An Investigation of Novel Series of 2-Thioxo-1,3-dithiol-carboxamides as Potential Antispasmodic Agents: Design, Synthesis via Coupling Reactions, Density Functional Theory Calculations, and Molecular Docking.

This study reports the synthesis of 2-thioxo-1,3-dithiol-carboxamides (TDTCAs) under mild conditions at room temperature using HBTU as a coupling agent, which significantly improved amide bond formation. The synthesized compounds were characterized using several analytical techniques, including 1H and 13C NMR spectroscopy, and HRMS, confirming their intended structures and structural integrity. A DFT computational study at the B3LYP/6-31G(d,p) level was conducted on the four synthesized compounds to compare their electronic properties and molecular structures. The results showed that these compounds demonstrated antispasmodic effects on jejunum contractions. Molecular docking revealed that compounds c and d displayed the highest docking scores on potassium and voltage-gated calcium channels and adrenergic receptors. In summary, compounds c and d exhibit antispasmodic effects, potentially blocking alpha-adrenergic receptors and calcium channels, thus providing a scientific basis for their potential use in treating gastrointestinal disorders.

Vasorelaxant Mechanism of Herbal Extracts from Mentha suaveolens, Conyza canadensis, Teucrium polium and Salvia verbenaca in the Aorta of Wistar Rats.

Mentha suaveolens (MS), Conyza canadensis (CC), Teucrium polium (TP) and Salvia verbenaca (SV) are used in Morocco to treat hypertension. Our aim was to characterize the composition and vasoreactivity of extracts of MS, CC, TP and SV. The chemical compositions of aqueous extracts of MS, SV and TP, and of a hydromethanolic extract of CC, were identified by HPLC-DAD. The vasoreactive effect was tested in rings of the thoracic aorta of female Wistar rats (8-14 weeks-old) pre-contracted with 10 µM noradrenaline, in the absence or presence of L-NAME 100 µM, indomethacin 10 µM or atropine 6 µM, to inhibit nitric oxide synthase, cyclooxygenase or muscarinic receptors, respectively. L-NAME and atropine decreased the vasorelaxant effect caused by low concentrations of MS. Atropine and indomethacin decreased the vasorelaxant effect of low concentrations of SV. High concentrations of MS or SV and the effect of SV and TP were not altered by any antagonist. The activation of muscarinic receptors and NO or the cyclooxygenase pathway underlie the vasorelaxant effect of MS and SV, respectively. Neither of those mechanisms underlines the vasorelaxant effect of CC and TP. These vasorelaxant effect might support the use of herbal teas from these plants as anti-hypertensives in folk medicine.

Centaurium Erythraea Extracts Exert Vascular Effects through Endothelium- and Fibroblast-dependent Pathways.

Centaurium erythraea is a plant used in traditional medicine for several cardiovascular disorders, namely hypertension, but there is no scientific evidence able to provide a molecular basis for its claimed antihypertensive effects. After a preliminary screen of extracts obtained from sequential extraction of C. erythraea aerial parts, effects of the methanolic fraction (MFCE) on changes in perfusion pressure of isolated rat mesenteric vascular bed (MVB) and in rat cardiac fibroblasts proliferation were investigated, gathering information on the mechanisms involved in endothelium-dependent effects and their dependence on a pro-proliferative stimulus. The HPLC-DAD determination of the phenolics content of MFCE revealed the presence of 22 phenolic compounds. MFCE reduced (63.3 ± 3.9%; n = 4) perfusion pressure in MVB and almost completely abrogated the Ang II-induced increase in cardiac fibroblasts proliferation. Reduction of the perfusion pressure caused by MFCE was endothelium-dependent and occurred in parallel with an increase in NO release. These effects were inhibited by muscarinic receptor antagonists, by L-NAME (a NO synthase inhibitor), and by ODQ (a soluble guanylate cyclase inhibitor). Experiments revealed that effects required the involvement of K+ channels, being inhibited by tetraethylamonium (TEA; a Ca2+ activated K+ channels inhibitor) and by glibenclamide (an ATP-sensitive K+ channels inhibitor). In conclusion, extracts from C. erythraea, particularly the compounds present in the MFCE, induce endothelium-dependent vasodilation and prevent fibroblast proliferation induced by angiotensin II, which can account for the claimed antihypertensive effects of C. erythraea in traditional medicine.

Prevalence of and risk factors for overweight and obesity among adolescents in Morocco.

BACKGROUND: Overweight and obesity among children and adolescents is a major public health concern and their prevalence is increasing worldwide at an alarming rate in both developing and developed countries. AIMS: The objective of this study was to assess the prevalence of overweight and obesity in a representative sample of 12-18-year-old schooled adolescents in Fez, Morocco, and to investigate the possible risk factors associated with adolescent obesity. METHODS: A cross-sectional study was conducted between September 2014 and March 2015 in public secondary schools. Data were collected from a questionnaire. Weight and height were measured, and body mass index was calculated. Weight was classified according to the reference curves of WHO (2007). Data on 1818 adolescents aged 12-18 years were used. RESULTS: The prevalence of overweight was 7.69% and that of obesity was 3.41%. Overweight and obesity in adolescents were positively correlated to having a father (odds ratio (OR) = 1.58, P = 0.008) or a mother with higher education (OR = 1.56, P = 0.009). High family income (OR = 2.115, P = 0.028), motorized transport to school (adjusted OR = 1.77, P = 0.017), using a computer for > 4 h/day (OR: 2.56, P = 0.004) and frequent consumption of soda and soft drinks (OR = 1.42, P = 0.04) were also correlated with an increased risk for overweight and obesity. CONCLUSIONS: This study provides useful findings that could be elaborated on and expanded in studies on overweight and obesity among adolescents in Morocco.

Flavonoids as G Protein-coupled Receptors Ligands: New Potential Therapeutic Natural Drugs.

G protein coupled receptors (GPCRs) are among the largest family of cell surface receptors found in the human genome. They govern a wide range of physiological responses in both health and diseases, making them one of the potential targeted surface receptors for pharmaceuticals. Flavonoids can modulate GPCRs activity by acting as allosteric ligands. They can either enhance or reduce the GPCR's effect. Emerging research shows that individual flavonoids or mixtures of flavonoids from plant extracts can have relevant pharmacological effects against a number of diseases, particularly by influencing GPCRs. In the present review, we are considering to give a comprehensive overview of flavonoids and related compounds that exhibit GPCRs activity and to further explore which beneficial structural features. Molecular docking was used to strengthen experimental evidence and describe flavonoid-GPCRs interactions at molecular level.

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

Introduction: 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. Methods: 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. Results: 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 ß-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.

Anxiolytic and Antidepressant-Like Effects of Conyza canadensis Aqueous Extract in the Scopolamine Rat Model.

Conyza canadensis is a plant widely used in traditional medicine in Morocco for the treatment of varied health challenges. However, to the best of our knowledge, there is no scientific study justifying the traditional use of Conyza extract as an anxiolytic and antidepressant agent. Moreover, data regarding the polyphenolic fraction is limited. Therefore, the present study was conducted to investigate the chemical composition of an aqueous extract obtained from the aerial parts of Conyza, its antioxidant potential, and the anxiolytic and antidepressant-like effects of the sample (100 and 200 mg/kg body weight (bw)) in the scopolamine (Sco) (0.7 mg/kg bw) rat model. To achieve this purpose, a variety of antioxidant tests (including free radical-scavenging activity and lipoxygenase-inhibitory potential assays) and behavioral procedures, such as the elevated plus-maze and forced swimming tests, were performed. The results demonstrated that the aqueous extract of Conyza canadensis is rich in catechins and flavonoids which possess good antioxidant activity. Additionally, concentrations of 100 and 200 mg/kg of the extract exhibited significant anxiolytic and antidepressant-like profiles following scopolamine treatment. Therefore, we propose that the use of Conyza canadensis could be a new pharmacological target for the amelioration of major depression.

Acute and sub-chronic toxicity studies of the aqueous extract from leaves of Cistus ladaniferus L. in mice and rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistus ladaniferus L. (C.ladaniferus) (Cistaceae) is an aromatic shrub native to the Mediterranean region. The leaves are widely used in traditional medicine throughout Morocco for the treatment of various diseases including, diabetes, diarrhea, inflammation, and skin ailments. However, to the best of our knowledge, no systematic study concerning its toxicity profile has been reported. AIM OF THE STUDY: The study carried out evaluates the potential toxicity of the aqueous extract from leaves of the C.ladaniferus (CL extract) shrub, through the method of acute and sub-chronic oral administration in mice and rats. MATERIALS AND METHODS: During the acute toxicity study, male and female mice were orally administrated with CL aqueous extract at single doses of 500, 1000, 2000, 3000 and 5000mg/kg (n = 5/group/sex). Abnormal behavior, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. During the sub-chronic toxicity study, the aqueous extract was administered orally at doses of 500, 700 and 1000mg/kg (n = 6/group) daily to Wistar rats of both sexes for 90 days. The general behavior of the rats was observed daily, and their body weight was recorded weekly. A urinalysis, biochemical analysis, hematological analysis, macroscopic examination and histopathological examination of several organs were conducted at the end of the treatment period. RESULTS: During the acute toxicity test, when mice were administered doses of 3000 and 5000mg/kg, the CL extract produced a 10-30% mortality rate, respectively, and induced signs of toxicity. However, no mortality or adverse effect was noted at the doses of 1000 and 2000mg/kg. The median lethal dose (LD50) of the extract was estimated to be more than 5000mg/kg. In the subchronic study, the CL extract induced no mortality or treatment-related adverse effects with regard to body weight, general behavior, relative organ weights, urine, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal architecture suggesting no morphological alterations. Moreover, the CL extracts improved lipid profile and exhibited a significant hypoglycemic effect in all doses tested in rats. CONCLUSION: The results of the present study suggest that treatment with the CL extract for 13 weeks does not appear to produce significant toxicity, except at high dose. Therefore, the use of appropriate levels of the CL extract as a traditional medicine remedies should have a wide margin of safety for its therapeutic use.