Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats

Yi HUANG; Li XIA; Qingsong LEI; Changjiang ZHANG; Huabao LIU; Lin LI

doi:10.16016/j.2097-0927.202111062

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Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats

Basic Medicine | 更新时间：2026-01-09

- Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats
- Journal of Army Medical University Vol. 44, Issue 14, Pages: 1410-1420(2022)
- 作者机构：
  
  1.400021 重庆，重庆市中医院肝病科
  2.400030 重庆，重庆大学附属肿瘤医院肿瘤放射治疗中心
- 作者简介：
- 基金信息：
  
  the General Program of Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0049);the Special Project of Performance Incentive and Guidance in Chongqing Scientific Research Institutes(jxyn2020-4)
- DOI：10.16016/j.2097-0927.202111062
  CLC： R282.71;R285.5;R575
- Received：09 November 2021，
  
  Revised：2022-03-01，
  
  Published：30 July 2022
- 稿件说明：
移动端阅览
Yi HUANG, Li XIA, Qingsong LEI, et al. Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats[J]. Journal of Army Medical University, 2022, 44(14): 1410-1420.
DOI：

Yi HUANG, Li XIA, Qingsong LEI, et al. Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats[J]. Journal of Army Medical University, 2022, 44(14): 1410-1420. DOI： 10.16016/j.2097-0927.202111062.

摘要

目的

结合网络药理学分析与动物实验验证，探讨柴胡皂苷D(

saikosaponin D

，SSD)对猪血清诱导的大鼠免疫性肝纤维化的保护作用及机制。

方法

网络药理学分析方法获得SSD与自身免疫性肝病的潜在靶点，利用STRING数据库和Cytoscape软件构建蛋白相互作用网络图。利用DAVID数据库对潜在靶点进行KEGG通路富集分析。制备大鼠免疫性肝纤维化模型，SSD干预后ELISA检测大鼠血清ALT、AST、TNF-α、IL-1β和IL-18水平，HE染色观察大鼠肝脏病理改变，Western blot检测大鼠肝脏组织中NLRP3、ASC、Caspase-1、GSDMD、TLR4、Myd88、p65及p-p65蛋白的表达。

结果

通过筛选获得SSD与自身免疫性肝病的潜在靶点177个，KEGG富集分析得到与免疫系统相关的通路主要包括NOD样受体信号通路等，获得潜在靶点在NOD样受体信号通路中的富集情况。实验研究显示与模型组

比较，高剂量SSD可显著降低大鼠血清中ALT和AST水平(

0.05)；病理组织学检测显示SSD可显著改善大鼠肝脏纤维化程度，减轻肝脏损伤；ELISA检测显示中、高剂量SSD可显著降低大鼠血清中TNF-α、IL-1β和IL-18的水平(

0.05)；Western blot检测显示SSD可明显下调NLRP3、ASC、Caspase-1、GSDMD、TLR4、Myd88和p65蛋白的水平，并抑制p65的磷酸化。

结论

SSD能减少免疫性肝纤维化大鼠血清中炎性因子释放、减轻肝脏细胞损伤，其机制可能与调控TLR4/NF-κB和NLRP3炎症小体信号通路有关。

Abstract

Objective

To explore the effects and mechanism of saikosaponin D (SSD) on immune hepatic fibrosis induced by porcine serum in rats through network pharmacology analysis and animal experimental verification.

Methods

The potential targets for SSD and autoimmune hepatic diseases were obtained based on network pharmacology analysis

and the protein interaction network was constructed using STRING database and Cytoscape software. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was subsequently performed with DAVID database. Then the rat model of immune hepatic fibrosis was prepared and further intervened with SSD. Serum levels of ALT

AST

TNF-α

IL-1β and IL-18 were measured by ELISA. The pathological changes of rat liver were observed using HE staining; and Western blotting was conducted to detect the ptotein expression of NLRP3

ASC

Caspase-1

GSDMD

Toll-like receptor 4 (TLR4)

myeloid differentiation primary response 88 (Myd88)

p65 and p-p65 in rat liver tissues.

Results

A total of 177 potential targets of SSD and autoimmune hepatic diseases were collected. Enrichment analysis showed that the immune system-related pathways were mainly NOD-like receptor signaling pathway

and the enrichment of potential targets in this signaling pathway was obtained. As compared with the model group

high-dose SSD significantly reduced the serum levels of ALT and AST in rats (

0.05)

and remarkably improved hepatic fibrosis and alleviated liver injury in rat

s. ELISA indicated notable declines in TNF-α

IL-1β and IL-18 levels in rats after intervention of medium- and high-dose SSD (

0.05). Western blotting also suggested that SSD greatly down-regulated the protein levels of NLRP3

ASC

Caspase-1

GSDMD

TLR4

Myd88 and p65

and inhibited the phosphorylation of p65.

Conclusion

SSD reduces the release of inflammatory factors in serum and alleviates the injury of liver cells in rats with immune hepatic fibrosis

which may be related to the regulation of TLR4/NF-κB and NLRP3 inflammasome signaling pathways.

关键词

Keywords

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