Nymphaea pubescens Willd. extract and its flavonoid constituents vasodilate rat isolated pulmonary artery via NO-sGC-cGMP pathway

Q3 Pharmacology, Toxicology and Pharmaceutics

Phytomedicine Plus Pub Date : 2025-02-01 DOI:10.1016/j.phyplu.2025.100733

Teerapap Panklai , Prapapan Temkitthawon , Nungruthai Suphrom , Corine Girard , Perle Totoson , Kowit Hengphasatporn , Yasuteru Shigeta , Krongkarn Chootip , Kornkanok Ingkaninan

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Abstract

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 N^G-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.

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