Saikosaponin-d alleviates hepatic fibrosis through regulating GPER1/autophagy signaling.

Abstract

BACKGROUND:

Hepatic fibrosis is the final pathway of chronic liver disease characterized by excessive accumulation of extracellular matrix (ECM), which eventually develop into cirrhosis and liver cancer. Emerging studies demonstrated that Saikosaponin-d (SSd) exhibits a protective role in liver fibrosis. However, the mechanism underlying anti-liver fibrosis of SSd in vivo and in vitro remains unclear.

METHODS AND RESULTS:

Transforming growth factor (TGF)-β and carbon tetrachloride (CCl4) were used for creating liver fibrosis model in vitro and in vivo, respectively. The role of SSd in regulating liver fibrosis was assessed through Sirius red and Masson staining, and IHC assay. We found that SSd attenuated remarkably CCl4-induced liver fibrosis as evidenced by decreased collagen level, and decreased expression of fibrotic markers Col 1 and α-SMA. Meanwhile, SSd repressed autophagy activation as suggested by decreased BECN1 expression and increased p62 expression. Compared with HSCs from CCl4-treated group, the primary HSCs from SSd-treated mice exhibited a marked inactivation of autophagy. Mechanistically, SSd treatment enhanced the expression of GPER1 in primary HSCs and in TGF-β-treated LX-2 cells. GPER1 agonist G1 repressed autophagy activation, whereas GPER1 antagonist G15 activated autophagy and G15 also damaged the function of SSd on suppressing autophagy, leading to subsequent increased levels of fibrotic marker level in LX-2 cells.

CONCLUSIONS:

Our findings highlight that SSd alleviates hepatic fibrosis by regulating GPER1/autophagy pathway.

• Authors: Yirong Chen, Renye Que, Na Zhang, Liubing Lin, Mengen Zhou, Yong Li
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 48 Issue 12 Pg. 7853-7863 (Dec 2021) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 34714484 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• GPER1 protein, mouse
• Receptors, Estrogen
• Receptors, G-Protein-Coupled
• Saponins
• Transforming Growth Factor beta
• Oleanolic Acid
• Carbon Tetrachloride
• saikosaponin D

Topics

• Animals
• Autophagy (physiology)
• Carbon Tetrachloride (pharmacology)
• Cells, Cultured
• China
• Fibrosis
• Hepatic Stellate Cells (drug effects, metabolism)
• Humans
• Liver (metabolism)
• Liver Cirrhosis (drug therapy, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Oleanolic Acid (analogs & derivatives, metabolism, pharmacology)
• Receptors, Estrogen (metabolism)
• Receptors, G-Protein-Coupled (metabolism)
• Saponins (metabolism, pharmacology)
• Signal Transduction
• Transforming Growth Factor beta (metabolism)