Schisantherin A ameliorates liver fibrosis through TGF-β1mediated activation of TAK1/MAPK and NF-κB pathways in vitro and in vivo.

Abstract

BACKGROUD:

Schisandra chinensis, a traditional Chinese medicine for liver protection, can significantly improve liver fibrosis. However, it is still unclear which active components in Schisandra chinensis play an anti-fibrosis role.

PURPOSE:

The purpose of present study was to observe the anti-fibrosis effect of schisantherin A (SCA) on liver fibrosis and explore its underlying mechanism.

METHODS:

The liver fibrosis model of mice was constructed by the progressive intraperitoneal injection of thioacetamide (TAA), and SCA (1, 2, and 4 mg/kg) was administered by gavage for 5 weeks. The biochemical indicators and inflammatory cytokines were measured, changes in the pathology of the mice liver were observed by hematoxylin & eosin (H&E) and Masson stainings for studying the anti-fibrosis effect of SCA. A hepatic stellate cell (HSCs) activation model induced by transforming growth factor-β1 (TGF-β1) was established, and the effect of SCA on the HSCs proliferation was observed by MTT assay. The expressions of target proteins related to transforming growth factor-β-activated kinase 1 (TAK1)/mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were evaluated by western blotting, immunohistochemistry or immunofluorescence analysis, to explore the potential mechanism of SCA.

RESULTS:

SCA could significantly ameliorate the pathological changes of liver tissue induced by TAA, and reduce the serum transaminase level, the hydroxyproline level and the expression of α-smooth muscle actin (α-SMA) and collagen 1A1 (COL1A1) proteins in the liver tissue. SCA could significantly lower the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the serum and liver tissue, and down-regulate the expression of target proteins related to TAK1/MAPK and NF-κB pathways in the liver tissue. The in vitro studies demonstrated that SCA significantly inhibited the proliferation and activation of HCS-T6 cells induced by TGF-β1, decreased TNF-α and IL-6 levels, and inhibited the TAK1 activation induced by TGF-β1 and then the expression of MAPK and NF-κB signaling pathway-related proteins.

CONCLUSION:

Together, SCA can ameliorate the liver fibrosis induced by TAA and the HSC-T6 cell activation induced by TGF-β1 in mice, and its mechanism may be to inhibit the HSCs activation and inflammatory response by inhibiting TGF-β1 mediated TAK1/MAPK and signal pathways.

• Authors: Haili Wang, Jinying Che, Kai Cui, Wenyue Zhuang, He Li, Jinghui Sun, Jianguang Chen, Chunmei Wang
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 88 Pg. 153609 (Jul 15 2021) ISSN: 1618-095X [Electronic] Germany
• PMID: 34126414 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier GmbH.

Chemical References

• Cyclooctanes
• Cytokines
• Dioxoles
• Lignans
• NF-kappa B
• Transforming Growth Factor beta1
• Thioacetamide
• schizandrer A
• Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinases
• MAP kinase kinase kinase 7

Topics

• Animals
• Cell Line
• Cyclooctanes (pharmacology)
• Cytokines (metabolism)
• Dioxoles (pharmacology)
• Hepatic Stellate Cells (drug effects)
• Lignans (pharmacology)
• Liver Cirrhosis (drug therapy, metabolism, pathology)
• MAP Kinase Kinase Kinases (metabolism)
• Male
• Mice, Inbred ICR
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Rats
• Signal Transduction (drug effects)
• Thioacetamide (toxicity)
• Transforming Growth Factor beta1 (metabolism)