Chemical Characterization and Atherosclerosis Alleviation Effects of Gypenosides from Gynostemma pentaphyllum through Ameliorating Endothelial Dysfunction via the PCSK9/LOX-1 Pathway
Dietary saponins have the potential to ameliorate atherosclerosis (AS). Gypenosides of Gynostemma pentaphyllum (GPs) have been used as functional foods to exhibit antiatherosclerotic activity. The present study aimed to explore the protective effect, underlying mechanism and active substances of GPs on AS in vivo and in vitro. Results demonstrated GPs administration reduced the serum concentrations of TC and LDL-C, upregulated the plasma HDL-C content, inhibited the secretion of ICAM-1, VCAM-1, and MCP-1, and alleviated vascular lesions in VitD3 plus high cholesterol diet-induced AS rats as well as reduced adhesion factors levels in ox-LDL-stimulated HUVECs, which was potentially associated with suppressing PCSK9/LOX-1 pathway. Further activity-guided phytochemical investigation of GPs led to the identification of five new dammarane-type glycosides (1-5) and ten known analogs (6-15). Bioassay evaluation showed compounds 1, 6, 7, 12, 13, and 14 observably reduced the expressions of PCSK9 and LOX-1, as well as the secretion of adhesion factors in injured HUVECs. Molecular docking experiments suggested that the active saponins of GPs might bind to the allosteric pocket of PCSK9 located at the catalytic and C-terminal domains, and 2α-OH-protopanaxadiol-type gypenosides might exert a higher affinity for an allosteric binding site on PCSK9 by hydrogen-bond interaction with ARG-458. These findings provide new insights into the potential nutraceutical application of GPs and their bioactive compounds in the prevention and discovery of novel therapeutic strategies for AS.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:70 |
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| Enthalten in: |
Journal of agricultural and food chemistry - 70(2022), 38 vom: 28. Sept., Seite 11944-11957 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Ya-Ping [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.09.2022 Date Revised 05.10.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jafc.2c02681 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346375967 |
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| 100 | 1 | |a Huang, Ya-Ping |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Chemical Characterization and Atherosclerosis Alleviation Effects of Gypenosides from Gynostemma pentaphyllum through Ameliorating Endothelial Dysfunction via the PCSK9/LOX-1 Pathway |
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| 500 | |a Date Completed 29.09.2022 | ||
| 500 | |a Date Revised 05.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Dietary saponins have the potential to ameliorate atherosclerosis (AS). Gypenosides of Gynostemma pentaphyllum (GPs) have been used as functional foods to exhibit antiatherosclerotic activity. The present study aimed to explore the protective effect, underlying mechanism and active substances of GPs on AS in vivo and in vitro. Results demonstrated GPs administration reduced the serum concentrations of TC and LDL-C, upregulated the plasma HDL-C content, inhibited the secretion of ICAM-1, VCAM-1, and MCP-1, and alleviated vascular lesions in VitD3 plus high cholesterol diet-induced AS rats as well as reduced adhesion factors levels in ox-LDL-stimulated HUVECs, which was potentially associated with suppressing PCSK9/LOX-1 pathway. Further activity-guided phytochemical investigation of GPs led to the identification of five new dammarane-type glycosides (1-5) and ten known analogs (6-15). Bioassay evaluation showed compounds 1, 6, 7, 12, 13, and 14 observably reduced the expressions of PCSK9 and LOX-1, as well as the secretion of adhesion factors in injured HUVECs. Molecular docking experiments suggested that the active saponins of GPs might bind to the allosteric pocket of PCSK9 located at the catalytic and C-terminal domains, and 2α-OH-protopanaxadiol-type gypenosides might exert a higher affinity for an allosteric binding site on PCSK9 by hydrogen-bond interaction with ARG-458. These findings provide new insights into the potential nutraceutical application of GPs and their bioactive compounds in the prevention and discovery of novel therapeutic strategies for AS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gynostemma pentaphyllum | |
| 650 | 4 | |a PCSK9 | |
| 650 | 4 | |a atherosclerosis | |
| 650 | 4 | |a endothelial dysfunction | |
| 650 | 4 | |a gypenosides | |
| 650 | 7 | |a Cholesterol, LDL |2 NLM | |
| 650 | 7 | |a Plant Extracts |2 NLM | |
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| 700 | 1 | |a Wang, Yun-Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yuan-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Cui-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Xin-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Bi-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Wen-Cai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Zhi-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Ke |e verfasserin |4 aut | |
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