Synthesis and characterization of new pyrazole-tetrazole derivatives as new vasorelaxant agents.

The synthesis of new functionalized tetrazole-pyrazole compounds is reported. They were fully characterized by spectroscopy and spectrometry methods. The vasorelaxant potency of these molecules was also investigated. All compounds showed a good vasorelaxant activity but the Compound 6 "ethyl 1-((2-(3-bromopropyl)-2H-tetrazol-5-yl)methyl)-5-methyl-1H-pyrazole-3-carboxylate" seems to have the highest effect, which reached 70% at 10-4  M concentration. This effect was partially endothelium-dependent; also, the vasorelaxant pattern of this compound was quite similar to that of the verapamil.

Chenopodium ambrosioides induces an endothelium-dependent relaxation of rat isolated aorta.

OBJECTIVE: This study aims to evaluate the vasodilatory effect of Chenopodium ambrosioides on the isolated rat aorta, and to explore its mechanism of action. METHODS: The vasorelaxant effect and the mode of action of various extracts from the leaves of C. ambrosioides were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, ethyl acetate and methanol fractions were analyzed, using thin-layer chromatography and high-performance liquid chromatography techniques, for their polyphenolic content. RESULTS: The various active extracts of C. ambrosioides at four concentrations (10-3, 10-2, 10-1 and 1 mg/mL) relaxed the contraction elicited by phenylephrine, in a concentration-dependent manner. This effect seems to be endothelium-dependent, since the vasodilatory effect was entirely absent in denuded aortic rings. The vasorelaxant effect of the methanol fraction (MF) of C. ambrosioides at 1 mg/mL was also inhibited by atropine and tetraethylammonium. This effect remained unchanged by Nω-nitro-l-arginine methyl ester hydrochloride and glibenclamide. The preliminary phytochemical analysis showed that the leaves of C. ambrosioides are rich in phenolic and flavonoid derivatives. CONCLUSION: These results suggest that the MF of C. ambrosioides produces an endothelium-dependent relaxation of the isolated rat aorta, which is thought to be mediated mainly through stimulation of the muscarinic receptors, and probably involving the opening of Ca2+-activated potassium channels.

Artemisia campestris L.: review on taxonomical aspects, cytogeography, biological activities and bioactive compounds.

Artemisia campestris L. (Asteraceae) is a polymorphic species that consists of many subspecies and varieties. It is known for its medicinal, pharmacological, and culinary properties. This review is undertaken with the aim to highlight some aspects of this plant, specifically the taxonomy, the cytogeography, the phytochemistry with an emphasis on the structure-activity relationship (SAR) of the main bioactive compounds of A. campestris L. in addition to its biological properties and the food control properties. The bibliographic data compiled in this review allowed the revision of 146 papers, by using different databases and scientific engines, such as Scopus, ScienceDirect, Pubmed, and google scholar. The taxonomic analysis has embedded A. campestris L. in the tribe Anthemideae, and the genus Artemisia L. Also many subtaxa have been identified, and a subspecific classification of this species has been established on the basis of its botanical characters. The cytogenetic findings evidenced that A.campestris L. is prevailed by the chromosome number x = 9, with a polyploidization degree ranging from diploidy to hexaploidy according to the geographical distribution of the plant populations, while the genome size seems to be proportional to the ploidy level, suggesting an adaptive trait of the cytotypes to new environments. This plant is rich in polyphenols, flavonoids, and terpenic compounds, which substantiate the bioactivities attributed to its extracts and essential oil. Hence, the SAR of the main bioactive compounds of A. campestris L., mainly the prominent flavonoids, phenolic acids, and terpenes revealed a tight link between specific chemical entities of the bioactive compound and the respective biological activity. Many biological activities were approached in this review, mainly the antioxidant, antivenom, antidiabetic, antihyperlipidemic, anti-inflammatory, antihypertensive, anti-leishmaniasis, antinociceptive, wound healing, and analgesic activities in addition to the hepatoprotective, nephroprotective, neuroprotective, and gastroprotective actions. Finally, the food preservative ability of the extracts and essential oil obtained from A.campestris L. have been fully discussed. The present review contributes to the literature, by bringing more clarifications about the different aspects of A.campestris L., like taxonomy, cytogeography and biological interests of this species. The SAR approach of some constituents that occur in A.campestris L., gives a solid support that can be used to explore the bioactivity of components isolated from this species, while the preservative properties of this plant can be usefully exploited for the agrifood sector.

Antihypertensive and vasorelaxant effects of aqueous extract of Artemisia campestris L. from Eastern Morocco.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia campestris L. (Asteraceae) has many traditional uses, among which treatment of diabetes and hypertension. AIM OF THE STUDY: This study was conducted in order to confirm the antihypertensive and hypotensive effects of A. campestris L. aqueous extract (AcAE) and to explore the underlying mechanism of action of its vasorelaxant effect, besides the acute toxicity. Also, the chemical composition of AcAE was investigated. MATERIAL AND METHODS: the chemical content of AcAE was determined by using HPLC and NMR techniques. The antihypertensive effect was assessed indirectly by tail-cuff method on L-NAME induced hypertensive rats, while the hypotensive action was monitored intravenously by invasive method on normotensive rats. The vasorelaxant effect and vascular mechanism of action were studied in the presence of antagonists and blockers on aorta isolated from normotensive rats. On the other side, the acute toxicity was studied by oral feeding of extract to the mice. RESULTS: The global phytochemical profile of AcAE reveals the presence of several polyphenols as main components. A. campestris L. infusion was characterized by mono- and di-cinnamoyl compounds, with 3,5-dicaffeoylquinic (isochlorogenic A) acid being the main compound, followed by 5-caffeoylquinic (chlorogenic) acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant compound among flavonoids. The daily treatment with AcAE at 150mg/kg/day prevented the installation of hypertension on L-NAME hypertensive rats, and reduced SBP from 172mmHg up to 144mmHg. At the dose 40mg/kg, AcAE provoked reduction of systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP), without affecting the heart rate. Also, AcAE (10-2-2mg/ml) relaxed the precontracted aorta by 95.8±1.3%. The denudation and preincubation of aorta with atropine, calmidazolium, L-NAME, hydroxycobalamin, ODQ, 8-RP-Br-PET-cGMP, thapsigargin and verapamil attenuated the vasorelaxant response, while the pre-treatment with 4-AP, TEA, glibenclamide and BaCl2 did not alter this effect. The oral administration of AcAE (0-6g/kg) reveals no mortality or toxicity. CONCLUSIONS: our study proved that AcAE possess an important antihypertensive, hypotensive and vasorelaxant effect, which is mediated via calmodulin-NO-cGC-PKG pathway, and via inhibition of calcium influx through voltage-operated calcium channels and activation of intracellular calcium mobilization into sarcoplasmic reticulum. Therefore, our findings give first evidence about the traditional use of A. campestris L. as antihypertensive plant.

Chemical composition, vasorelaxant, antioxidant and antiplatelet effects of essential oil of Artemisia campestris L. from Oriental Morocco.

BACKGROUND: Artemisia campestris L. (Asteraceae) is a medicinal herb traditionally used to treat hypertension and many other diseases. Hence, this study is aimed to analyze the essential oil of A. campestris L (AcEO) and to investigate the antiplatelet, antioxidant effects and the mechanisms of its vasorelaxant effect. METHODS: The chemical composition of AcEO was elucidated using GC/MS analysis. Then, the antioxidant effect was tested on DPPH radical scavenging and on the prevention of ß-carotene bleaching. The antiplatelet effect was performed on the presence of the platelet agonists: thrombin and ADP. The mechanism of action of the vasorelaxant effect was studied by using the cellular blockers specified to explore the involvement of NO/GC pathway and in the presence of calcium channels blockers and potassium channels blockers. RESULTS: AcEO is predominated by the volatiles: spathulenol, ß-eudesmol and p-cymene. The maximal antioxidant effect was obtained with the dose 2 mg/ml of AcEO. The dose 1 mg/ml of AcEO showed a maximum antiplatelet effect of, respectively 49.73% ±9.54 and 48.20% ±8.49 on thrombin and ADP. The vasorelaxation seems not to be mediated via NOS/GC pathway neither via the potassium channels. However, pretreatment with calcium channels blockers attenuated this effect, suggesting that the vasorelaxation is mediated via inhibition of L-type Ca2+ channels and the activation of SERCA pumps of reticulum plasma. CONCLUSION: This study confirms the antioxidant, antiplatelet and vasorelaxant effects of A.campestris L essential oil. However, the antihypertensive use of this oil should be further confirmed by the chemical fractionation and subsequent bio-guided assays.