Inhibitory effects of naringenin on the activation of hepatic stellate cells through activating the apoptosis signal

WU Lixia; WANG Yuwei; WU Hongyan

doi:10.6039/j.issn.1001-0408.2023.10.07

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Inhibitory effects of naringenin on the activation of hepatic stellate cells through activating the apoptosis signal

更新时间：2023-05-25

- Inhibitory effects of naringenin on the activation of hepatic stellate cells through activating the apoptosis signal
- ZHONGGUO YAOFANG Vol. 34, Issue 10, Pages: 1187-1192(2023)
- 作者机构：
  
  1.安徽省庐江县人民医院儿科，合肥　231501
  2.南京中医药大学药学院，南京　210023
  3.江苏医药职业学院医药生物技术研究院，江苏盐城　224005
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.10.07
  CLC： R965
- Published：30 May 2023，
  
  Received：02 October 2022，
  
  Revised：25 March 2023，
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吴丽霞,王雨薇,吴红雁.柚皮素通过激活凋亡信号抑制肝星状细胞活化 ^Δ[J].中国药房,2023,34(10):1187-1192.

WU Lixia,WANG Yuwei,WU Hongyan.Inhibitory effects of naringenin on the activation of hepatic stellate cells through activating the apoptosis signal[J].ZHONGGUO YAOFANG,2023,34(10):1187-1192.
吴丽霞,王雨薇,吴红雁.柚皮素通过激活凋亡信号抑制肝星状细胞活化 ^Δ[J].中国药房,2023,34(10):1187-1192. DOI： 10.6039/j.issn.1001-0408.2023.10.07.

WU Lixia,WANG Yuwei,WU Hongyan.Inhibitory effects of naringenin on the activation of hepatic stellate cells through activating the apoptosis signal[J].ZHONGGUO YAOFANG,2023,34(10):1187-1192. DOI： 10.6039/j.issn.1001-0408.2023.10.07.

摘要

目的

研究柚皮素对肝星状细胞活化的体外抑制作用及可能机制。

方法

以人正常肝细胞LO2为参照，在MTT法筛选药物干预浓度的基础上，考察柚皮素（Western blot实验和台盼蓝染色实验浓度为10、20、40 μmol/L，免疫荧光实验浓度为40 μmol/L）对人肝星状细胞LX2肝纤维化标志物蛋白[胶原纤维Ⅰ（collagenⅠ）、

-平滑肌肌动蛋白（

-SMA）]及mRNA（collagen Ⅰ前体α1-pro collagen Ⅰ、

-SMA）表达、细胞凋亡及凋亡相关蛋白[Bcl-2、Bax、剪切的胱天蛋白酶3（cleaved caspase-3）]表达的影响；选择凋亡抑制剂（Z-VAD-FMK，FMK）、铁死亡通路抑制剂ferrostatin-1、程序性死亡通路抑制剂necrostatin-1对上述作用机制进行验证。

结果

柚皮素可显著下调LX2细胞中collagen Ⅰ（柚皮素10 μmol/L除外）、

-SMA蛋白及α1-pro collagen Ⅰ（柚皮素10 μmol/L除外）、

-SMA mRNA的表达（

＜0.05），可诱导LX2细胞凋亡并提高其凋亡比例，可显著下调Bcl-2蛋白的表达并上调Bax（柚皮素10 μmol/L除外）、cleaved caspase-3（柚皮素10 μmol/L除外）蛋白的表达；FMK可逆转柚皮素对LX2细胞的上述作用（

＜0.05）。

结论

柚皮素可通过激活肝星状细胞LX2的凋亡信号来抑制其活化，从而发挥对肝纤维化的改善作用。

Abstract

OBJECTIVE

To study the inhibitory effects and possible mechanism of naringenin on the activation of hepatic stellate cells.

METHODS

Using human hepatocytes LO2 as reference， based on drug intervention concentration screened by MTT assay， the effects of naringenin （Western blot assay and trypan blue staining test in 10， 20， 40 μmol/L， immunofluorescence assay in 40 μmol/L） on the expressions of liver fibrosis markers protein （collagen Ⅰ，

-SMA） and mRNA （α1-pro collagen Ⅰ，

-SMA） in human hepatic stellate cells LX2， and the expressions of cell apoptosis and apoptosis-related proteins （Bcl-2， Bax， cleaved caspase-3） were investigated. The apoptosis agents （Z-VAD-FMK， FMK）， ferroptosis pathway inhibitor ferrostatin-1， and programmed death pathway inhibitor necrostatin-1 were used to verify the mechanism of the above effects.

RESULTS

The naringenin could significantly down-regulate protein expressions of collagen Ⅰ （except for naringenin 10 μmol/L） and

-SMA， mRNA expressions of α1-pro collagen Ⅰ （except for naringenin 10 μmol/L） and

-SMA （

＜0.05）； it also induced LX2 cell apoptosis and increased its apoptotic ratio， down-regulated the protein expression of Bcl-2 while up-regulated the protein expressions of Bax （except for naringenin 10 μmol/L） and cleaved caspase-3 （except for naringenin 10 μmol/L）. FMK could reverse above effects of naringenin on LX2 cells （

＜0.05）.

CONCLUSIONS

Naringenin can inhibit the activation of hepatic stellate cells LX2 through activating the cell apoptosis signal， which plays ameliorative role in liver fibrosis.

关键词

柚皮素肝星状细胞肝纤维化细胞凋亡信号

Keywords

hepatic stellate cellsliver fibrosiscell apoptosis signal

references

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