Fatty acids characterisation by GC-MS, antiglycation effect at multiple stages and protection of erythrocytes cells from oxidative damage induced by glycation of albumin of Opuntia ficus-indica (L.) Mill seed oil cultivated in Eastern Morocco: Experimental and computational approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia ficus-indica (L.) Mill is frequently observed in the Moroccan traditional medicinal system, where these approaches are employed to mitigate the onset of diabetes and the subsequent complications it may entail. AIM OF THE STUDY: The aim of this research was to examine the effectiveness of Opuntia ficus-indica seed oil in preventing diabetic complications. Specifically, the study assessed its ability to counteract glycation at various stages, protected red blood cells from the harmful effects of glycated albumin, and inhibited pancreatic lipase digestive enzymes to understand its potential antihyperglycemic properties. Additionally, the study aimed to identify the chemical components responsible for these effects, evaluate antioxidant and anti-inflammatory properties, and conduct computational investigations such as molecular docking. MATERIALS AND METHODS: The assessement of Opuntia ficus-indica seed oil antiglycation properties involved co-incubating the extract oil with a bovine serum albumin-glucose glycation model. The study investigated various stages of glycation, incorporating fructosamine (inceptive stage), protein carbonyls (intermediate stage), and AGEs (late stage). Additionally, measurement of ß-amyloid aggregation of albumin was performed using Congo red, which is specific to amyloid structures. Additionally, the evaluation of oil's safeguarding effect on erythrocytes against toxicity induced by glycated albumin included the measurement of erythrocyte hemolysis, lipid peroxidation, reduced glutathione. The fatty acid of Opuntia ficus-indica seed oil were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The in vitro evaluation of antihyperglycemic activity involved the use of pancreatic lipase enzyme, while the assessement of antioxidant capability was carried out through the utilization of the ABTS and FRAP methods. The in vitro assessement of the denaturation of albumin activity was also conducted. In conjunction with the experimental outcomes, computational investigations were undertaken, specifically employing ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. Furthermore, molecular docking was utilized to predict antioxidant and antiglycation mechanisms based on protein targets. RESULTS: In vitro glycation assays, Opuntia ficus-indica seed oil displayed targeted inhibitory effects at multiple distinct stages. Within erythrocytes, in addition to mitigating hemolysis and lipid peroxidation induced by glycated albumin. GC-MS investigation revealed a richness of fatty acids and the most abundant compounds are Linoleic acid (36.59%), Palmitic acid (20.84%) and Oleic acid (19.33%) respectively. The findings of antioxidant ability showed a remarkable activity on FRAP and ABTS radicals. This oil showed a pronounced inhibitory impact (p < 0.001) on pancreatic lipase enzyme. It also exerted a notibale inhibition of albumin denaturation, in vitro. CONCLUSION: The identified results were supported by the abundant compounds of fatty acids unveiled through GC-MS analysis, along with the computational investigation and molecular docking.

The effect of Argania spinosa seed oil on diabetic nephropathy in streptozotocin-induced diabetes in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes is a significant metabolic disease impacting many of the world's population. In Morocco, a wide range of medicinal plants has taken great importance in the treatment of diabetes, among these plants; we find Argania spinosa (L.) Skeels. AIM: The objective of our work is based on the evaluation of the effect of roasted (Roil) and unroasted (UnRoil) Argan seed oil on diabetic nephropathy. MATERIALS AND METHODS: Roasted and unroasted oils from Argania spinosa (L.) Skeels seeds were examined for their effects on diabetic nephropathy using an experimental streptozotocin-induced model. Biochemical and histopathological analyses were conducted on blood and kidney samples to assess renal function and tissue damage. RESULTS: Both oils ameliorated significantly diabetic nephropathy symptoms. They limited the renal damage caused by streptozotocin and improved diabetes symptoms, including blood glucose levels, body weight, water intake, urinary volume, and kidney parameters. This activity could be elucidated by the antioxidant effect of Argan oil, enabling to neutralize free radicals and undertake a fundamental role in preventing the onset of these complications. CONCLUSION: Based on our findings, Argan oil could be used as dietary supplement for people with diabetes as a preventive measure against the emergence of diabetic complications.

Computational Evaluation of Bioactive Compounds from Dysphania ambrosioides Leaves.

Dysphania ambrosioides has been reported to have many medicinal properties, due to its possession of a multitude of biologically active molecules contained in its leaves. However, very few studies have been reported to evaluate their pharmacological properties. Consequently, in the present study, many computational tools have been performed to predict drug similarity and ADMET properties. Besides, the inhibitory potential of D.ambrosioides major compounds against Bacterial, Fungal and cardiovascular main receptor targets has been investigated. This study suggests that Carvone oxide, 5-Isopropenyl-2-Methylenecyclohexanol, and Caryophyllene oxide were the most active molecules belonging to D. ambrosioides Leaves, possessing drug-likeness with satisfactory bioactivity scores, having good pharmacokinetic values. Metabolism and toxicities were further studied using FAME3, GLORY, and pred-hERG. Slight cardiotoxicity and cytotoxicity were predicted, respectively, for Caryophyllene oxide and Carvone oxide, 5-Isopropenyl-2-Methylenecyclohexanol. Good inhibitory activities of the three compounds against Bacterial, Fungal, and Cardiovascular receptor targets. Hence, this is a comprehensive in silico approach to evaluate D.ambrosioides Leaves main phytocompounds in the background of its potential in future drug development.

Macromolecules: Synthesis, antimicrobial, POM analysis and computational approaches of some glucoside derivatives bearing acyl moieties.

Macromolecules i.e., carbohydrate derivatives are crucial to biochemical and medical research. Herein, we designed and synthesized eight methyl α-D-glucopyranoside (MGP) derivatives (2-8) in good yields following the regioselective direct acylation method. The structural configurations of the synthesized MGP derivatives were analyzed and verified using multiple physicochemical and spectroscopic techniques. Antimicrobial experiments revealed that almost all derivatives demonstrated noticeable antifungal and antibacterial efficacy. The synthesized derivatives showed minimum inhibitory concentration (MIC) values ranging from 0.75 µg/mL to 1.50 µg/mL and minimum bactericidal concentrations (MBCs) ranging from 8.00 µg/mL to 16.00 µg/mL. Compound 6 inhibited Ehrlich ascites carcinoma (EAC) cell proliferation by 10.36% with an IC50 of 2602.23 µg/mL in the MTT colorimetric assay. The obtained results were further rationalized by docking analysis of the synthesized derivatives against 4URO and 4XE3 receptors to explore the binding affinities and nonbonding interactions of MGP derivatives with target proteins. Compound 6 demonstrated the potential to bind with the target with the highest binding energy. In a stimulating environment, a molecular dynamics study showed that MGP derivatives have a stable conformation and binding pattern. The MGP derivatives were examined using POM (Petra/Osiris/Molinspiration) bioinformatics, and as a result, these derivatives showed good toxicity, bioavailability, and pharmacokinetics. Various antifungal/antiviral pharmacophore (Oδ-, O'δ-) sites were identified by using POM investigations, and compound 6 was further tested against other pathogenic fungi and viruses, such as Micron and Delta mutants of SARS-CoV-2.

Exploring Carob (Ceratonia siliqua L.): A Comprehensive Assessment of Its Characteristics, Ethnomedicinal Uses, Phytochemical Aspects, and Pharmacological Activities.

The carob tree (Ceratonia siliqua L.) is currently considered one of the most valuable fruit and forest trees in various fields and sectors of activity. It is a versatile plant, belonging to the Fabaceae family. It is widely used in traditional medicine to treat many diseases such as diabetes, hypertension, and gastrointestinal disorders, given that all its parts (leaves, flowers, pods, seeds, wood, bark, and roots) are useful and hold value in many areas. Its importance has increased significantly in recent years. Originating from the Middle East, it is recognized for its ecological and industrial significance. Previous studies conducted on Ceratonia siliqua L. have revealed the presence of several compounds, including polyphenols, flavonoids, carbohydrates, minerals, and proteins. The carob tree demonstrates antihypertensive, antidepressant, anti-obesity, and antihyperglycemic activities. This plant is known for its medicinal and therapeutic virtues. Moreover, it is particularly interesting to consider the pharmacological activities of the major phytochemical compounds present in the different extracts of this plant, such as phenolic acids, for example, coumaric and gallic acids, as well as flavonoids such as kaempferol and quercetin. Therefore, this review aims to analyze some aspects of this plant, especially the taxonomy, cytogeography, traditional uses, phytochemical constituents, and pharmacological activities of Ceratonia siliqua L., in addition to its biological properties.

Antihyperglycemic potential of the Lavandula stoechas aqueous extract via inhibition of digestive enzymes and reduction of intestinal glucose absorption.

BACKGROUND: Diabetes mellitus is a widespread metabolic disorder affecting global populations. Lavandula stoechas from Moroccan traditional medicine is used for its potential anti-diabetic effects. OBJECTIVE: This study aims to evaluate the antihyperglycemic impact of the aqueous extract of L. stoechas (AqLs) and explore its mechanisms. METHODS: The study employed a glucose tolerance test (OGTT) on normal and diabetic Wistar rats, administering AqLs at 150 mg/kg. In vitro, AqLs was tested against α-glucosidase and α-amylase activities, confirmed in vivo using normal and Allx-diabetic rats. The extract's impact on intestinal d-glucose absorption was assessed using the jejunum segment perfusion technique at 250 mg/kg in situ. Albino mice were used to assess toxicity. RESULTS: AqLs significantly reduced postprandial hyperglycemia (P < 0.001) due to glucose overload. It inhibited pancreatic α-amylase (IC50: 0.485 mg/mL) and intestinal α-glucosidase (IC50: 168 µg/mL) in vitro. Oral AqLs at 150 mg/kg reduced hyperglycemia induced by sucrose and starch in normal and diabetic rats. It also lowered (P < 0.001) intestinal glucose absorption in situ at 250 mg/kg. Oral acute toxicity tests on Albino mice indicated no adverse effects at different doses. CONCLUSION: to summarize, L. stoechas has evident antihyperglycemic effects attributed to inhibiting intestinal glucose absorption and key monosaccharide digestion enzymes like α-amylase and α-glucosidase.

Effects of Walnut Bark Extract on the Human Platelet Aggregation, Adhesion, and Plasmatic Coagulation In Vitro.

Thrombosis is the formation of a clot within a blood vessel. Antithrombotic drugs are used for treating thrombosis, which can be the cause of hemorrhage. Currently, there is a need to discover novel antithrombotic drugs. Walnut is widely used to treat a wide range of health complaints. In this study, walnut bark extract was tested in hemostasis parameters: platelets adhesion, aggregation, and plasmatic coagulation in human blood. The crude aqueous extract of walnut bark was prepared by infusion and tested in vitro on hemostasis. Through blood collection from healthy volunteer donors, we studied different parameters of the primary hemostasis: platelet adhesion on the collagen-coated surface under flow, ADP, collagen, thrombin, and arachidonic acid-induced platelet aggregation, and of the secondary hemostasis by measuring prothrombin time (PT) and activated partial thromboplastin (APTT) parameters. All experiments are realized in the absence and presence of the extract and repeated at least twice. The obtained data showed that the extract (1 and 2 mg/mL) significantly (p < 0.001) reduced the activated platelet adhesion on the collagen-coated surface. In the same way, the effect of the extract on platelet aggregation seems to depend on its concentration and on the nature of the agonist. The strongest inhibition of aggregation was observed in the case of collagen at 1 mg/mL, while there was no observed effect on arachidonic acid-induced aggregation. Moreover, the extract (1 mg/mL) affects the extrinsic, intrinsic, and common pathways of the human blood coagulation cascade by extending significantly (p < 0.001), both PT and APTT times. This study provides evidence that walnut bark extract, by its antiadhesive, antiaggregant, and anticoagulant activities, could be considered as a serious source of biological compounds for the prevention and treatment of thrombosis.

Protective Effect of Opuntia dillenii (Ker Gawl.) Haw. Seed Oil on Gentamicin-Induced Nephrotoxicity: A Biochemical and Histological Analysis.

Opuntia dillenii is a medicinal plant with frequent usage in folk medicine to treat many illnesses. The present study aims to investigate the protective effect of Opuntia dillenii seed oil against gentamicin-induced nephrotoxicity in rats. The animals (rats) were randomly divided into three groups (i) the normal control group treated only with distilled water (10 mL/kg), (ii) the gentamicin group treated with distilled water (10 mL/kg) and received an intraperitoneal injection of gentamicin (80 mg/kg), and (iii) the group treated with the Opuntia dillenii seed oil (2 mL/kg) and also received an intraperitoneal injection of gentamicin (80 mg/kg). The rats received their following treatments for 14 consecutive days orally. Serum urea, creatinine, gamma-glutamyl transferase, albumin, and electrolyte levels were quantified as the markers of acute renal and liver failure. Besides, the kidney and liver relative weight, kidney malondialdehydes, and kidney histological analysis were determined. The results have shown that daily pretreatment with Opuntia dillenii seed oil (2 mL/kg) prevented severe alterations of biochemical parameters and disruptions of kidney tissue structures. In addition, the results of the present study showed for the first time that Opuntia dillenii seed oil reduced renal toxicity in gentamicin-induced nephrotoxicity in rats. Therefore, Opuntia dillenii seed oil may represent a new therapeutic avenue to preserve and protect renal function in gentamicin-treated patients.

Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action.

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO's effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC50 = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC50 = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.

Acute and Subacute Toxicity and Cytotoxicity of Opuntia Dillenii (Ker-Gawl) Haw. Seed Oil and Its Impact on the Isolated Rat Diaphragm Glucose Absorption.

This study aims to assess the safety of the Opuntia dillenii (Ker-Gawl) haw. seed oil (ODSO) and its effect on the glucose absorption activity of the isolated rat hemidiaphragm. This oil's safety was studied by exploring its acute (doses 1, 3, 5, and 7 mL/kg) and subacute (doses 1 and 2 mL/kg) toxicities in albino mice and Wistar rats, respectively. The safety of the ODSO was also assessed by studying its effect on the HepG2 cell viability in vitro. The effect of ODSO, or combined with the insulin, on the glucose absorption activity of isolated rat hemidiaphragm was evaluated at the dose 1 g/L in vitro. The results demonstrated the safety of ODSO. Indeed, this study showed that this oil does not produce any mortality or signs of toxicity after the single-dose administration in mice. Additionally, the daily intake of the ODSO during four weeks does not induce a significant variation in the biochemical parameters and body weight of rats compared with the control group. Besides, the cell viability of HepG2 did not change in the presence of ODSO. On the other hand, the ODSO increased the glucose absorption activity of the isolated rat hemidiaphragm, and this activity was significantly enhanced when combined with insulin. This study confirms, on one side, the safety of this oil and its efficacy and, on the other side, encourages its potential use as a complement to treat diabetes.

Diabetic retinopathy in the Eastern Morocco: Different stage frequencies and associated risk factors.

Diabetes is a major cause of morbidity and mortality worldwide. It can affect many organs and, over time, leads to serious complications. Diabetic retinopathy (DR), a specific ocular complication of diabetes, remains the leading cause of vision loss and vision impairment in adults. This work is the first in Eastern Morocco aimed at identifying the different stages of DR and to determine their frequencies and associated risk factors. It is a case-control study conducted from December 2018 to July 2019 at the ophthalmology department of Al-Irfane Clinic (Oujda). Data were obtained from a specific questionnaire involving 244 diabetic patients (122 cases with retinopathy vs 122 controls without retinopathy). All results were analyzed by the EPI-Info software. This study shows a predominance of proliferative diabetic retinopathy (PDR) with 57.4% of cases (uncomplicated proliferative diabetic retinopathy (UPDR): 23.8%; complicated proliferative diabetic retinopathy (CPDR): 33.6%). The non-proliferative diabetic retinopathy (NPDR) represents 42.6% (minimal NPDR: 8.2%; moderate NPDR: 26.2%; severe NPDR: 8.2%). The determinants of DR were insulin therapy, high blood pressure, poor glycemic control and duration of diabetes. Regarding the chronological evolution, retinopathy precedes nephropathy. Diabetic nephropathy (DN) was present in 10.6% of cases especially in patients with PDR. In summary, the frequency of PDR was higher than that of NPDR. DR appears before DN with a high frequency of DN in patients with PDR. Good glycemic control and blood pressure control, as well as early diagnosis are the major preventive measures against DR.

Evaluation of Hepatoprotective Activity of Caralluma europaea Stem Extract against CCl4-Induced Hepatic Damage in Wistar Rats.

The present study aims to evaluate the hepatoprotective activity of stem aqueous extract of Caralluma europaea (AECe) on carbon tetrachloride- (CCl4-) induced hepatic damage in Wistar rats. The animals were daily treated with the aqueous extract of C. europaea at a dose of 250 mg/kg body weight for 14 days. CCl4 was injected (1 ml/kg, i.p.) two times, on the 7th and 14th days. At the end of the experimental period, all rats were anesthetized to collect blood for the assessment of biochemical parameters and then sacrificed to collect the liver for weighing. Hepatotoxicity was evaluated by measuring the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (total and direct), malondialdehyde (MDA), total protein (TP), triglycerides (TG), total cholesterol, very low-density lipoprotein (VLDL-c ), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), urea, creatinine, and uric acid. Based on the results obtained in this study, the administration of C. europaea before exposure to the administration of CCl4 conferred favorable hepatoprotective effect in rats. The treatment with AECe (250 mg/kg) exhibits a significant hepatoprotective effect by ameliorating CCl4-induced alterations of these biochemical parameters. Hence, C. europaea could be a potential medicinal herb that can be used in the future to prevent liver intoxication.

Phenolic Content and Antioxidant, Antihyperlipidemic, and Antidiabetogenic Effects of Opuntia dillenii Seed Oil.

Opuntia dillenii (Ker-Gawl.) Haw. is a medicinal plant that is widely used by the Moroccan population to treat many diseases, thanks to its richness in bioactive molecules. This study aims to evaluate the total phenolic content and antioxidant, antihyperlipidemic, and antidiabetogenic activities of O. dillenii seeds oil (ODSO), in vivo. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and the Folin-Ciocalteu method were applied in this study to determine antioxidant activity and total phenolic content of ODSO, respectively. The antihyperlipidemic effect of the ODSO (2 ml/kg) was evaluated in the high-fat diet-fed albino mice, relying on lipid profile, blood glucose, and growth performance variations. Moreover, the preventive effect of ODSO was evaluated against alloxan monohydrate-induced diabetes in albino mice. ODSO had the highest total phenolic content (518.18 ± 14.36 mg EAC/kg) and DPPH scavenging activity (IC50 = 0.38 ± 0.08 mg/mL). Furthermore, ODSO showed a significant antidiabetogenic effect by reducing bodyweight loss, blood sugar level rise, and mortality rate caused by alloxan in albino mice. Then, ODSO has exhibited a significant antihyperlipidemic effect by improving the lipid profile disorder and glucose level rise in the blood, produced by the high-fat diet-fed albino mice. Results suggest that antidiabetogenic and antihyperlipidemic activities of ODSO correlate to the phenolic content and antioxidant activity of this oil. Hence, this plant could be a significant source of medically important critical compounds.

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.

Origanum majorana L. extract exhibit positive cooperative effects on the main mechanisms involved in acute infectious diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L. (Lamiaceae) is commonly used in Moroccan folk medicine to treat infantile colic, abdominal discomfort and diarrhea. Liquid stools and abdominal discomfort observed in acute infectious diarrhea are the consequences of imbalance between intestinal water secretion and absorption in the lumen, and relaxation of smooth muscle surrounding the intestinal mucosa. AIM OF THE STUDY: The objective of our study was to see if aqueous extract of Origanum majorana L. (AEOM) may exhibit an effect on those deleterious mechanisms. MATERIALS AND METHODS: The effect of AEOM on electrogenic Cl- secretion and Na+ absorption, the two main mechanisms underlying water movement in the intestine, was assessed on intestinal pieces of mice intestine mounted, in vitro, in Ussing chambers. AEOM effect on muscle relaxation was measured on rat intestinal smooth muscle mounted in an isotonic transducer. RESULTS: 1) AEOM placed on the serosal (i.e. blood) side of the piece of jejunum entirely inhibited in a concentration-dependent manner the Forskolin-induced electrogenic chloride secretion, with an IC50 = 654 ±â€¯8 µg/mL. 2) AEOM placed on the mucosal (i.e. luminal) side stimulated in a concentration-dependent manner an electrogenic Na+ absorption, with an IC50 = 476.9 ±â€¯1 µg/mL. 3) AEOM (1 mg/mL) inhibition of Forskolin-induced electrogenic secretion was almost entirely prevented by prior exposure to Ca++ channels or neurotransmitters inhibitors. 4) AEOM (1 mg/mL) proabsorptive effect was greater in the ileum and progressively declined in the jejunum, distal colon and proximal colon (minimal). 5) AEOM inhibited in a concentration-dependent manner smooth muscle Carbachol or KCl induced contraction, with an IC50 = 1.64 ±â€¯0.2 mg/mL or 1.92 ±â€¯0.8 mg/mL, respectively. CONCLUSION: the present results indicate that aqueous extract of Origanum majorana L. exhibit positive cooperative effects on the main mechanisms that are involved in acute infectious diarrhea.

Myorelaxant Activity of essential oil from Origanum majorana L. on rat and rabbit.

ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L. (Lamiaceae) was usually used in Moroccan folk medicine to treat infantile colic and abdominal discomfort. MATERIALS AND METHODS: The essential oil from the aerial part of the dry Origanum majorana L. (EOOM) was obtained through hydro distillation and analyzed by gas chromatography/mass spectrometry (GC/MS). The effect of EOOM on muscle relaxation was measured on rabbit and rat intestinal smooth muscle mounted in an isotonic transducer. RESULTS: 1) The main compounds obtained from the aqueous extract of this plant were alpha Terpineol, L-terpinen-4-ol and Beta.-Linalool. 2) EOOM inhibited in a concentration-dependent manner spontaneous contraction of rabbit jejunum, with an IC50 = 64.08 ±â€¯2.42 µg/mL. 3) In rat intestine, EOOM induced the relaxation of the tissue in concentration-dependent manner with an IC50 = 39.70 ±â€¯2.29 µg/mL when the tissue was pre-contracted with CCh 10-6 M, and 48.70 ±â€¯2.26 µg/mL when the tissue was pre-contracted with 25 mM KCl. 4) The relaxation effect induced by EOOM was more important than that obtained in the presence of atropine, hexamethonium, Nifedipine, L-NAME and Blue of methylene. CONCLUSION: the present result indicates that essential oil of Origanum majorana L. exhibit an effect on intestinal relaxation in vitro. This effect further validates the traditional use of Origanum majorana L. to treat infantile colic and abdominal discomfort.

Antidiabetic effect of Opuntia dillenii seed oil on streptozotocin-induced diabetic rats

To assess the antidiabetic effect of Opuntia dillenii seed oil on rats with diabetes mellitus. Methods: A rat diabetes model was established by intraperitoneal injection of rats with 50 mg/kg streptozotocin. Thirty albino Wistar rats were divided into five groups: the diabetic control group and normal control group were treated only with distilled water, two diabetic groups received 1 and 2 mL/kg of oil per day, respectively, for 30 days and one diabetic group received 2 mg/kg of glibenclamide. In addition, blood glucose was determined weekly. Body weight, average daily food, water intake and urinary volume of each animal were determined before and after the treatment period. After the treatment period, hepatic glycogen was determined using the anthrone reagent, and glycosuria, total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, urea, creatinine and uric acid were estimated using common clinical diagnostic kits. Results: Oral intake of the oil at 1 and 2 mL/kg for the diabetic animals significantly diminished blood glucose, glycosuria, total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, urea, creatinine and uric acid, accompanied by a noticeable elevation in the amount of hepatic glycogen in comparison with the diabetic control group. Similarly, Opuntia dillenii seed oil significantly increased the food intake and decreased the urinary volume per day in treated rats of the same groups in comparison with the period before the treatment intervention and attenuated body weight loss in the diabetic rats. Moreover, this effect of the oil was dose dependent. On the other hand, the oil did not affect their need for water. Conclusions: The results show that Opuntia dillenii seed oil has a very important antidiabetic effect on streptozotocin-induced diabetic rats. Hence, we suggest it as a preventive control of diabetes mellitus.

Hepatoprotective effect of Opuntia dillenii seed oil on CCl4 induced acute liver damage in rat

Objective: To investigate the hepatoprotective effect of Opuntia dillenii seed oil (ODSO) on CCl4 provoked liver injury in rat. Methods: Animals were treated orally with ODSO at a concentration of 2 mL/kg, once daily for one week before the first intraperitoneal injection of CCl4, and thereafter the administration of the oil was continued for 7 days until the introduction of the second injection of CCl4. Fourteen hours after the last dose of CCl4, rats were sacrificed, and the relative liver weight, weight gain, alkaline phosphatase, aspartate amino transferase, alanine aminotransferase, direct bilirubin, total bilirubin, triglycerides, total cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, plasmatic glucose, urea, creatinine, acid uric and malondialdehyde were determined. Results: The significant increase was found in relative liver weight and plasma levels of alanine aminotransferase, aspartate amino transferase, alkaline phosphatase, total bilirubin, direct bilirubin, triglycerides, very low-density lipoprotein, urea, uric acid and malondialdehyde. Likewise, the significant decrease was indicated in the weight gain and the level of glucose plasmatic, and high-density lipoprotein levels in CCl4 produced liver injury in rats were re-established to normal levels when treated with ODSO.While, no change was observed in the total cholesterol, low-density lipoprotein and creatinine in all animals. Conclusions: We conclude that the ODSO has a protective effect on CCl4-mediated liver injury. Hence, we suggest its inclusion as a preventive control of liver disorders.

Antihypertensive and vasodilator effects of methanolic extract of Inula viscosa: Biological evaluation and POM analysis of cynarin, chlorogenic acid as potential hypertensive.

BACKGROUND: Inula viscosa L. (Asteraceae) is a medicinal plant widely used as a folk medicine in oriental Morocco, to treat hypertension. The antihypertensive effect of the methanolic extract obtained from I. viscosa leaves was evaluated in hypertensive L-NAME rats. Systolic blood pressure (SBP) was measured using a non-invasive indirect tail-cuff plethysmographic method. Four groups of rats were used: a control group; a hypertensive group treated with L-NAME (32mg/kg/day); a positive control group treated with L-NAME plus enalapril (15mg/kg/day) as a reference antihypertensive agent; and a group treated with L-NAME plus MeOH-extract (40mg/kg/day). METHODS: Treatment with L-NAME alone caused a progressive increase in SBP. After 4 weeks, the value of SBP reached 160±2mmHg which shows the installation of hypertension. Enalapril prevented the increase in SBP, which remained normal at 123±1mmHg after 4 weeks of treatment. The administration of MeOH-extract along with L-NAME prevented the increase in SBP as well, which remained constant at 115±1mmHg after 4 weeks of treatment. In ex-vivo models, MeOH-extract produced a relaxation of pre-contracted ring aorta (54 ± 2% of relaxation at 3g/L). But, when the rings were denuded, MeOH-extract failed to relax pre-contracted rings of aorta. Phytochemical study of I. viscosa MeOH-extract revealed the presence of phenolic compounds, such as cynarin and chlorogenic acid. RESULTS: The present results suggest that I. viscosa MeOH-extract has an antihypertensive, predominantly mediated by an endothelium-dependent vasodilatory effect. Cynarin and chlorogenic acid, which have a strong vasorelaxant effect may be involved in the antihypertensive effect of the plant extract. The bioinformatic POM analysis confirms the therapeutic potential of cynarin and chlorogenic acids as inhibitors of various biotargets. Based on the results, the coordination of these phytochemicals with calcium and transition metals should be studied, for better scope at antihypertensive drug development.

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.