OBJECTIVE: To study hesperetin-induced vasorelaxation after depolarizing contraction in human umbilical veins (HUVs) to elucidate the role of L-type Ca²⁺ channel (LTCC) and related signaling pathway. METHODS: Isometric tension recording was performed in HUV rings pre-contracted with K⁺. Hesperetin relaxing mechanism was investigated using a LTCC opener (BayK8644) and blockers of cyclic nucleotides and phosphodiesterases (PDEs). Whole-cell patch-clamping in A7r5 cells, a rat vascular smooth muscle cell line, was performed to study the effect of hesperetin on LTCC current. RESULTS: After depolarizing precontraction, hesperetin induced HUV relaxation concentration-dependently and endothelium-independently; 1 mmol/L hesperetin reduced denuded HUV ring tension by 68.7% ± 4.3% compared to matching vehicle, osmolality, and time controls (P<0.0001). Importantly, hesperetin competitively inhibited BayK8644-induced contraction, shifting the half maximal effective concentration of BayK8644 response from 1.08 nmol/L [95% confidence interval (CI) 0.49-2.40] in vehicle control to 11.30 nmol/L (95% CI 5.45-23.41) in hesperetin (P=0.0001). Moreover, hesperetin elicited further vasorelaxation in denuded HUV rings pretreated with inhibitors of soluble guanylyl cyclase, adenylyl cyclase, PDE3, PDE4, and PDE5 (P<0.01), while rings pretreated with PDE1 inhibitors could not be relaxed by hesperetin (P>0.05). However, simultaneously applying inhibitors of soluble guanylyl cyclase and adenylyl cyclase could not inhibit hesperetin's effect (P>0.05). In whole-cell patch-clamping, hesperetin rapidly decreased LTCC current in A7r5 cells to 66.7% ± 5.8% (P=0.0104). CONCLUSIONS Hesperetin diminishes depolarizing contraction of human vascular smooth muscle through inhibition of LTCC, and not cyclic nucleotides nor PDEs. Our evidence supports direct LTCC interaction and provides additional basis for the use of hesperetin and its precursor hesperidin as vasodilators and may lead to future vasodilator drug development as a treatment alternative for cardiovascular diseases.
Hesperidin/pharmacology* ; Humans ; Calcium Channels, L-Type/metabolism* ; Umbilical Veins/physiology* ; Muscle Contraction/drug effects* ; Animals ; Rats ; Calcium Channel Blockers/pharmacology* ; Vasodilation/drug effects* ; Muscle Relaxation/drug effects*

Lotus( Nelumbo nucifera) is a traditional medicinal plant,and nowadays it is regarded both as medicine and food. It is widespread across China and rich in natural resources. Almost every part of N. nucifera could be used for medical or edible purpose,including seeds( Lianzi),black ripe fruits( Shilianzi),seed coats( Lianyi),green embryos of mature seed( Lianzixin),flowers( Lianhua),stamens( Lianxu),receptacles( Lianfang),leaves( Heye),leaf or flower stalks( Hegeng),leaf bases( Heyedi),rhizomes( Ou) and rhizome nodes( Oujie). Therefore,this plant is praised as a commercial crop with great economic values. Isoquinoline type alkaloids are the main chemical components of lotus. Smooth muscles usually exist in the digestive tract,respiratory tract and vascular,urinary,reproductive and other human systems. Dysfunction of smooth muscle contraction will induce many diseases including hypertension,asthma and gastrointestinal disorder,etc.,and most of current therapeutic strategies rely on relaxation of smooth muscle by drugs.Previous studies have shown that alkaloids of lotus have strong relaxation activity on smooth muscle. The present paper reviews phytochemistry and smooth muscle relaxation activity of 59 isoquinoline alkaloids from N. nucifera through accessing CNKI,PubMed and multiple databases for biomedical sciences.
Alkaloids/pharmacology* ; China ; Humans ; Isoquinolines/pharmacology* ; Muscle Relaxation ; Muscle, Smooth/drug effects* ; Nelumbo/chemistry* ; Phytochemicals/pharmacology* ; Plant Extracts

OBJECTIVETo investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.

METHODSThe ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats.

RESULTSPreconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca sensitive-K channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently.

CONCLUSIONBAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca sensitive-K (BK and IK) channels in the corpus cavernosum.

Animals ; Area Under Curve ; Berberis ; chemistry ; Blood Pressure ; drug effects ; Cyclic GMP ; metabolism ; Epoprostenol ; pharmacology ; In Vitro Techniques ; Indomethacin ; pharmacology ; Male ; Models, Biological ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Penile Erection ; drug effects ; Phenylephrine ; pharmacology ; Plant Extracts ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Pressure ; Rabbits

OBJECTIVETo examine the relaxant effects of hydro-ethanolic, macerated aqueous (MA) and lipidfree macerated aqueous (LFMA) extract of Tymus vulgaris on tracheal chains of guinea pigs.

METHODSThe relaxant effects of five cumulative concentrations of each extract (0.4, 0.8, 1.2, 1.6 and 2.0 g/100 mL) were compared with saline as negative control and five cumulative concentrations of theophylline (0.1, 0.2, 0.4, 0.6 and 0.8 mmol/L) on precontracted tracheal smooth muscle of guinea pig with 60 mmol/L KCl (group 1) and 10 µmol/L methacholine (group 2, n=6 for each group).

RESULTSIn group 1 all concentrations of theophylline, three higher concentrations of hydro-ethanolic, two concentrations of LFMA and last concentration of MA extracts showed significant relaxant effects compared with that of saline (P<0.05 or P<0.01). Two lower concentrations of LFMA and all concentrations of MA except higher one caused contraction compared with saline (P<0.05 or 0.01). In group 2 experiments, all concentrations of theophylline, hydro-ethanolic, MA and LFMA extracts showed significant relaxant effects compared to that of saline (P<0.05 or P<0.01). In both groups, the relaxant effect of all concentrations of hydro-ethanolic extract were significantly higher than most concentrations of others (P<0.05 or P<0.01). The relaxant effect of different concentrations of three extracts were significantly greater in group 2 compared with group 1 experiments (all P<0.01). There were significantly positive correlations between the relaxant effects and concentrations for theophylline and all extracts in both groups (P<0.05 or P<0.01).

CONCLUSIONHydro-ethanolic extract has a potent weaker relaxant effect for other extracts from Tymus vulgaris on tracheal chains of guinea pigs.

Animals ; Bronchodilator Agents ; pharmacology ; Guinea Pigs ; In Vitro Techniques ; Lamiaceae ; chemistry ; Lipids ; chemistry ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Plant Extracts ; pharmacology ; Solubility ; Solutions ; Theophylline ; Trachea ; physiology ; Water ; chemistry

AIM: Trichosanthes dioica Roxb. (Cucurbitaceae), commonly known as pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. Traditionally, this plant has been used in India for several medicinal purposes. The present study aimed to evaluate certain neuropharmacological properties of the hydroalcoholic extract of T. dioica root (TDA) in experimental animal models. METHODS: TDA (at 100 and 200 mg·kg(-1) body weight, p.o.) was evaluated for anti-nociceptive activity by the acetic acid-induced writhing and tail flick methods. Locomotor depressant activity was measured by means of an actophotometer. Skeletal muscle relaxant effects were evaluated by using a rota-rod apparatus, and the sedative potentiating property by a phenobarbitone-induced sleep potentiation study. RESULTS: The results of the present study revealed significant (P < 0.001) and dose dependent anti-nociceptive, locomotor depressant, muscle relaxant, and sedative potentiating effects of TDA, demonstrating its depressant action on the central nervous system (CNS). CONCLUSION From the present study, it can be concluded that T. dioica root possessed prominent anti-nociceptive, as well as depressant, action on the CNS, as manifested by these important neuropharmacological properties in mice.
Analgesics ; administration & dosage ; Animals ; Central Nervous System Diseases ; drug therapy ; physiopathology ; Humans ; India ; Male ; Mice ; Muscle Relaxants, Central ; administration & dosage ; Muscle Relaxation ; drug effects ; Neuropharmacology ; Plant Extracts ; administration & dosage ; Plant Roots ; chemistry ; Trichosanthes ; chemistry

The study on the Rauvolfia verticillata (Lour.) Baill., which belongs to Apocynaceae, was carried out to look for its chemical constituents and pharmacological activity. The isolation and purification were performed by chromatography on silica gel, Sephadex LH-20 and ODS (octadecyl silane) open column. The structures of obtained compounds were elucidated on the basis of physicochemical properties and spectral analysis. Three indole alkaloids and one acridone alkaloid were isolated from chloroform layer extract and identified as ajmalicine B (1), sandwicine (2), raunescine (3) and 7-hydroxynoracronycine (4) separately. Ajmalicine B (1) is a new compound belonging to indole alkaloid. Compound 4 as an acridone alkaloid was a new type compound isolated from Rauvolfia genus for the first time. We also did some biological activity research on the new type compound (4) to explore other pharmacological activities in addition to antihypertensive activity.
Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; pharmacology ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; HL-60 Cells ; Humans ; Indole Alkaloids ; chemistry ; isolation & purification ; pharmacology ; Inhibitory Concentration 50 ; Intestine, Small ; physiology ; MCF-7 Cells ; Molecular Structure ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; physiology ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Rabbits ; Rauwolfia ; chemistry

Human rhinoviruses (HRVs) are the causative pathogens in more than half of viral upper respiratory tract infections. Currently, no antiviral agents that are active against HRVs are available for clinical use. Because only higher primates are susceptible to HRVs, the screening of new drug is most commonly based on the cell line model. In this study, isolated rabbit airway smooth muscles (ASM) tissue model has been established, and the airway responsiveness with different treatment has been examined. Relative to control tissues, the maximal constrictor (Tmax) response to ACh increased significantly 150% in ASM inoculated with HRV, and relaxation to isoproterenol has been attenuated to 63%. And the abnormal responsiveness can be inhibited in presence of pretreatment with several new compounds which have been exhibited effective anti-HRV activity on cell lines. The results demonstrate that the established ASM model will be applied to screening the anti-HRVs drugs.
Acetylcholine ; pharmacology ; Animals ; Antiviral Agents ; pharmacology ; Cytopathogenic Effect, Viral ; drug effects ; HeLa Cells ; Humans ; Isoproterenol ; pharmacology ; Muscle Contraction ; drug effects ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiopathology ; virology ; Piperidines ; pharmacology ; Pyridazines ; pharmacology ; Rabbits ; Rhinovirus ; Trachea ; drug effects ; physiopathology ; virology

OBJECTIVETo determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects.

METHODSPhenylephrine or potassium chloride concentration-dependent relaxation response of aortic smooth muscles to matrine was studied in the precontracted guinea pigs.

RESULTSMatrine (1 x 10(-4) mol/L -3.3 x 10(3) mol/L) relaxed the endothelium-denuded aortic rings pre-contracted sub-maximally with phenylephrine, in a concentration-dependent manner, and its pre-incubation (3.3 x 10(-3) mol/L) produced a significant rightward shift in the phenylephrine dose-response curve, but had no effects on the potassium chloride-induced contraction. The anti-contractile effect of matrine was not reduced by the highly selective ATP-dependent K+ channel blocker glibenclamide (10(-5) mol/L), either by the non-selective K+ channel blocker tetraethylammonium (10(-3) mol/L), or by the beta-antagonist propranolol (10(-5) mol/L). In either "normal" or "Ca(2+)-free" bathing medium, the phenylephrine-induced contraction was attenuated by matrine (3.3 x 10(-3) mol/L), indicating that the vasorelaxation was due to inhibition of intracellular and extracellular Ca2+ mobilization.

CONCLUSIONMatrine inhibits phenylephrine-induced contractions by inhibiting activation of alpha-adrenoceptor and interfering with the release of intracellular Ca2+ and the influx of extracellular Ca2+.

Alkaloids ; chemistry ; pharmacology ; Animals ; Aorta ; drug effects ; physiology ; Calcium ; pharmacology ; Culture Media ; pharmacology ; Dose-Response Relationship, Drug ; Glyburide ; pharmacology ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Muscle Relaxation ; drug effects ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Phenylephrine ; pharmacology ; Potassium Chloride ; pharmacology ; Propranolol ; pharmacology ; Quinolizines ; chemistry ; pharmacology ; Tetraethylammonium ; pharmacology

OBJECTIVETo investigate the vasorelaxant effect of taurine (Tau) in rat aortic rings and the mechanism.

METHODThe isolated thoracic aortic rings of male Wistar rats were mounted on the organ bath. The effect of Tau 10, 20, 40, 80 mmol x L(-1) on the rings with endothelium intact or endothelium denuded precontracted by the phenylephrine (1 micromol x L(-1)) or KCl (60 mmol x L(-1)), and the effect of Tau on the vessel reaction induced by various drugs were recorded with biological signal analytical system.

RESULTTaurine completely relaxed the contractions induced by KCl and phenylephrine in a concentration-dependent manner in endothelium-intact and endothelium-denuded rat aorta. Taurine attenuated the contraction to PE both in the absence and presence of calcium, but had no significant effect on the contraction induced by caffeine. The relaxant effect of taurine was significantly inhibited by pretreatment of endothelium-denuded aorta with potassium channel antagonists glibenclamide and tetraethylamine but not by BaCl2 or 4-aminopyridine.

CONCLUSIONTaurine induces an endothelium-independent relaxation in rat aortic rings. The mechanisms may involve the reduction in Ca2+-influx and Ca2+-release and the participation of the potassium channels (KATP and KCa, but not Kir or KV).

Animals ; Aorta ; drug effects ; physiology ; Endothelium, Vascular ; drug effects ; physiology ; Male ; Models, Animal ; Muscle Relaxation ; drug effects ; Rats ; Rats, Wistar ; Taurine ; pharmacology ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

Acetylcholine ; metabolism ; physiology ; Animals ; Cholinergic Agonists ; pharmacology ; Male ; Muscle Contraction ; drug effects ; physiology ; Muscle Relaxation ; drug effects ; physiology ; Muscle, Smooth ; drug effects ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Receptors, Cholinergic ; physiology ; Synaptic Transmission ; drug effects ; Urinary Bladder ; drug effects ; innervation ; physiopathology