Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ
Cynarin, a caffeoylquinic acid compound that was mainly extracted from Cynara scolymus L., displays various activities such as antioxidant, antibacterial, choleretic, and hepatoprotective functions. However, the target of cynarin and the mechanism of its hepatoprotective effect are still unclear. To...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2022-10-01
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| Series: | Open Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/chem-2022-0192 |
| _version_ | 1811194164009762816 |
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| author | Ding Yong Tao Congcong Chen Qian Chen Lulu Hu Xianwen Li Mingyu Wang Shicong Jiang Fuquan |
| author_facet | Ding Yong Tao Congcong Chen Qian Chen Lulu Hu Xianwen Li Mingyu Wang Shicong Jiang Fuquan |
| author_sort | Ding Yong |
| collection | DOAJ |
| description | Cynarin, a caffeoylquinic acid compound that was mainly extracted from Cynara scolymus L., displays various activities such as antioxidant, antibacterial, choleretic, and hepatoprotective functions. However, the target of cynarin and the mechanism of its hepatoprotective effect are still unclear. To find cynarin’s target, we performed molecular docking analysis, fluorescence-based ligand-binding assay, and reporter gene system assay. Our results indicated that cynarin was a partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ). Further studies showed that cynarin significantly inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and activation of rat CFSC-8G hepatic stellate cells (HSCs). Our results also revealed that cynarin inhibited PDGF-BB-induced extracellular regulated protein kinase (ERK) and v-akt murine thymoma viral oncogene homolog (AKT) phosphorylation in HSCs. In addition, this inhibition effect was PPARγ dependent since the knockdown of PPARγ significantly attenuated the effects of cynarin on PDGF-BB-induced p-ERK, p-AKT, and α-smooth muscle actin (α-SMA) expressions. Therefore, this study suggests that cynarin is a promising antifibrotic lead compound that inhibits the activation of HSCs, and it works by targeting PPARγ. |
| first_indexed | 2024-04-12T00:21:20Z |
| format | Article |
| id | doaj.art-8793774e22434bea97155d775c9e33b9 |
| institution | Directory Open Access Journal |
| issn | 2391-5420 |
| language | English |
| last_indexed | 2024-04-12T00:21:20Z |
| publishDate | 2022-10-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Chemistry |
| spelling | doaj.art-8793774e22434bea97155d775c9e33b92022-12-22T03:55:43ZengDe GruyterOpen Chemistry2391-54202022-10-012011121112910.1515/chem-2022-0192Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγDing Yong0Tao Congcong1Chen Qian2Chen Lulu3Hu Xianwen4Li Mingyu5Wang Shicong6Jiang Fuquan7Yunnan Provincial Key Laboratory of Forest Biotechnology, School of Life Sciences, Southwest Forestry University, Kunming 650224, ChinaYunnan Provincial Key Laboratory of Forest Biotechnology, School of Life Sciences, Southwest Forestry University, Kunming 650224, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaFujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou Pien Tze Huang Pharmaceutical, Co., Ltd., Zhangzhou 363000, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, ChinaCynarin, a caffeoylquinic acid compound that was mainly extracted from Cynara scolymus L., displays various activities such as antioxidant, antibacterial, choleretic, and hepatoprotective functions. However, the target of cynarin and the mechanism of its hepatoprotective effect are still unclear. To find cynarin’s target, we performed molecular docking analysis, fluorescence-based ligand-binding assay, and reporter gene system assay. Our results indicated that cynarin was a partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ). Further studies showed that cynarin significantly inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and activation of rat CFSC-8G hepatic stellate cells (HSCs). Our results also revealed that cynarin inhibited PDGF-BB-induced extracellular regulated protein kinase (ERK) and v-akt murine thymoma viral oncogene homolog (AKT) phosphorylation in HSCs. In addition, this inhibition effect was PPARγ dependent since the knockdown of PPARγ significantly attenuated the effects of cynarin on PDGF-BB-induced p-ERK, p-AKT, and α-smooth muscle actin (α-SMA) expressions. Therefore, this study suggests that cynarin is a promising antifibrotic lead compound that inhibits the activation of HSCs, and it works by targeting PPARγ.https://doi.org/10.1515/chem-2022-0192cynarinpparγhepatic stellate cellspdgf-bb |
| spellingShingle | Ding Yong Tao Congcong Chen Qian Chen Lulu Hu Xianwen Li Mingyu Wang Shicong Jiang Fuquan Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ Open Chemistry cynarin pparγ hepatic stellate cells pdgf-bb |
| title | Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ |
| title_full | Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ |
| title_fullStr | Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ |
| title_full_unstemmed | Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ |
| title_short | Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ |
| title_sort | cynarin inhibits pdgf bb induced proliferation and activation in hepatic stellate cells through pparγ |
| topic | cynarin pparγ hepatic stellate cells pdgf-bb |
| url | https://doi.org/10.1515/chem-2022-0192 |
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