells induced by TGF-β(10 ng·mL−1).The effects on cell proliferation were detected by CCK-8. The effects on cell apoptosis was detected by flow cytometry. The effects on fibrosis related factors(Collagen I, Collagen Ⅳ, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, MMP2, MMP9, TIMP1 and TIMP2) protein expression and gene transcription levels were detected by Western blotting and q-PCR.
RESULTS
The curcumin and its derivative A and B had the inhibition effects on normal LX-2 cells, and the IC25 values were 15.7, 2.6, 10.2 μmol·L−1, respectively. Compared to the model group, the curcumin(15.7 μmol·L−1) and its derivative A(2.6 μmol·L−1) and B(10.2 μmol·L−1) had the significant inhibition effects on cell proliferation of the TGF-β induced LX-2 cells(P<0.05). The cell apoptosis rate of curcumin derivative B group was higher than the model group(P<0.05). Collagen I, Fibronectin, Vimentin, α-SMA, TGFβR1 and TIMP-1 protein expression levels in curcumin group were lower, while the protein expression level of MMP-9 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, TIMP-1 and TIMP-2 in curcumin derivative A group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, TIMP-1 and TIMP-2 in curcumin derivative B group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The gene transcription levels of Collagen I, Fibronectin, α-SMA and TIMP-1 in curcumin group were lower(P<0.05). The gene transcription levels of Collagen I, Fibronectin and α-SMA in curcumin derivative A and B groups were lower(P<0.05).
CONCLUSION
Curcumin and its derivatives A and B inhibit the abnormal activation and proliferation of TGF-β-induced LX-2 cells, inhibit the excessive secretion and accumulation of its extracellular matrix components, and promote its degradation, thus playing an anti-fibrotic effect in vitro, especially the curcumin derivative B.
