Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathway
Background: Pulmonary arterial hypertension (PAH) is a progressive disorder indicated by elevated blood pressure in pulmonary artery (PA). PAH treatment focuses on inducing PA vasodilation by inhibiting phosphodiesterase 5 (PDE5), the enzyme prominently expressed in pulmonary vasculature. Our previo...
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031325000065 |
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| author | Teerapap Panklai Prapapan Temkitthawon Nungruthai Suphrom Corine Girard Perle Totoson Kowit Hengphasatporn Yasuteru Shigeta Krongkarn Chootip Kornkanok Ingkaninan |
| author_facet | Teerapap Panklai Prapapan Temkitthawon Nungruthai Suphrom Corine Girard Perle Totoson Kowit Hengphasatporn Yasuteru Shigeta Krongkarn Chootip Kornkanok Ingkaninan |
| author_sort | Teerapap Panklai |
| collection | DOAJ |
| description | Background: Pulmonary arterial hypertension (PAH) is a progressive disorder indicated by elevated blood pressure in pulmonary artery (PA). PAH treatment focuses on inducing PA vasodilation by inhibiting phosphodiesterase 5 (PDE5), the enzyme prominently expressed in pulmonary vasculature. Our previous research demonstrated that the extract (WLE) derived from the petals of the water lily (Nymphaea pubescens Willd.) and its flavonoid constituents, 3-methyl ether 3´-O-β-xylopyranoside (1), quercetin (2), and kaempferol (3), exhibited PDE5 inhibitory property, suggesting that WLE and its constituents may contribute to PA vasodilation. Methods: Dried N. pubescens petals were extracted with 95 % ethanol to provide the WLE. The vasorelaxant effects of the WLE and its flavonoid constituents were evaluated on rat PA and aorta using organ bath technique. The cytotoxicity of the WLE was also tested on the vascular smooth muscle cells (VSMCs) isolated from PA and aorta. Furthermore, a molecular docking study was performed to confirm the binding mode of flavonoid constituents to PDE5. Results: The WLE relaxed PA (EC50=4.96±0.81µg/ml) more than the aorta (EC50=27.50±7.61µg/ml, p < 0.001), suggesting its selectivity on the PA vs the aorta. PA vasorelaxation was reduced by endothelial removal or NG-nitro-l-arginine methyl ester (L-NAME), but was unaffected by indomethacin, apamin plus charybdotoxin, 4-aminopyridine (4-AP), glibenclamide, iberiotoxin, and BaCl2. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin -1- one (ODQ) reduced the relaxation induced by the WLE (p < 0.05). Sodium nitroprusside (SNP)-induced relaxation was enhanced by the WLE. WLE had no effect neither on extracellular Ca2+ influx through ROCCs/VOCCs nor intracellular Ca2+ release from the sarcoplasmic reticulum. PE-induced contraction via α1-receptor was also unaffected by WLE. Compounds 1–3 relaxed both PA and aorta rings with and without endothelium (EC50=26 - >100 µM). VSMCs incubated with the WLE for 1 hr showed no acute cytotoxicity. The binding of compounds 1–3 to PDE5 is slightly better than that of native PDE5 inhibitors. Conclusions: Both WLE and its flavonoids (1–3) vasodilated PA. The mechanism of WLE vascular action involved the endothelial nitric oxide (NO) pathway and stimulation of sGC, while showing no VSMC cytotoxicity. |
| format | Article |
| id | doaj-art-68e4b8a797fb4a69a4fb3aa3cf02f022 |
| institution | Kabale University |
| issn | 2667-0313 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | Phytomedicine Plus |
| spelling | doaj-art-68e4b8a797fb4a69a4fb3aa3cf02f0222025-02-10T04:35:20ZengElsevierPhytomedicine Plus2667-03132025-02-0151100733Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathwayTeerapap Panklai0Prapapan Temkitthawon1Nungruthai Suphrom2Corine Girard3Perle Totoson4Kowit Hengphasatporn5Yasuteru Shigeta6Krongkarn Chootip7Kornkanok Ingkaninan8Center of Excellence in Cannabis Research, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand; Université de Franche-Comté, PEPITE, Besançon 25000, FranceCenter of Excellence in Cannabis Research, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, ThailandDepartment of Chemistry, Faculty of Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, ThailandUniversité de Franche-Comté, PEPITE, Besançon 25000, FranceUniversité de Franche-Comté, PEPITE, Besançon 25000, FranceCenter for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, JapanCenter for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, JapanDepartment of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand; Centre of Excellence in Medical Biotechnology, Naresuan University, Phitsanulok 65000, Thailand; Corresponding authors.Center of Excellence in Cannabis Research, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand; Corresponding authors.Background: Pulmonary arterial hypertension (PAH) is a progressive disorder indicated by elevated blood pressure in pulmonary artery (PA). PAH treatment focuses on inducing PA vasodilation by inhibiting phosphodiesterase 5 (PDE5), the enzyme prominently expressed in pulmonary vasculature. Our previous research demonstrated that the extract (WLE) derived from the petals of the water lily (Nymphaea pubescens Willd.) and its flavonoid constituents, 3-methyl ether 3´-O-β-xylopyranoside (1), quercetin (2), and kaempferol (3), exhibited PDE5 inhibitory property, suggesting that WLE and its constituents may contribute to PA vasodilation. Methods: Dried N. pubescens petals were extracted with 95 % ethanol to provide the WLE. The vasorelaxant effects of the WLE and its flavonoid constituents were evaluated on rat PA and aorta using organ bath technique. The cytotoxicity of the WLE was also tested on the vascular smooth muscle cells (VSMCs) isolated from PA and aorta. Furthermore, a molecular docking study was performed to confirm the binding mode of flavonoid constituents to PDE5. Results: The WLE relaxed PA (EC50=4.96±0.81µg/ml) more than the aorta (EC50=27.50±7.61µg/ml, p < 0.001), suggesting its selectivity on the PA vs the aorta. PA vasorelaxation was reduced by endothelial removal or NG-nitro-l-arginine methyl ester (L-NAME), but was unaffected by indomethacin, apamin plus charybdotoxin, 4-aminopyridine (4-AP), glibenclamide, iberiotoxin, and BaCl2. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin -1- one (ODQ) reduced the relaxation induced by the WLE (p < 0.05). Sodium nitroprusside (SNP)-induced relaxation was enhanced by the WLE. WLE had no effect neither on extracellular Ca2+ influx through ROCCs/VOCCs nor intracellular Ca2+ release from the sarcoplasmic reticulum. PE-induced contraction via α1-receptor was also unaffected by WLE. Compounds 1–3 relaxed both PA and aorta rings with and without endothelium (EC50=26 - >100 µM). VSMCs incubated with the WLE for 1 hr showed no acute cytotoxicity. The binding of compounds 1–3 to PDE5 is slightly better than that of native PDE5 inhibitors. Conclusions: Both WLE and its flavonoids (1–3) vasodilated PA. The mechanism of WLE vascular action involved the endothelial nitric oxide (NO) pathway and stimulation of sGC, while showing no VSMC cytotoxicity.http://www.sciencedirect.com/science/article/pii/S2667031325000065Nymphaea pubescensPulmonary arteryVasorelaxationPulmonary arterial hypertensionCytotoxicityFlavonoids |
| spellingShingle | Teerapap Panklai Prapapan Temkitthawon Nungruthai Suphrom Corine Girard Perle Totoson Kowit Hengphasatporn Yasuteru Shigeta Krongkarn Chootip Kornkanok Ingkaninan Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathway Phytomedicine Plus Nymphaea pubescens Pulmonary artery Vasorelaxation Pulmonary arterial hypertension Cytotoxicity Flavonoids |
| title | Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathway |
| title_full | Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathway |
| title_fullStr | Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathway |
| title_full_unstemmed | Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathway |
| title_short | Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathway |
| title_sort | nymphaea pubescens willd extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via no sgc cgmp pathway |
| topic | Nymphaea pubescens Pulmonary artery Vasorelaxation Pulmonary arterial hypertension Cytotoxicity Flavonoids |
| url | http://www.sciencedirect.com/science/article/pii/S2667031325000065 |
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