Vasorelaxant Activity Research Articles

Salvia aucheri Exhibits Antihypertensive Activity in Hypertensive Rats.

The present work aimed to assess the antihypertensive activity of Salvia aucheri. Salvia aucheri (S. aucheri) is an aromatic and medicinal herb belonging to the Lamiaceae family. In Morocco, this plant is locally used for used to treat stomach, digestive disorders, rheumatism, and hypertension. Nevertheless, the effect of Salvia aucheri on hypertension has not yet been studied. The objective of this investigation was to evaluate the beneficial effect of the aqueous extract of S. aucheri leaves on arterial blood pressure, systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) in normotensive and hypertensive rats. In addition, the effect of the aqueous extract of S. aucheri leaves on vasodilatation was assessed in isolated rat aortic rings with functional endothelium precontracted with epinephrine EP or KCl. The aqueous extract of the aerial parts of S. aucheri (AESA) was obtained, and its antihypertensive ability was pharmacologically investigated in L-NAME hypertensive and normotensive rats. The rats received AESA orally at two selected doses of 100 and 140 mg/kg for six hours (acute experiment) and seven days (sub-chronic). Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. Moreover, the vasorelaxant activity of AESA was performed in thoracic aortic ring rats. In addition, the mechanisms of action involved in the vasorelaxant effect were studied. The results indicated that AESA significantly reduced the systolic, diastolic, and mean arterial blood pressure in hypertensive rats over both single and repeated oral administration. However, AESA did not change the blood pressure parameters in normotensive rats. Concerning the results of vasorelaxant activity, the results showed that AESA was able to provoke potent vasorelaxant ability, which seems to be mediated through direct nitric oxide (NO) and NO-cyclic guanosine monophosphate pathways. The study elucidates the beneficial action of AESA as an antihypertensive and vasorelaxant agent.

New insights on mode of action of vasorelaxant activity of simvastatin.

Simvastatin is a semisynthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and is used extensively to treat atherosclerotic cardiovascular disease. Apart from the lipid-lowering effect, simvastatin has been documented to offer impressive vasorelaxant activity. However, the mechanism associated with this vasorelaxant activity has yet not been substantially explored. Thus, the present study has aimed to elucidate the mechanism(s) associated with simvastatin-induced vasorelaxation using an established rat aortic ring model. The results from the study depicted that simvastatin caused significant relaxation in aortic rings pre-contracted with phenylephrine and potassium chloride (KCl). The vasorelaxant effect of simvastatin was attenuated by methylene blue (sGC-dependent cyclic guanosine monophosphate (cGMP) inhibitor), NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor), 4-aminopyridine (Kv blocker), glibenclamide (KATP blocker), and barium chloride (Kir blocker). In addition, the vasorelaxant effect of simvastatin was slightly reduced by PD123319 (angiotensin II type 2 receptor (AT2R) antagonist). However, indomethacin (COX inhibitor), 1H-[1,2,4]Ox adiazolol [4,3-α]quinoxalin-1-one (ODQ; selective soluble guanylate cyclase (sGC) inhibitor), losartan (angiotensin II type 1 receptor (AT1R) antagonist), atropine (muscarinic receptor blocker), and tetraethyl ammonium (TEA; KCa blocker) did not affect the vasorelaxant effect of simvastatin. Furthermore, simvastatin was found to attenuate the release of calcium (Ca2+) from intracellular stores in the presence of ruthenium red (ryanodine receptor, RyR inhibitor) and extracellular stores via nifedipine (voltage-operated Ca2+ channels, VOCC blocker) and SK&F96365 (receptor-operated Ca2+ channel, ROCC blocker). Thus, it can be concluded that the vasorelaxant effect of simvastatin involves NO/cGMP pathways, AT2R receptors, Ca2+ channels, and K+ channels.

Antihypertrophic Effect of Menthol from Mentha x Piperita Concerning Cardiac Hypertrophy: A Review

Background: The abnormal enlargement or thickening of the heart muscle leads to diminishment of ventricular wall tension which helps to keep up the outstanding task at hand in terms of capacity and effectiveness. There are two kinds of hypertrophy: physiological and pathological. Initially, what evolves as an adaptive reaction, advances to heart failure. Different cellular signaling pathways control each type of hypertrophy. Peppermint - Mentha x piperita, a hybrid of Mentha spicata and Mentha aquatica belongs to the family of Lamiaceae. The peppermint oil has high menthol content and has many useful targets in cardiovascular disorders, such as hypertension, coronary heart disease, etc., Objective: The objective of this review article is to investigate the antihypertrophic activity of Mentha x piperita which is not yet established Methods: For manuscript preparation, we had used all accessible international databases, traditional books (Regular books in English), and electronic resources (Google Scholar, PubMed, Science Direct, Springer, Wiley, etc.,), unpublished data (thesis, R&D reports, and dissertations). Results: Menthol may activate Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRMP8) channels resulting in increased cytosolic calcium concentration and vasorelaxation activity. Menthol is known to stimulate the elevation of TRPM8 protein in the endothelium, Vascular Smooth Muscle (VSM), and vascular afferent nerve strands, while obstructing VSM L-type Calcium Channels (LCC), contributing to both the cardiovascular and vasoactive properties of peppermint. In vivo experiments proved that glucagon plays a significant role in the preventive effect of menthol (as TRPM8 modulator) against a high-fat diet (HFD) induced weight gain and related complications. Conclusion: Due to the efficacy of Menthol (Mentha x piperita) in its cardioprotective properties, understanding the actual mechanisms related to the efficacy of Menthol on CVD can be the subject of future studies.

Antioxidant and Vasorelaxant Properties of Phaseolus vulgaris Linn (Fabaceae) Immature Pods Extract on the Thoracic Aorta of NMRI Mice

Introduction: Oxidative stress, through the increased bioavailability of reactive oxygen species (ROS), is a major cause of hypertension. The resulting endothelial remodeling promotes the production of vasoconstrictor substances leading to an increase in blood pressure. This study aimed to evaluate the antioxidant and vasorelaxant properties of the decoction (PAD), ethyl acetate (EAP), and residual aqueous (ARP) fractions of immature Phaseolus vulgaris pods on NMRI mice thoracic aorta rings. Methods: Phytochemical screening was performed by high-performance thin-layer chromatography. Folin-Ciocalteu and aluminum trichloride colorimetric methods were used to quantify total polyphenol compounds (TPC) and total flavonoids (TFC), respectively. Antioxidant activities of the extracts were determined by 2,29-azinobis-3-ethylbenzothiazoline-6-sulfonic (ABTS●), 2,2-Diphenyl-1-picrylhydrazyl (DPPH●), and ferric ion (FRAP) radical reduction methods. The DMT 620M ADInstruments myograph technique was used to evaluate the ex-vivo vasodilatory effects of Phaseolus vulgaris extracts on aortic rings. Results: Chromatographic fingerprints showed the presence of flavonoids, coumarins, tannins, steroids, triterpenes, and saponins in the extracts studied. The TPC (61.07±0.04 mgGAE/g) and TFC (6.16±0.03 mgQE/g) of EAP were statistically significant compared to that of PAD and ARP (p<0.001). The antioxidant power of Trolox was statistically significant compared to all studied extracts (p<0.05). It should be noted that among these extracts, EAP showed the better antiradical capacities for ABTS (IC50=71.87±0.30 µg/mL) and DPPH (IC50=9.93±0.00 µg/mL). However, for FRAP activity, it was the PAD extract (T=170.68±0.11 µgAAE/g) that obtained the best score. In terms of vasorelaxant activity, all extracts induced concentration-dependent relaxation of aortic rings precontracted with U46619. Pharmacodynamic parameters were significantly in favor of EAP [EAP(E+)=(Emax=100.06±0.00%; pD2=1.24±0.01) and EAP(E-)=(Emax=101.01±0.00%; pD2=0.84±0.02)] followed by PAD and then ARP. Conclusion: Phaseolus vulgaris immature pod extracts possess concentration-dependent vasorelaxant effects on isolated mouse aorta. These preliminaries results were scientific evidence to support the use of this plant in traditional and complementary medicine for the treatment of hypertension.

Optimization of Reaction Condition for Synthesis of 4-Methoxychalcone from Ethyl p-methoxycinnamate

Ethyl p-methoxycinnamate (1) is the main secondary metabolite found in Kaempferia galanga Linn and has various interesting pharmacological activities, including anti-inflammatory, sedative, vasorelaxant, and antiangiogenic activities. This study aimed to optimize the conditions for the conversion of 1 to 4-methoxychalcone (2) using a conventional synthetic reaction. The conversion was initiated by the hydrolysis of 1 to p-methoxycinnamic acid (3) and 3 to 4-methoxybenzaldehyde (4), and continued with the Claisen-Schmidt reaction of 4 with acetophenone (5). The temperature (room temperature and 45 °C) and ratio of 4 to 5 (1:1 and 1:2) were varied to determine the optimal conditions for the reaction. The results suggested that the reaction of 4 with 5 gave the best yield (42.1 %) when conducted at room temperature in a ratio of 4 to 5 (1:1). The structure of the reaction product was elucidated by spectroscopic analysis and compared with previously published data

Ethnobotanical Survey and Pharmacological Screening of Medicinal Plants Used as Antihypertensive in Sefrou Province (Middle-North of Morocco): Benefits and Challenges

Herbal medicine was used since the old time in the treatment of different types of diseases in Sefrou province, Morocco. However, few studies have been carried out to identify local medicinal flora and to scientifically document the knowledge of the traditional use of these medicinal plants by the population. This study aims to investigate the medicinal plants in Sefrou province, record their usage in folk medicine by the population and evaluate the hypotensive effect of selected plants using in vitro vascular activity. For that, an ethnobotanical survey was conducted among the Arabs and Amazighs population of Sefrou province from January 2017 to December 2018. The survey was conducted through oral interviews with a structured questionnaire. It covered those who knew and/or used plants for medicinal purposes, retailers, and wholesalers, and also included ecological repartition as well as the mode of administration. Then we selected some plants to evaluate the antihypertensive activity based on the in vitro bioassay. A total of 134 medicinal plants belonging to 52 families were identified; 61% are wild species, 49 (36%) are cultivated and 4 (3%) are cultivated as well as spontaneous. Medicinal plants used in Sefrou folk medicine have been investigated for their antihypertensive activity. They were selected based on their usage as cardiotonic, diuretics, and other uses related to the symptoms of hypertension. Most of the plants tested in this study were found to be more sensitive to relaxing contractions induced by noradrenaline. Out of 32 species examined, 14 (44%) showed more than 50% inhibition in isolated rat aortic rings, the vasorelaxant activity of these plants used for the screening was mostly inhibited by pre-treatment with N-ω-nitro-L-arginine (L-NOArg). The plants inventoried are alleged to be active against 104 therapeutic indications. Nine common symptoms are widely treated in indigenous pharmacopeia: gastrointestinal (19 plants), renal (27 plants), broncho-pulmonary system (7 plants), skin (13 species), diabetes (12 plants), cardiovascular (13 plants), eye, ear, nose, teeth, and throat diseases (5 plants); gynecological disorders (6 plants); rheumatism and gnawing pain (11 plants). 14% (19 species) of the plant inventoried are traded on a large scale and scope and more than 90 percent of the medicinal plants purchased from Sefrou go to big cities for export. The expansion of unregulated trade and commercial use of medicinal and aromatic plants poses a major threat to biodiversity in the region. Overall, people in Sefrou hold rich knowledge of herbal medicine. The vasorelaxant activity proved for the documented plants will provide a basis for other preclinical and clinical investigations.

Influence of nitro ruthenium isomerization on photochemically induced nitric oxide release: Vasorelaxant activities

We have synthesized cis-[Ru(bpy)2(NO2-κN)Ln-](n-1) and cis-[Ru(bpy)2(NO2-κO)L n-](n-1) (bpy = 2,2′-bipyridine; k = indication of the coordinated center to Ruthenium; L = pyridine type ligand) by reacting cis-[Ru(bpy)2(H2O)Ln-](n-2) with sodium nitrite or conducting basic cis-[Ru(bpy)2NO(Ln-)](n-3) hydrolysis. Photolysis at the metal-ligand charge transfer band (MLCT) of the isomers yielded nitric oxide (NO) as determined by NO measurement. The NO photorelease rates obtained upon 447 nm laser irradiation of the ruthenium complexes showed that cis-[Ru(bpy)2(NO2-κO)Ln-](n-1) released NO three times faster than cis-[Ru(bpy)2(NO2-κN)Ln-](n-1). We investigated endothelium-dependent vasodilation induced by cis-[Ru(bpy)2(4-pic)(NO2-κN)]+ and cis-[Ru(bpy)2(4-pic)(NO2-κO)]+ (4-pic = 4-picoline) in isolated 3 mm aortic rings precontracted with L-phenylephrine. Maximum vasodilation was achieved under 447 nm laser irradiation of 0.5 μMol.L−1 ruthenium complexes for 100 s.

Antihypertensive Activity of Prunus armeniaca in Hypertensive Rats.

The goal of this work was to evaluate the antihypertensive activity of Prunus armeniaca. Prunus armeniaca is known for its beneficial medicinal properties. This study aimed to evaluate the effect of the aqueous extract of Prunus armeniaca L. (P. armeniaca) leaves (PAAE) on arterial blood pressure in normotensive and hypertensive rats. In the in vivo examination, N-omega-Nitro-L-arginine methyl ester hydrochloride( L-NAME)-induced hypertensive and normotensive rats received PAAE (160 and 100 mg/kg) orally for the acute experiment spanning 6 hours and for seven days for the subchronic treatment; their blood pressure parameters were also evaluated. In the in vitro experiment, isolated intact thoracic aortic rings were precontracted with KCl (80 mM) and epinephrine (EP) (10 μM), and vascular dilatation was assessed. PAAE lowered blood pressure parameters in L-NAME-induced hypertensive without affecting normotensive rats following oral administration, suggesting that PAAE possesses an antihypertensive effect. In addition, PAAE (0.25-1 mg/mL) revealed a vasorelaxant effect in thoracic aortic rings precontracted by EP (10 μM), and this effect was especially reduced in the presence of glibenclamide or nifedipine. However, PAAE (0.25-1 mg/mL) had only a minimal vasorelaxant effect on thoracic aortic rings precontracted by KCl (80 mM). The results demonstrate that the P. armeniaca aqueous extract possesses potent antihypertensive and vasorelaxant activity, and its vasorelaxant activity seems to be mediated through the opening of ATP-sensitive K+ channels and inhibition of L-type calcium channels.

Study of the Antihypertensive Effect of Laurus nobilis in Rats.

The study aimed to study the antihypertensive activity of Laurus nobilis. Laurus nobilis L. is used to treat hypertension in Morocco. The study was designed to investigate the effect of the aqueous extract leaves of Laurus nobilis (AELN) on blood pressure. The antihypertensive and vasorelaxant activities of AELN were pharmacologically investigated in normotensive and L-NAME-induced hypertensive rats. Thereafter, blood pressure was evaluated, and the ex-vivo vasorelaxant activity of this extract was performed. A considerable decrease in blood pressure parameters were observed in L-NAMEinduced hypertensive rats treated with AELN. The extract induced a vasorelaxant effect on the aorta precontracted with epinephrine or KCl by inhibiting extracellular Ca2+ entry. The study demonstrates that Laurus nobilis aqueous extract exhibits potent antihypertensive and vasorelaxant activities via inhibiting Ca2+ entry.

The Genus Cryptocarya: A Review on Phytochemistry and Pharmacological Activities.

Cryptocarya (the laurel family) is a large genus of great economic plants found in tropics and subtropics. Plants of this genus are a rich resource of essential oils, and pharmacological compounds. An overview of phytochemistry and pharmacological aspect is not yet available. This review aims to establish insightful information on phytochemistry, and pharmacological values. The literature collection is based on keywords 'Cryptocarya', 'phytochemistry', and 'pharmacology' using a broad panel of scientific sources, such as Google Scholar, Sciencedirect, and Wiley. Since the 1950s, Cryptocarya plants have been the main object in various phytochemical studies, by which about 390 metabolite compounds were isolated. Alkaloids, α-pyrones, and flavonoids could be seen as the main classes of Cryptocarya isolates. Cryptocarya constituents displayed potential pharmacological values such as anti-inflammatory, antimicrobial, antioxidative, antiviral, vasorelaxant activities, especially cytotoxicity.

Structurally diverse monoterpene indole alkaloids with vasorelaxant activities from the branches of Alstonia scholaris

Seven undescribed monoterpene indole alkaloids alstoscholarinines A‒G, along with nineteen known alkaloids, were isolated from the branches of Alstonia scholaris (L.) R. Br. The isolated alkaloids were classified into ten framework types. The structures of the undescribed alkaloids were elucidated by extensive spectroscopic analysis, ECD calculation, and single-crystal X-ray diffraction analysis. Alstoscholarinine A is an unreported and unusual monoterpene indole alkaloid incorporating three nitrogen atoms, characterized by a compact 6/5/6/6/6/5 hexacyclic system bearing a piperidine ring and a unique oxazolidine ring. Alstoscholarinine B represents the first naturally C-17 nor-isositsirikine-type alkaloid. Plausible biosynthetic pathways of alstoscholarinines A and B were proposed. All isolates were evaluated for their vasorelaxant activities against phenylephrine-induced contraction of rat mesenteric arteries. Among them, seven alkaloids showed significant vasorelaxant activities with EC50 values less than 10 μM. Importantly, the akuammicine-type alkaloids in this study showed much better vasorelaxant activities than other framework type alkaloids, indicating that this type of alkaloid may be a valuable source for the discovery of vasodilators. A preliminary structure-activity relationship for vasorelaxant activities of the isolated akuammicine-type alkaloids is also discussed.

Vasorelaxant Effect of Moroccan Cannabis sativa Threshing Residues on Rat Mesenteric Arterial Bed is Endothelium and Muscarinic Receptors Dependent.

Ethanolic fraction of Moroccan Cannabis sativa threshing residues (EFCS) was evaluated for its vasorelaxant activity. The current work aims to identify the active metabolites in the ethanolic fraction of the EFCS and illustrate their mechanism of action. Free radical scavenging capacity of EFCS was assessed using DPPH method. The EFCS vasodilation activities in phenylephrine-precontracted isolated rat mesenteric arterial beds were investigated in presence of L-NAME (nitric oxide synthase inhibitor), indomethacin (cyclooxygenase inhibitor), potassium channel blockers (namely tetraetylamonium, barium chloride, and glibenclamide), and atropine. Nitric oxide vascular release was measured by electron paramagnetic resonance (EPR) using a spin trap in rat aortic rings. EFCS induced dose-dependent vasorelaxation on mesenteric vascular bed. Incubation of the preparations with L-NAME, ODQ (a soluble guanylyl cyclase inhibitor), or potassium channel blockers reduced the fall of perfusion pressure caused by EFCS. Endothelial denudation or atropine abolished the EFCS's vasorelaxant effect, suggesting involvement of muscarinic receptors and endothelium-relaxing factors. The extract induced nitric oxide release in aortic rings in a similar manner as acetylcholine suggesting an effect of EFCS on the muscarinic receptor and the conductance arteries. Chemical investigation of EFCS identified potential active components namely apigenin and derivatives of luteolin skeleton and also additional components such as neophytadiene, squalene, and β-sitosterol. In conclusion, the vasorelaxant effect of EFCS on rat mesenteric arterial bed, which is dependent of muscarinic receptor activation, nitric oxide, and EDHF, can account for potential therapeutic use against high blood pressure related cardiovascular diseases.

Alscholarines A and B, two rearranged monoterpene indole alkaloids from Alstonia scholaris.

Alscholarines A and B (1 and 2), two unprecedented rearranged monoterpene indole alkaloids, were isolated from Alstonia scholaris. Alscholarine A (1) features an imidazole ring fused with a rearranged vallesamine-type alkaloid possessing an unparalleled 6/5/6/6 tetracyclic skeleton through an unprecedented C7-C-19 connectivity. Alscholarine B (2), incorporating an unusual 7-oxa-1-azabicyclo[3.2.1]octane moiety, represents a unique rearranged vallesamine-type alkaloid with a 6/5/6/6/5 ring system via an unprecedented C-6-C-20 connectivity. Their structures were established by spectroscopic analysis, X-ray crystallography, and quantum-chemical calculations. Their plausible biosynthetic pathways were proposed. The vasorelaxant and anti-inflammatory activities of them were also evaluated. Compounds 1-3 showed moderate vasorelaxant activities.

PS-BPB03-2: VASORELAXANT-MEDIATED ANTIHYPERTENSIVE EFFECT OF THE SEED AQUEOUS EXTRACT OF AFRAMOMUM PRUINOSUM GAGNEP. (ZINGIBERACEAE)

Objective: Despite the existing therapies, arterial hypertension is still a prevalent and a worldwide major public health concern, prompting the search for new therapeutic alternatives. The present study investigated the antihypertensive and the related mechanisms of action of the seed aqueous extract of Aframomum pruinosum (AEAP), a plant used in Cameroon traditional medicine against cardiovascular ailments. Design and method: Male Wistar rats were rendered hypertensive by chronic oral administration of L-NAME (30 mg/kg/day) for three consecutive weeks, and hypertensive rats were selected and treated with L-NAME alone or in combination with AEAP at doses of 75 or 150 mg/kg/day for an additional 3 consecutive weeks. Captopril (25 mg/kg/day, p.o) was used as reference drug. Blood pressure and heart rate were monitored weekly. At the end of the experiment, the heart was harvested, weighed, and sections of cardiac tissue were stained with hematoxylin and eosin for histological analysis. Cumulative concentrations of the aqueous extract (3, 10, 30, 100, and 300 μg/mL) were tested on intact or endothelium-denuded aorta rings precontracted with norepinephrine (NE; 1 μM) or KCl (90 mM) in absence or presence of L-NAME (a nitric oxide synthase inhibitor, 100 μM), indomethacin (a prostaglandin synthesis inhibitor; 10 μM), methylene blue (a guanylate cyclase inhibitor, 1 μM), tetraethylammonium (TEA; a non-specific potassium channel blocker; 5 μM) or glibenclamide (an ATP-sensitive potassium channel blocker; 10 μM). The contractile response to NE, or CaCl2 was also assessed in the presence or absence of the plant extract. Results: AEAP completely reversed (p < 0.001) L-NAME-induced elevated systolic and diastolic blood pressure, and increased heart rate. AEAP partially reversed cardiac hypertrophy, leucocyte infiltration, and prevent cardiac necrosis. AEAP induced a concentration-dependent vasorelaxant effect on NE- and KCl-evoked contraction with EC50 values of 13.46 and 49.37 μg/mL, respectively. Removal of the endothelium and the preincubation of aorta rings with L-NAME significantly (p < 0.05) reduced the vasorelaxant effect of the plant extract, while indomethacin and methylene blue had no effect (p > 0.05). Glibenclamide, similar to TEA, significantly (p < 0.001) inhibited the vasorelaxant response to AEAP. Also, the extract significantly (p < 0.01 and p < 0.001) inhibited NE- and CaCl2-induced contraction. Conclusion: AEAP possesses antihypertensive effects that are at least partially mediated by its vasorelaxant activity. Nitric oxide release, opening of KATP channels, blockade of alpha-1 receptors, and inhibition of Ca2+ influx account for this vasorelaxant activity.

Cardiovascular Activity of Ginkgo biloba-An Insight from Healthy Subjects.

Ginkgo biloba is the oldest living tree species in the world. Despite less than encouraging clinical results, extracts from its leaves are among the most used herbal preparations in the prevention and treatment of cardiovascular diseases. Most data on the efficacy of Ginkgo biloba on cardiovascular disease is from clinical studies, with few results from healthy subjects. This paper aims to provide a comprehensive review of the mechanisms underlying the known beneficial cardiovascular activities of Ginkgo biloba. It displays myocardial suppressant and vasorelaxant activities ex vivo, potentiating endothelial-dependent and -independent pathways. It improves perfusion in different vascular beds, namely ocular, cochlear, cutaneous, cerebral, and coronary. Although scarce, evidence suggests that Ginkgo biloba displays a heterogeneous effect on tissue perfusion which is dependent on the individual elimination pathways. It displays an acceptable safety profile, with most reported adverse reactions constituting rare occurrences. Collectively, Ginkgo biloba positively impacts cardiovascular physiology, improving hemodynamics and organ perfusion. In the future, better controlled clinical studies should be performed in order to identify the target populations who may benefit the most from pharmacotherapeutic interventions involving Ginkgo biloba.

Evaluation of vasodilatory effect and antihypertensive effect of chrysin through in vitro and sub-chronic in vivo study

Chrysin, a bioflavonoid belonging to the flavone, occurs naturally in plants such as the passionflower, honey and propolis. Few studies have demonstrated that chrysin can promote vasorelaxant activities in rats' aorta and mesenteric arteries. To date, no research has explored the signalling system routes that chrysin may utilise to produce its vasorelaxant action. Therefore, this study aimed to investigate the underlying mechanisms involved in chrysin-induced vasorelaxant in rats' aortic rings and assess the antihypertensive effect of chrysin in spontaneously hypertensive rats (SHRs). The findings revealed that chrysin utilised both endothelium-dependent and endothelium-independent mechanisms. The presence of L-NAME (endothelial NO synthase inhibitor), ODQ (sGC inhibitor), methylene blue (cGMP lowering agent), 4-AP (voltage-gated potassium channel inhibitor), atropine (muscarinic receptors inhibitor) and propranolol (β-adrenergic receptors inhibitor) significantly reduced the chrysin's vasorelaxant action. Furthermore, chrysin can reduce intracellular Ca2+ levels by limiting the extracellular intake of Ca2+ through voltage-operated calcium channels and blocking the intracellular release of Ca2+ from the sarcoplasmic reticulum via the IP3 receptor. These indicate that chrysin-induced vasorelaxants involved NO/sGC/cGMP signalling cascade, muscarinic and β-adrenergic receptors, also the potassium and calcium channels. Although chrysin had vasorelaxant effects in in vitro studies, the in vivo antihypertensive experiment discovered chrysin does not significantly reduce the blood pressure of SHRs following 21 days of oral treatment. This study proved that chrysin utilised multiple signalling pathways to produce its vasorelaxant effect in the thoracic aorta of rats; however, it had no antihypertensive effect on SHRs.

Effect of Calamintha officinalis on Vascular Contractility and Angiotensinconverting Enzyme-2.

The study aimed to assess the antihypertensive activity of Calamintha officinalis. Calamintha officinalis (CO) is a medicinal and aromatic herb as well as an antihypertensive plant that is widely used for its medicinal properties in several regions. This study aimed to evaluate the effect of the aqueous extract of Calamintha officinalis (AECO) on vasorelaxant activity and arterial blood pressure under normal and hypertensive states in rats. Additionally, the effect of AECO on vascular angiotensin-converting enzyme 2 (ACE-2) was assessed. In the current study, AECO (100 mg/Kg) was prepared, and its antihypertensive ability was assessed in L-NG-Nitro arginine methyl ester (L-NAME)-induced hypertensive rats. Blood pressure and heart rate were recorded for 6 h for the acute experiment and during seven days for the subchronic treatment. The results indicated that AECO reduced the systolic, diastolic, and mean arterial blood pressure in hypertensive rats. In addition, the study showed that AECO exerts a vasorelaxant ability through the sGC-cGMP induction pathway, vascular cyclooxygenase pathway, and the opening of K+ channels. However, AECO had no inhibitory effect on aortic ACE-2. The study illustrates the beneficial action of AECO as an antihypertensive and vasorelaxant agent.

Chromatographic Techniques and Pharmacological Analysis as a Quality Control Strategy for Serjania triquetra a Traditional Medicinal Plant.

Serjania triquetra is a medicinal plant widely used in traditional medicine for the treatment of urinary tract diseases, renal affections, and its complications. The population can buy this plant in folk markets as a raw material mixed with several herbal remedies or as a health supplement. On the market, two commercial presentations were found for the vegetal material; one had a bulk appearance and the other was marketed wrapped in cellophane bags (HESt-2, HESt-3). Nevertheless, the plant has not been exhaustively investigated and quality control techniques have not been developed. This research aimed to realize a phytochemical study using an authentic, freshly collected sample as a reference for S. triquetra (HESt-1), using the compounds identified. A method for the determination of preliminary chromatographic fingerprinting was developed. Additionally, the vasorelaxant effect from three samples was evaluated with ex vivo rat models. Thus, three hydroalcoholic extracts (HESt-1, HESt-2, and HESt-3) were prepared by maceration. A total of nine compounds were fully identified from HESt-1 after the extract was subjected to open-column chromatography. Seven metabolites were detected by gas chromatography, while ursolic acid (UA) and allantoin were isolated and identified using UPLC-MS and NMR, respectively. Three extracts were analyzed for their chromatographic fingerprint by UPLC-MS. Biological activity was explored by ex vivo rat aorta ring model to evaluate vasorelaxant activity. All extracts showed a vasorelaxant effect in a concentration-dependent and endothelium-dependent manner. S. triquetra vascular activity may be attributed to UA and allantoin compounds previously described in the literature for this activity.

Ursolic acid enhances the effect of exercise training on vascular aging by reducing oxidative stress in aged type 2 diabetic rats.

Ursolic acid (UA) mediates the vasorelaxant activity via nitric oxide (NO) release, and upregulation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) in disease conditions with increased oxidative stress (OS). The present study aimed to reflect on the impact of 8 weeks of a combination of UA supplementation and resistance/endurance training in old male Wistar rats having a high-fat diet and/or low-dose streptozotocin-induced type 2 diabetes (HFD/STZ-induced T2D), with an emphasis on Sirtuin 1 (SIRT1)-endothelial nitric oxide synthase (eNOS) axis and OS indices in their aortic tissues. A total number of56 21-month-old male Wistar rats with HFD/STZ-induced T2D were randomized into seven groups (n=eight animals per group): (1) sedentary old nondiabetic (Control [C]); (2) sedentary HFD/STZ-induced T2D (Diabetic [D]); (3) sedentary HFD/STZ-induced T2D plus UA (Diabetic + Ursolic Acid [DU]); (4) endurance-trained HFD/STZ-induced T2D (Diabetic + Endurance Training [DE]); (5) resistance-trained HFD/STZ-induced T2D (Diabetic + Resistance Training [DR]); (6) endurance-trained HFD/STZ-induced T2D plus UA (Diabetic + Endurance Training + Ursolic Acid [DEU]); and (7) resistance-trained STZ-diabetic plus UA (Diabetic + Resistance Training + Ursolic Acid [DRU]) rats. The ladder-based resistance training group performed the ladder resistance training at 60% of the maximum voluntary carrying capacity (MVCC), 14-20 climbs in each session, with a one-min rest between each two trials, 5 days a week. The treadmill-based endurance exercise training protocol consisted of repeated bouts of high- and low-intensity training with 60-75% maximal running speed and 30%-40% maximal running speed in the course of 8 weeks, respectively. The animals in the supplement groups also took 500 mg of UA/kg of high-fat diet/day, resulting in a daily UA intake of approximately 250 mg UA per kg of body weight rat/day. The resistance/endurance training plus the UA consumption could partially reverse the levels of malondialdehyde (MDA), nitric oxide (NO), as well as total antioxidant capacity (TAC). It was concluded that oral 0.5% UA supplementation can prevent vascular aging biomarkers in a HFD/STZ-induced T2D model. Further studies are also required to clarify how chronic consumption of UA with/without training protocols reverses vascular aging process.

Synthesis and Vasorelaxant Activity of Nitrate-Coumarin Derivatives.

Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate-coumarins and evaluated their vasorelaxant activity in contraction-relaxation studies using rat aorta rings precontracted with phenylephrine or by depolarization with a high concentration of potassium chloride. Four of the new compounds were able to relax smooth vascular muscle with a similar profile and potency to glyceryl trinitrate (IC50 =12.73 nM) and sodium nitroprusside (IC50 =4.32 nM). Coumarin-7-yl-methyl nitrate (4), the best compound within the series, was able to relax smooth vascular muscle in the low nanomolar range (IC50 =1.92 nM). The mechanisms of action have been explored, being the activation of sGC and the opening of K+ channels involved. Our studies indicate that the new nitrate derivatives are reversible and not deleterious for aortic rings, suggesting that these compounds have a potential interest for the development of new and highly efficient vasodilator drugs.