Open Access

Estrogen receptor‑β‑dependent effects of saikosaponin‑d on the suppression of oxidative stress‑induced rat hepatic stellate cell activation

  • Authors:
    • Renye Que
    • Yanting Shen
    • Jianlin Ren
    • Zhihui Tao
    • Xiaoyan Zhu
    • Yong Li
  • View Affiliations

  • Published online on: December 22, 2017     https://doi.org/10.3892/ijmm.2017.3349
  • Pages: 1357-1364
  • Copyright: © Que et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Saikosaponin-d (SSd) is one of the major triterpenoid saponins derived from Bupleurum falcatum L., which has been reported to possess antifibrotic activity. At present, there is little information regarding the potential target of SSd in hepatic stellate cells (HSCs), which serve an important role in excessive extracellular matrix (ECM) deposition during the pathogenesis of hepatic fibrosis. Our recent study indicated that SSd may be considered a novel type of phytoestrogen with estrogen‑like actions. Therefore, the present study aimed to investigate the effects of SSd on the proliferation and activation of HSCs, and the underlying mechanisms associated with estrogen receptors. In the present study, a rat HSC line (HSC‑T6) was used and cultured with dimethyl sulfoxide, SSd, or estradiol (E2; positive control), in the presence or absence of three estrogen receptor (ER) antagonists [ICI‑182780, methylpiperidinopyrazole (MPP) or (R,R)-tetrahydrochrysene (THC)], for 24 h as pretreatment. Oxidative stress was induced by exposure to hydrogen peroxide for 4 h. Cell proliferation was assessed by MTT growth assay. Malondialdehyde (MDA), CuZn-superoxide dismutase (CuZn-SOD), tissue inhibitor of metalloproteinases-1 (TIMP-1), matrix metalloproteinase-1 (MMP-1), transforming growth factor-β1 (TGF-β1), hydroxyproline (Hyp) and collagen-1 (COL1) levels in cell culture supernatants were determined by ELISA. Reactive oxygen species (ROS) was detected by flow cytometry. Total and phosphorylated mitogen-activated protein kinases (MAPKs) and α-smooth muscle actin (α-SMA) were examined by western blot analysis. TGF-β1 mRNA expression was determined by RT-quantitative (q)PCR. SSd and E2 were able to significantly suppress oxidative stress‑induced proliferation and activation of HSC‑T6 cells. Furthermore, SSd and E2 were able to reduce ECM deposition, as demonstrated by the decrease in transforming growth factor‑β1, hydroxyproline, collagen‑1 and tissue inhibitor of metalloproteinases‑1, and by the increase in matrix metalloproteinase‑1. These results suggested that the possible molecular mechanism could involve downregulation of the reactive oxygen species/mitogen‑activated protein kinases signaling pathway. Finally, the effects of SSd and E2 could be blocked by co‑incubation with ICI‑182780 or THC, but not MPP, thus indicating that ERβ may be the potential target of SSd in HSC‑T6 cells. In conclusion, these findings suggested that SSd may suppress oxidative stress‑induced activation of HSCs, which relied on modulation of ERβ.
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March 2018
Volume 41 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Que, R., Shen, Y., Ren, J., Tao, Z., Zhu, X., & Li, Y. (2018). Estrogen receptor‑β‑dependent effects of saikosaponin‑d on the suppression of oxidative stress‑induced rat hepatic stellate cell activation. International Journal of Molecular Medicine, 41, 1357-1364. https://doi.org/10.3892/ijmm.2017.3349
MLA
Que, R., Shen, Y., Ren, J., Tao, Z., Zhu, X., Li, Y."Estrogen receptor‑β‑dependent effects of saikosaponin‑d on the suppression of oxidative stress‑induced rat hepatic stellate cell activation". International Journal of Molecular Medicine 41.3 (2018): 1357-1364.
Chicago
Que, R., Shen, Y., Ren, J., Tao, Z., Zhu, X., Li, Y."Estrogen receptor‑β‑dependent effects of saikosaponin‑d on the suppression of oxidative stress‑induced rat hepatic stellate cell activation". International Journal of Molecular Medicine 41, no. 3 (2018): 1357-1364. https://doi.org/10.3892/ijmm.2017.3349