5,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive rats
Abstract Hypertension is one of the most serious chronic diseases. This study will focus on the systemic antihypertensive mechanisms of 5,7-dihydroxyflavone from in silico simulations to in vivo validations. In-silico studies were applied by network pharmacology, molecular docking, and molecular dyn...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84259-6 |
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| author | Zi-Han Shen Tongjie Ye Baozhen Chen Congchao Wan Xiaolin Lu Ting-Hsu Chen Shuang Lin Jia-Xin Ye Liping Xie Yaw-Syan Fu |
| author_facet | Zi-Han Shen Tongjie Ye Baozhen Chen Congchao Wan Xiaolin Lu Ting-Hsu Chen Shuang Lin Jia-Xin Ye Liping Xie Yaw-Syan Fu |
| author_sort | Zi-Han Shen |
| collection | DOAJ |
| description | Abstract Hypertension is one of the most serious chronic diseases. This study will focus on the systemic antihypertensive mechanisms of 5,7-dihydroxyflavone from in silico simulations to in vivo validations. In-silico studies were applied by network pharmacology, molecular docking, and molecular dynamic simulation. Based on the information of network pharmacology, 5,7-dihydroxyflavone could act on several different blood pressure regulating pathways, molecular docking results confirmed it might direct binding on the active pocket of eNOS, and the average molecular distance between 5,7-dihydroxyflavone -eNOS is less than 0.4 Å by molecular dynamic simulation. The in vivo studies were carried by SHRs oral administrated with 10 mg/kg 5,7-dihydroxyflavone that could alleviate hypertensive symptoms within 30 min, but if SHRs pretreated with L-NAME (10 mg/kg, an eNOS inhibitor) can erase the anti-hypertensive effects of 5,7-dihydroxyflavone, but no affected by aminoguanidine pretreatment (100 mg/kg, the selective antagonist of iNOS). Furthermore, oral administration of 5,7-dihydroxyflavone does not affect the heart rate and pulse pressure difference in SHR rats. In conclusion, the effects of 5,7-dihydroxyflavone on blood pressure regulation may act on eNOS as an agonist to achieve its acute antihypertensive effects. These acute antihypertensive effects suggest that 5,7-dihydroxyflavone has the potential to be a candidate medication for urgently lowering blood pressure requirements without posing hypertensive risks. |
| format | Article |
| id | doaj-art-05335c5a9fb54459be51aea2ba3be06e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-05335c5a9fb54459be51aea2ba3be06e2025-01-05T12:14:50ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-024-84259-65,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive ratsZi-Han Shen0Tongjie Ye1Baozhen Chen2Congchao Wan3Xiaolin Lu4Ting-Hsu Chen5Shuang Lin6Jia-Xin Ye7Liping Xie8Yaw-Syan Fu9College of Clinical Medicine, Xiamen Medical CollegeCollege of Clinical Medicine, Xiamen Medical CollegeCollege of Pharmacy, Xiamen Medical CollegeCollege of Clinical Medicine, Xiamen Medical CollegeDepartment of Neurology, the Second Affiliated Hospital of Xiamen Medical CollegeGraduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan UniversityCollege of Clinical Medicine, Xiamen Medical CollegeCollege of Clinical Medicine, Xiamen Medical CollegeAnatomy Department, College of Basic Medical Science, Xiamen Medical CollegeAnatomy Department, College of Basic Medical Science, Xiamen Medical CollegeAbstract Hypertension is one of the most serious chronic diseases. This study will focus on the systemic antihypertensive mechanisms of 5,7-dihydroxyflavone from in silico simulations to in vivo validations. In-silico studies were applied by network pharmacology, molecular docking, and molecular dynamic simulation. Based on the information of network pharmacology, 5,7-dihydroxyflavone could act on several different blood pressure regulating pathways, molecular docking results confirmed it might direct binding on the active pocket of eNOS, and the average molecular distance between 5,7-dihydroxyflavone -eNOS is less than 0.4 Å by molecular dynamic simulation. The in vivo studies were carried by SHRs oral administrated with 10 mg/kg 5,7-dihydroxyflavone that could alleviate hypertensive symptoms within 30 min, but if SHRs pretreated with L-NAME (10 mg/kg, an eNOS inhibitor) can erase the anti-hypertensive effects of 5,7-dihydroxyflavone, but no affected by aminoguanidine pretreatment (100 mg/kg, the selective antagonist of iNOS). Furthermore, oral administration of 5,7-dihydroxyflavone does not affect the heart rate and pulse pressure difference in SHR rats. In conclusion, the effects of 5,7-dihydroxyflavone on blood pressure regulation may act on eNOS as an agonist to achieve its acute antihypertensive effects. These acute antihypertensive effects suggest that 5,7-dihydroxyflavone has the potential to be a candidate medication for urgently lowering blood pressure requirements without posing hypertensive risks.https://doi.org/10.1038/s41598-024-84259-6HypertensionMolecular dockingeNOSIn vivo |
| spellingShingle | Zi-Han Shen Tongjie Ye Baozhen Chen Congchao Wan Xiaolin Lu Ting-Hsu Chen Shuang Lin Jia-Xin Ye Liping Xie Yaw-Syan Fu 5,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive rats Scientific Reports Hypertension Molecular docking eNOS In vivo |
| title | 5,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive rats |
| title_full | 5,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive rats |
| title_fullStr | 5,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive rats |
| title_full_unstemmed | 5,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive rats |
| title_short | 5,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive rats |
| title_sort | 5 7 dihydroxyflavone acts on enos to achieve hypotensive effects in spontaneously hypertensive rats |
| topic | Hypertension Molecular docking eNOS In vivo |
| url | https://doi.org/10.1038/s41598-024-84259-6 |
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