Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats
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...
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| Format: | Article |
| Language: | zho |
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Editorial Office of Journal of Army Medical University
2022-07-01
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| Series: | 陆军军医大学学报 |
| Subjects: | |
| Online Access: | http://aammt.tmmu.edu.cn/Upload/rhtml/202111062.htm |
| _version_ | 1817969442313732096 |
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| author | HUANG Yi XIA Li LEI Qingsong ZHANG Changjiang |
| author_facet | HUANG Yi XIA Li LEI Qingsong ZHANG Changjiang |
| author_sort | HUANG Yi |
| collection | DOAJ |
| description | 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 (P < 0.05), and remarkably improved hepatic fibrosis and alleviated liver injury in rats. ELISA indicated notable declines in TNF-α, IL-1β and IL-18 levels in rats after intervention of medium- and high-dose SSD (P < 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.
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| first_indexed | 2024-04-13T20:21:15Z |
| format | Article |
| id | doaj.art-8ad08a4636b44cb983633b12b2a04483 |
| institution | Directory Open Access Journal |
| issn | 2097-0927 |
| language | zho |
| last_indexed | 2024-04-13T20:21:15Z |
| publishDate | 2022-07-01 |
| publisher | Editorial Office of Journal of Army Medical University |
| record_format | Article |
| series | 陆军军医大学学报 |
| spelling | doaj.art-8ad08a4636b44cb983633b12b2a044832022-12-22T02:31:32ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272022-07-0144141410142010.16016/j.2097-0927.202111062Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in ratsHUANG Yi0XIA Li1LEI Qingsong2ZHANG Changjiang3Department of Hepatic Diseases, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021Department of Hepatic Diseases, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, ChinaDepartment of Hepatic Diseases, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021 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 (P < 0.05), and remarkably improved hepatic fibrosis and alleviated liver injury in rats. ELISA indicated notable declines in TNF-α, IL-1β and IL-18 levels in rats after intervention of medium- and high-dose SSD (P < 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. http://aammt.tmmu.edu.cn/Upload/rhtml/202111062.htmsaikosaponin dhepatic fibrosisinflammationnod-like receptor protein 3 inflammasometlr4/nf-κb signalingpathway |
| spellingShingle | HUANG Yi XIA Li LEI Qingsong ZHANG Changjiang Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats 陆军军医大学学报 saikosaponin d hepatic fibrosis inflammation nod-like receptor protein 3 inflammasome tlr4/nf-κb signaling pathway |
| title | Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats |
| title_full | Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats |
| title_fullStr | Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats |
| title_full_unstemmed | Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats |
| title_short | Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats |
| title_sort | protective effects and mechanism of saikosaponin d on immune hepatic fibrosis in rats |
| topic | saikosaponin d hepatic fibrosis inflammation nod-like receptor protein 3 inflammasome tlr4/nf-κb signaling pathway |
| url | http://aammt.tmmu.edu.cn/Upload/rhtml/202111062.htm |
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