Mechanism of action of Eupolyphaga steleophaga in improving nonalcoholic steatohepatitis by regulating syndecan 3

Guangyue YANG; Le TAO; Wei ZHANG; Xuling LIU; Wenting MA; Liu WU; Tiantian SUN; Hao JIANG; Cheng LIU

doi:10.3969/j.issn.1001-5256.2022.07.012

Volume 38 Issue 7

Jul. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(7): 1513-1520

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Mechanism of action of Eupolyphaga steleophaga in improving nonalcoholic steatohepatitis by regulating syndecan 3

DOI: 10.3969/j.issn.1001-5256.2022.07.012

a.
Laboratory of Liver Diseases, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
b.
Department of Infectious Diseases, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
c.
Central Laboratory, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China

Research funding:

National Natural Science Foundation of China (81673788);

National Natural Science Foundation of China (81873136);

National Natural Science Foundation of China (81803898);

National Natural Science Foundation of China (81803232);

National Natural Science Foundation of China (82004106);

Shanghai Natural Science Foundation of China (20ZR1450300);

Putuo District of Shanghai Innovation Project (ptkwws201817);

Putuo District of Shanghai Innovation Project (ptkwws201904);

Putuo District of Shanghai Innovation Project (ptkwws202223);

Putuo District of Shanghai Innovation Project (ptkwws202112);

Scientific Research Fund of Shanghai Sixth People's Hospital Medical Group (21-ly-02);

Xinglin Scholar of Chengdu University of Traditional Chinese Medicine (YYZX2020117)

More Information

Corresponding author: LIU Cheng, liucheng0082010@163.com(ORCID: 0000-0002-8741-6169)
Received Date: 2021-11-23
Accepted Date: 2022-01-21
Published Date: 2022-07-20

Abstract

Abstract

Objective To investigate the effect of Eupolyphaga steleophaga on nonalcoholic steatohepatitis induced by choline-deficient L-amino acid-defined diet (CDAA) and its mechanism by regulating syndecan 3. Methods A total of 18 male C57BL/6 mice were randomly divided into choline-sufficient L-amino acid-defined diet (CSAA) group, CDAA group, and CDAA+Eupolyphaga steleophaga group (CDAA+T group). Since week 12 of modeling, the mice in the CDAA+T group were fed with Eupolyphaga steleophaga 0.108 g/kg (10 times that the dose for adults) by gavage, and those in the CSAA and CDAA groups were given an equal volume of normal saline by gavage. Serum and liver tissue samples were collected at the end of week 18 to measure liver function, total cholesterol (TC), and triglyceride (TG) and observe liver pathology. Quantitative real-time PCR was used to measure the mRNA expression levels of transforming growth factor β (TGFβ), α-smooth muscle actin (α-SMA), collagen type Ⅰ α1 (Col1α1), and SDC3; the mRNA expression of SDC3 was measured in human and mouse primary hepatocytes, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), and Kupffer cells (KCs), and SDC3 was silenced by si-RNA to investigate the role of SDC3 in HSC activation. Western blotting was used to measure the protein expression of SDC3. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK test or the least significant difference t-test was used for further comparison between two groups. Results Compared with the CSAA group, the CDAA group had significant increases in liver function parameters [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and the levels of TC and TG in serum and the liver (all P < 0.05), and compared with the CDAA group, the CDAA+T group had significant reductions in the serum levels of ALT, AST, TC, and TG (all P < 0.05). HE staining showed that the CDAA group had marked hepatocyte steatosis and increased inflammatory cell infiltration, and the CDAA+T group had alleviated inflammatory cell infiltration; Sirius Red staining showed a significant increase in collagen hyperplasia in the CDAA group and a significant reduction in collagen hyperplasia in the CDAA+T group; oil red staining showed marked fat deposition in the CDAA group and a reduction in fat deposition in the CDAA+T group. Compared with the CDAA group, the CDAA+T group had significant reductions in the mRNA expression levels of TGFβ, SDC3, α-SMA, and COL1α1 and the protein expression levels of SDC3 and α-SMA. Immunohistochemistry showed a very low expression level of SDC3 in the CSAA group and a significant increase in the expression of SDC3 in the CDAA group, mainly in the interstitial cells, and there was a significant reduction after Eupolyphaga steleophaga intervention (all P < 0.05). PCR results showed the highest expression of SDC3 in HSCs of human and mouse liver (all P < 0.001). LX2 cells were cultured in vitro, and Eupolyphaga steleophaga treatment significantly reduced the upregulation of α-SMA and Col1α1 induced by TGFβ, while after SDC3 gene silencing, Eupolyphaga steleophaga did not inhibit the increases in α-SMA and Col1α1 (all P < 0.05). Conclusion Eupolyphaga steleophaga can significantly improve nonalcoholic steatohepatitis induced by CDAA, possibly by regulating the expression of SDC3 in HSCs.
- Eupolyphaga,
- Non-alcoholic Steatohepatitis,
- Syndecan-3

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References(21)

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Mechanism of action of Eupolyphaga steleophaga in improving nonalcoholic steatohepatitis by regulating syndecan 3

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Mechanism of action of Eupolyphaga steleophaga in improving nonalcoholic steatohepatitis by regulating syndecan 3

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