Trifolin inhibits the calcium-driven contraction pathway in vascular smooth muscle
Trifolin, a bioactive component of the Qingda granule, has demonstrated significant antihypertensive potential; however, its precise mechanisms of action remain largely unknown. This study aimed to investigate the antihypertensive effects of trifolin and unravel its underlying molecular mechanisms....
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1573483/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849716993290141696 |
|---|---|
| author | Renfeng Li Renfeng Li Renfeng Li Renfeng Li Jinkong Wu Jinkong Wu Jinkong Wu Jinkong Wu Meizhu Wu Meizhu Wu Meizhu Wu Meizhu Wu Farman Ali Farman Ali Farman Ali Farman Ali Yanyan Yang Hong Chen Hong Chen Hong Chen Hong Chen Zhi Guo Zhi Guo Zhi Guo Zhi Guo Dawei Lian Dawei Lian Dawei Lian Dawei Lian Aling Shen Aling Shen Aling Shen Aling Shen Jun Peng Jun Peng Jun Peng Jun Peng |
| author_facet | Renfeng Li Renfeng Li Renfeng Li Renfeng Li Jinkong Wu Jinkong Wu Jinkong Wu Jinkong Wu Meizhu Wu Meizhu Wu Meizhu Wu Meizhu Wu Farman Ali Farman Ali Farman Ali Farman Ali Yanyan Yang Hong Chen Hong Chen Hong Chen Hong Chen Zhi Guo Zhi Guo Zhi Guo Zhi Guo Dawei Lian Dawei Lian Dawei Lian Dawei Lian Aling Shen Aling Shen Aling Shen Aling Shen Jun Peng Jun Peng Jun Peng Jun Peng |
| author_sort | Renfeng Li |
| collection | DOAJ |
| description | Trifolin, a bioactive component of the Qingda granule, has demonstrated significant antihypertensive potential; however, its precise mechanisms of action remain largely unknown. This study aimed to investigate the antihypertensive effects of trifolin and unravel its underlying molecular mechanisms. The influence of trifolin on vascular contraction and relaxation and its regulatory effects on ion channels were evaluated through a vascular tension experiment. Morphological changes in the aortic tissues of mice with angiotensin Ⅱ-induced hypertension and the expression profiles of contraction-associated proteins were analyzed via hematoxylin-eosin staining and immunohistochemistry. Additionally, trifolin’s impact on calcium ion dynamics and contraction-associated protein expression in angiotensin Ⅱ-activated vascular smooth muscle cells (VSMCs) was determined through calcium flux assays and western blot analyses. Trifolin treatment decreased the constriction of isolated abdominal aortic rings induced by norepinephrine, KCl, and angiotensin Ⅱ in an endothelium-independent manner and extracellular Ca2+ influx induced by these three substances and thapsigargin. Moreover, trifolin treatment significantly reduced the abdominal aortic wall thickness and downregulated the expression of store-operated channels channel proteins (STIM1 and ORAI1) and calcium signaling-related proteins (CaM, myosin light chain kinase, and p-MLC2) in the abdominal aorta of hypertensive mice and angiotensin Ⅱ-induced VSMCs. In conclusion, calcium signaling inhibition may underlie trifolin’s antihypertensive effects and its ability to ameliorate vascular function. These findings offer new therapeutic insights for hypertension treatment. |
| format | Article |
| id | doaj-art-e4e4e1ad1e7241319459b6a16c55b060 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-e4e4e1ad1e7241319459b6a16c55b0602025-08-20T03:12:49ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15734831573483Trifolin inhibits the calcium-driven contraction pathway in vascular smooth muscleRenfeng Li0Renfeng Li1Renfeng Li2Renfeng Li3Jinkong Wu4Jinkong Wu5Jinkong Wu6Jinkong Wu7Meizhu Wu8Meizhu Wu9Meizhu Wu10Meizhu Wu11Farman Ali12Farman Ali13Farman Ali14Farman Ali15Yanyan Yang16Hong Chen17Hong Chen18Hong Chen19Hong Chen20Zhi Guo21Zhi Guo22Zhi Guo23Zhi Guo24Dawei Lian25Dawei Lian26Dawei Lian27Dawei Lian28Aling Shen29Aling Shen30Aling Shen31Aling Shen32Jun Peng33Jun Peng34Jun Peng35Jun Peng36Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaInnovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, ChinaTrifolin, a bioactive component of the Qingda granule, has demonstrated significant antihypertensive potential; however, its precise mechanisms of action remain largely unknown. This study aimed to investigate the antihypertensive effects of trifolin and unravel its underlying molecular mechanisms. The influence of trifolin on vascular contraction and relaxation and its regulatory effects on ion channels were evaluated through a vascular tension experiment. Morphological changes in the aortic tissues of mice with angiotensin Ⅱ-induced hypertension and the expression profiles of contraction-associated proteins were analyzed via hematoxylin-eosin staining and immunohistochemistry. Additionally, trifolin’s impact on calcium ion dynamics and contraction-associated protein expression in angiotensin Ⅱ-activated vascular smooth muscle cells (VSMCs) was determined through calcium flux assays and western blot analyses. Trifolin treatment decreased the constriction of isolated abdominal aortic rings induced by norepinephrine, KCl, and angiotensin Ⅱ in an endothelium-independent manner and extracellular Ca2+ influx induced by these three substances and thapsigargin. Moreover, trifolin treatment significantly reduced the abdominal aortic wall thickness and downregulated the expression of store-operated channels channel proteins (STIM1 and ORAI1) and calcium signaling-related proteins (CaM, myosin light chain kinase, and p-MLC2) in the abdominal aorta of hypertensive mice and angiotensin Ⅱ-induced VSMCs. In conclusion, calcium signaling inhibition may underlie trifolin’s antihypertensive effects and its ability to ameliorate vascular function. These findings offer new therapeutic insights for hypertension treatment.https://www.frontiersin.org/articles/10.3389/fphar.2025.1573483/fulltrifolinhypertensionvasoconstrictioncalcium signaling pathwaysmooth vascular muscle |
| spellingShingle | Renfeng Li Renfeng Li Renfeng Li Renfeng Li Jinkong Wu Jinkong Wu Jinkong Wu Jinkong Wu Meizhu Wu Meizhu Wu Meizhu Wu Meizhu Wu Farman Ali Farman Ali Farman Ali Farman Ali Yanyan Yang Hong Chen Hong Chen Hong Chen Hong Chen Zhi Guo Zhi Guo Zhi Guo Zhi Guo Dawei Lian Dawei Lian Dawei Lian Dawei Lian Aling Shen Aling Shen Aling Shen Aling Shen Jun Peng Jun Peng Jun Peng Jun Peng Trifolin inhibits the calcium-driven contraction pathway in vascular smooth muscle Frontiers in Pharmacology trifolin hypertension vasoconstriction calcium signaling pathway smooth vascular muscle |
| title | Trifolin inhibits the calcium-driven contraction pathway in vascular smooth muscle |
| title_full | Trifolin inhibits the calcium-driven contraction pathway in vascular smooth muscle |
| title_fullStr | Trifolin inhibits the calcium-driven contraction pathway in vascular smooth muscle |
| title_full_unstemmed | Trifolin inhibits the calcium-driven contraction pathway in vascular smooth muscle |
| title_short | Trifolin inhibits the calcium-driven contraction pathway in vascular smooth muscle |
| title_sort | trifolin inhibits the calcium driven contraction pathway in vascular smooth muscle |
| topic | trifolin hypertension vasoconstriction calcium signaling pathway smooth vascular muscle |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1573483/full |
| work_keys_str_mv | AT renfengli trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT renfengli trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT renfengli trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT renfengli trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT jinkongwu trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT jinkongwu trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT jinkongwu trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT jinkongwu trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT meizhuwu trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT meizhuwu trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT meizhuwu trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT meizhuwu trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT farmanali trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT farmanali trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT farmanali trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT farmanali trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT yanyanyang trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT hongchen trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT hongchen trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT hongchen trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT hongchen trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT zhiguo trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT zhiguo trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT zhiguo trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT zhiguo trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT daweilian trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT daweilian trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT daweilian trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT daweilian trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT alingshen trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT alingshen trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT alingshen trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT alingshen trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT junpeng trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT junpeng trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT junpeng trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle AT junpeng trifolininhibitsthecalciumdrivencontractionpathwayinvascularsmoothmuscle |