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Can J Physiol Pharmacol. 2016 Sep;94(9):987-95. doi: 10.1139/cjpp-2016-0157. Epub 2016 Apr 28.

Cryptolepine derivative-6h inhibits liver fibrosis in TGF-β1-induced HSC-T6 cells by targeting the Shh pathway.

He YH1,2,3, Li Z1,2,3, Ni MM1,2,3, Zhang XY1,2,3, Li MF1,2,3, Meng XM1,2,3, Huang C1,2,3, Li J1,2,3.

Author information

1
a School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
2
b Institute for Liver Diseases, Anhui Medical University, ILD-AMU, Hefei 230032, China.
3
c Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China.

Abstract

Liver fibrosis is a worldwide problem with a significant morbidity and mortality. Cryptolepis sanguinolenta (family Periplocaceae) is widely used in West African countries for the treatment of malaria, as well as for some other diseases. However, the role of C. sanguinolenta in hepatic fibrosis is still unknown. It has been reported that Methyl-CpG binding protein 2 (MeCP2) had a high expression in liver fibrosis and played a central role in its pathobiology. Interestingly, we found that a cryptolepine derivative (HZ-6h) could inhibit liver fibrosis by reducing MeCP2 expression, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) in protein levels in vitro. Meanwhile, we also found that HZ-6h could reduce the cell viability and promote apoptosis of hepatic stellate cells (HSCs) treated with transforming growth factor beta 1(TGF-β1). Then, we investigated the potential molecular mechanisms and found that HZ-6h blocked Shh signaling in HSC-T6 cells, resulting in the decreased protein expression of Patched-1 (PTCH-1), Sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (GLI1). In short, these results indicate that HZ-6h inhibits liver fibrosis by downregulating MeCP2 through the Shh pathway in TGF-β1-induced HSC-T6 cells.

KEYWORDS:

MeCP2; Shh signaling; cryptolepine; cryptolépine; fibrose hépatique; liver fibrosis; signalisation de Shh

PMID:
27295431
DOI:
10.1139/cjpp-2016-0157
[Indexed for MEDLINE]

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