ArticleNaunyn-Schmiedeberg's archives of pharmacology2004
Comparative study of the vasorelaxant activity, superoxide-scavenging ability and cyclic nucleotide phosphodiesterase-inhibitory effects of hesperetin and hesperidin.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 71 citations in OpenAlex.
- Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome.The Journal of clinical endocrinology and metabolism · 2011Trial
- Protective Role of Hesperidin Against Deltamethrin-Induced Cardiovascular Structural Damage: Involvement of Caspase-3-Driven Apoptosis and Fibrosis Suppression in Rats.Journal of cardiovascular development and disease · 2026Article
- Hesperetin Relaxes Depolarizing Contraction in Human Umbilical Vein by Inhibiting L-Type CaChinese journal of integrative medicine · 2025Article
- Hesperidin facilitating gastrointestinal motility by "Gut-brain axis" and "SCF/C-Kit signaling pathways".Poultry science · 2024Article
- Research progress on the mechanism of action of hesperetin in cerebral ischemia: a narrative review.Annals of translational medicine · 2022Review
- An ethnopharmacological review on the therapeutical properties of flavonoids and their mechanisms of actions: A comprehensive review based on up to date knowledge.Toxicology reports · 2022Review
- A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Review of Natural Resources With Vasodilation: Traditional Medicinal Plants, Natural Products, and Their Mechanism and Clinical Efficacy.Frontiers in pharmacology · 2021Review
- Hesperetin improves diabetic coronary arterial vasomotor responsiveness by upregulating myocyte voltage-gated KExperimental and therapeutic medicine · 2020Article
- Hesperidin depolarizes the pacemaker potentials through 5-HTAnimal cells and systems · 2020Article
- Hesperidin alleviates rat postoperative ileus through anti-inflammation and stimulation of Ca(2+)-dependent myosin phosphorylation.Acta pharmacologica Sinica · 2016Article
- Vasodilator compounds derived from plants and their mechanisms of action.Molecules (Basel, Switzerland) · 2013Review
- Endothelium-independent and endothelium-dependent vasorelaxation by a dichloromethane fraction from Anogeissus Leiocarpus (DC) Guill. Et Perr. (Combretaceae): possible involvement of cyclic nucleotide phosphodiesterase inhibition.African journal of traditional, complementary, and alternative medicines : AJTCAM · 2013Article
- β-Adrenergic cAMP signals are predominantly regulated by phosphodiesterase type 4 in cultured adult rat aortic smooth muscle cells.PloS one · 2012Article
- PDEs1-5 activity and expression in tissues of cirrhotic rats reveal a role for aortic PDE3 in NO desensitization.International journal of experimental pathology · 2009Article
- Exploring the effect of Hesperetin-HSPC complex--a novel drug delivery system on the in vitro release, therapeutic efficacy and pharmacokinetics.AAPS PharmSciTech · 2009Article
- Study of the mechanisms involved in the vasorelaxation induced by (-)-epigallocatechin-3-gallate in rat aorta.British journal of pharmacology · 2006Article
- The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives.Cardiovascular journal of AfricaReview
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study investigated the vasorelaxant activity, superoxide radicals (O2(*-))-scavenging capacity and cyclic nucleotide phosphodiesterase (PDE)-inhibitory effects of hesperidin and hesperetin, two flavonoids mainly isolated from citrus fruits. Hesperetin concentration-dependently relaxed the isometric contractions induced by noradrenaline (NA, 1 microM) or by a high extracellular KCl concentration (60 mM) in intact rat isolated thoracic aorta rings. However, hesperetin (10 microM-0.3 mM) did not affect the contractile response induced by okadaic acid (OA, 1 microM). Mechanical removal of endothelium and/or pretreatment of aorta rings with glibenclamide (GB, 10 microM), tetraethylammonium (TEA, 2 mM) or nifedipine (0.1 microM) did not significantly modify the vasorelaxant effects of this flavonoid. Hesperetin (10 microM-0.1 mM) did not affect the basal uptake of (45)Ca(2+) but decreased the influx of (45)Ca(2+) induced by NA and KCl in endothelium-containing and endothelium-denuded rat aorta. Hesperetin (10 microM-0.1 mM) did not scavenge O2(*-) generated by the phenazine methosulfate (PMS)-reduced beta-nicotinamide adenine dinucleotide (NADH) system. Hesperetin (0.1 mM) significantly reversed the inhibitory effects of NA (1 microM) and high KCl (60 mM) on cyclic nucleotide (cAMP and cGMP) production in cultured rat aortic myocytes. Hesperetin preferentially inhibited calmodulin (CaM)-activated PDE1 and PDE4 isolated from bovine aorta with IC(50) values of about 74 microM and 70 microM respectively. In contrast, the 7-rhamnoglucoside of hesperetin, hesperidin (10 microM-0.1 mM), was inactive in practically all experiments, although it inhibited basal and cGMP-activated PDE2 isolated from platelets (IC(50) values of 32+/-4 microM and 137+/-34 microM respectively). These results suggest that the vasorelaxant effects of hesperetin are basically due to the inhibition of PDE1 and PDE4 activities.
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