Hypoglycemic and Hypotensive Effects of Calycotome villosa Subsp. intermedia Seeds in Meriones shawi Rats: In Vivo, Ex Vivo, and In Vitro Investigations.

Calycotome villosa subsp. intermedia is used in traditional medicine for the prevention and self-treatment of a variety of illnesses, including diabetes mellitus, obesity, and hypertension. The present study aims to investigate the in vivo, ex vivo, and in vitro hypoglycemic and hypotensive effects of the lyophilized aqueous extract of Calycotome villosa subsp. intermedia seeds (CV) on Meriones shawi submitted to hypercaloric diet and physical inactivity (HCD/PI) for 12 weeks. This diet induces a type 2 diabetes/metabolic syndrome phenotype with hypertension. Furthermore, HCD/PI decreased aorta contraction due to noradrenaline, enhanced L-arginine, and depressed insulin-evoked relaxation, while the relaxing effects of the NO donor SNAP and of diazoxide were unchanged. In vivo experiments showed that the oral administration of the CV extract (50 mg/kg b.wt) for 3 consecutive weeks significantly attenuated the development of type 2 diabetes, obesity, dyslipidemia, and hypertension. These effects may involve the improvement of lipid metabolism, insulin sensitivity, systolic arterial pressure, and urine output. Additionally, ex vivo and in vitro investigations revealed that CV treatment improved vascular contraction to noradrenaline, induced a slight aorta relaxation in response to carbachol, increased the vasorelaxation effect evoked by insulin, and depressed the L-arginine evoked relaxation. However, CV did not change the endothelium-independent vasorelaxation response evoked by SNAP or diazoxide. Hence, the present study provides useful information and supports the traditional use of CV in the prevention and self-treatment of numerous ailments. Overall, it can be concluded that Calycotome villosa subsp. intermedia seed extracts might be useful in the management of type 2 diabetes and hypertension.

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.

Evaluation of cytotoxic effects and acute and chronic toxicity of aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) in rodents.

OBJECTIVE: The present investigation was carried out to evaluate the safety of an aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) by determining its cytotoxicity and potential toxicity after acute and sub-chronic administration in rodents. MATERIALS AND METHODS: Cytotoxic activity was tested in cancer and non-cancer cell lines HeLa, Mel-5, HL-60 and 3T3. Acute toxicity tests were carried out in mice by a single oral administration of Calycotome seed-extract (0 - 12 g/kg) as well as intraperitoneal doses of 0 - 5 g/kg. Sub-chronic studies were conducted in Wistar rats by administration of oral daily doses for up to 90 days. Changes in body and vital organ weights, mortality, haematology, clinical biochemistry and histologic morphology were evaluated. RESULTS: The lyophilized aqueous extract of C. villosa exhibited a low cytotoxicity in all cell lines tested with an IC50 > 100 µg/ml. In the acute study in mice, intra-peritoneal administration caused dose-dependent adverse effects and mortality with an LD50 of 4.06 ± 0.01 g/kg. In the chronic tests, neither mortality nor visible signs of lethality was seen in rats. Even AST and ALT were not affected while a significant decrease in serum glucose levels, at 300 and 600 mg/kg was detected. Histopathological examination of the kidney and liver did not show any alteration or inflammation at the end of treatment. CONCLUSION: In conclusion, the aqueous extract of C. villosa seed appeared to be non-toxic and did not produce mortality or clinically significant changes in the haematological and biochemical parameters in rats.

Characterization of vascular dysregulation in meriones shawi after high-calorie diet feeding.

The present study was initiated to characterize vascular dysregulations (contraction and relaxation) associated with metabolic defects in Merions shawi, a rodent from the gerbillidae family, submitted to 12 weeks high-calorie diet. This diet induces a type 2 diabetes/metabolic syndrome phenotype with hypertension. In diabetic meriones, body weight increase was associated with hyperglycemia, increased insulinemia, and insulin resistance. Compared to lean meriones, diabetic meriones showed decreased aorta contraction to noradrenaline, which was normalized after NOS inhibition. Endothelium-dependent relaxation to carbachol was enhanced, while relaxing effects of the NO donor SNAP and of diazoxide were unchanged. Insulin-evoked relaxation was depressed in aorta from diabetic meriones, and L-arginine relaxed contracted arteries from diabetic meriones, but not from lean meriones. Urine NOX level and iNOS mRNA muscle expression were significantly higher in diabetic meriones compared to lean animals. These data strongly suggest that iNOS may have a pathogenic role in vascular dysfunction observed in diet-induced diabetic meriones.

Vasorelaxant effect of essential oil isolated from Nigella sativa L. seeds in rat aorta: Proposed mechanism.

The effect of the essential oil extracted from Nigella sativa (L.) seeds (Nigella oil) was investigated for its vasorelaxant activity on isolated rat aorta. Nigella oil at concentrations of 10-100 µg/mL elicited a dose-dependent relaxation of the aorta, which was pre-contracted with noradrenaline (NA, 10(-6) M) or KCl (100mM). In the presence of Nigella oil (75 µg/mL, the dose response curves to increasing concentrations of NA (10(-9) M to 10(-4)M) or KCl (10mM-100mM) were displaced downwards, indicating inhibition of the vasoconstrictive effect. This relaxation effect was independent of the presence of endothelium. In addition, the vasodilatory activity of the Nigella oil was not affected by pre-treatment of the rings with N(G)-nitro-L-Arginine (an inhibitor of endothelial nitric oxide synthase; 0.1mM), suggesting that the vasorelaxant effect is not mediated by nitric oxide. Furthermore, pre-treatment of the rings with Nigella oil (75 µg/mL suppressed the tension increment produced by increasing external calcium concentration (0.25 mM to 1.5mM). Tin conclusion, the essential oil extracted from Nigella sativa seeds produces smooth muscle relaxation, which is independent of endothelium and is not mediated by nitric oxide. The results also suggest that the vasorelaxing effect of the oil results from the blockade of both voltage-sensitive and receptor-operated calcium channels, and this may have therapeutic significance, in that Nigella oil may be useful as an antihypertensive agent in humans.