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Objectives: The chemical composition of cactus pear seed oil (Opuntia ficus-indica [L.] Mill.) was analyzed in terms of its fatty acid composition, tocopherol content, phenolic identification, and the oil’s phenolic-rich fraction antioxidant power was determined.Methods : : Fatty acid profiling was performed by gas chromatography coupled to an FI detector. Tocopherols and phenolic compounds were analyzed by LC-FLD/UV, and the oil’s phenolic-rich fraction antioxidant power was determined by phosphomolybdenum, DPPH assay and β-carotene bleaching test.Results : : Fatty acid composition was marked by a high unsaturation level (83.22 ± 0.34%). The predominant fatty acid was linoleic acid (66.79 ± 0.78%), followed by oleic acid (15.16 ± 0.42%) and palmitic acid (12.70 ± 0.03%). The main tocopherol was γ-tocopherol (172.59 ± 7.59 mg/kg. In addition, Tyrosol, vanillic acid, vanillin, ferulic acid, pinoresinol, and cinnamic acid were identified as phenolic compounds in the analyzed seed oil. Moreover, the oil’s phenolics-rich fraction showed a significant total antioxidant activity, scavenged DPPH up to 97.85%, and effectively protected β-carotene against bleaching (97.56%).Conclusion : : The results support the potential use of cactus pear seed oil as a functional food.

BackgroundWith the increasing global prevalence of type 2 diabetes (T2D) and obesity, there is a pressing need for novel therapeutic interventions. Lavandula stoechas, a medicinal plant traditionally used for various ailments, holds promise as a potential agent for T2D management, particularly in Morocco, where it is commonly used to treat diabetes. This study aims to evaluate the pharmacological potential of L. stoechas aqueous extract (AqLs) by assessing its lipase inhibition antioxidant and anti-inflammatory activities, identifying phenolic compounds, and examining its efficacy in reducing diabetic complications.MethodsThe pharmacological potential of L. stoechas aqueous extract was investigated using in vitro assays. The inhibitory effect on pancreatic lipase, antioxidant power (FRAP), and anti-inflammatory activity (albumin denaturation method) was assessed. High-performance liquid chromatography (HPLC) analysis identified phenolic compounds. Additionally, albumin glycation was evaluated by estimating fructosamine, carbonyl groups, and amyloid β-structures to assess efficacy in mitigating diabetic complications.ResultsThe extract demonstrated concentration-dependent inhibition of pancreatic lipase (IC50 = 0.132 ± 0.006 mg/mL), potent antioxidant activity (IC50 = 604.99 ± 1.01 μg/mL), and dose-dependent anti-inflammatory effects (IC50 = 207.01 ± 34.94 mg/mL). HPLC analysis revealed phenolic compounds: naringin (38.28%), syringic acid (25.72%), and cinnamic acid (15.88%) were the most abundant, with 4-hydroxybenzoic acid, hydrated catechin, and catechin ranging from 9.60% to 5.24%, and p-coumaric acid (1.73%). Furthermore, the extract inhibited albumin glycation and fructosamine production, suggesting efficacy in mitigating diabetic complications.ConclusionThese findings highlight the multifaceted pharmacological potential of L. stoechas aqueous extract in T2D management, suggesting that this plant can be highly beneficial for diabetic individuals.

Abstract By analyzing a mouse Interspecific Recombinant Congenic Strain (IRCS), we previously identified a quantitative trait locus (QTL), called Mafq1 on mouse chromosome 1, that is associated with male hypofertility and ultrastructural sperm abnormalities. Within this locus, we identified a new candidate gene that could be implicated in a reproductive phenotype: Tex44 (Testis-expressed protein 44). We thus performed a CRISPR/Cas9-mediated complete deletion of this gene in mice in order to study its function. Tex44-KO males were severely hypofertile in vivo and in vitro due to a drastic reduction of sperm motility which itself resulted from important morphological sperm abnormalities. Namely, Tex44-KO sperm showed a disorganized junction between the midpiece and the principal piece of the flagellum, leading to a 180° flagellar bending in this region. In addition, the loss of some axonemal microtubule doublets and outer dense fibers in the flagellum’s principal piece has been observed. Our results suggest that, in mice, TEX44 is implicated in the correct set-up of the sperm flagellum during spermiogenesis and its absence leads to flagellar abnormalities and consequently to severe male hypofertility. Graphical Abstract

Abstract Duchenne muscular dystrophy is a severe neuromuscular disease causing a progressive muscle wasting due to mutations in the DMD gene that lead to the absence of dystrophin protein. Adeno-associated virus (AAV)-based therapies aiming to restore dystrophin in muscles, by either exon skipping or microdystrophin expression, are very promising. However, the absence of dystrophin induces cellular perturbations that hinder AAV therapy efficiency. We focused here on the impact of the necrosis-regeneration process leading to nuclear centralization in myofiber, a common feature of human myopathies, on AAV transduction efficiency. We generated centronucleated myofibers by cardiotoxin injection in wild-type muscles prior to AAV injection. Intramuscular injections of AAV1 vectors show that transgene expression was drastically reduced in regenerated muscles, even when the AAV injection occurred 10 months post-regeneration. We show also that AAV genomes were not lost from cardiotoxin regenerated muscle and were properly localised in the myofiber nuclei but were less transcribed leading to muscle transduction defect. A similar defect was observed in muscles of the DMD mouse model mdx. Therefore, the regeneration process per se could participate to the AAV-mediated transduction defect observed in dystrophic muscles which may limit AAV-based therapies.

Dominant dynamin 2 (DNM2) mutations are responsible for the autosomal dominant centronuclear myopathy (AD-CNM), a rare progressive neuromuscular disorder ranging from severe neonatal to mild adult forms. We previously demonstrated that mutant-specific RNA interference is an efficient therapeutic strategy to rescue the muscle phenotype at the onset of the symptoms in the AD-CNM knockin-Dnm2R465W/+ mouse model. Our objective was to evaluate the long-term benefit of the treatment along with the disease time course. We demonstrate here that the complete rescue of the muscle phenotype is maintained for at least 1 year after a single injection of adeno-associated virus expressing the mutant-specific short hairpin RNA (shRNA). This was achieved by a maintained reduction of the mutant Dnm2 transcript. Moreover, this long-term study uncovers a pathological accumulation of DNM2 protein occurring with age in the mouse model and prevented by the treatment. Conversely, a physiological DNM2 protein decrease with age was observed in muscles from wild-type mice. Therefore, this study highlights a new potential pathophysiological mechanism linked to mutant protein accumulation and underlines the importance of DNM2 protein expression level for proper muscle function. Overall, these results strengthen the allele-specific silencing approach as a robust, safe, and efficient therapy for AD-CNM.

Context: Ammodaucus leucotrichus commonly known as a ‘Kamune es sufi or akâman’ in Morocco, is used to treat many diseases including diabetes. Aims: To investigate the antihyperglycemic activity of an aqueous extract of fruits A. leucotrichus (AEAL) and its chemical composition. Methods: The antihyperglycemic effect of the AEAL was tested against intestinal α-glucosidase and pancreatic α-amylase activities, in vitro, at the concentrations (41-328 µg/mL) and (0.5-3 mg/mL) respectively. In addition, the inhibitory effect of the AEAL (150 mg/kg) against these enzymes was confirmed, in vivo in normal and alloxan diabetic rats using sucrose, starch, and glucose as a substrate.The antihyperglycemic effect of the AEAL was also tested against intestinal D-glucose absorption activity at the dose of 150 mg/kg using the jejunum segment perfusion technique, in situ. Chemical composition was evaluated using HPLC. Results: The results of this study showed that the AEAL was significantly (p

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

In mammalian fertilization, the link between the oocyte plasma membrane and underneath cytoskeleton has often been associated to key elements of successful gamete fusion, like microvilli shaping or CD9 function, but its effective role has poorly been studied. EWI-2 and EWI-F as cis partners of CD9, and ERM proteins (Ezrin, Radixin and Moesin) that both attach to the actin cytoskeleton and to the EWI are part of the molecules that make the link between the oocyte membrane and its cytoskeleton. This study aims to assay through siRNA inhibition, the involvement of these ERM and EWI molecules in mouse fertilization, their role in the microvilli morphology of the egg but also their possible contribution to the cortical tension, a parameter that reflects the mechanical behavior of the oocyte cortex. Whereas inhibiting separately the expression of each protein had no effect on fertilization, the combined inhibition of either EWI-2/EWI-F or the three ERM triggered a significant decrease of the fertilization index. This inhibition seems to correlate with an increase in the radius of curvature of the oocyte microvilli. It also causes a decrease of the oocyte cortical tension. These results show the importance of EWI-2 and EWI–F and ERM proteins in the smooth running of a fertilization event and support their involvement in the microvilli architecture of the oocyte and in its mechanical properties.

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.

Origanum genus is one of the most widely used herbs in folk medicine for its biological properties. The present investigation aims to characterize, for the first time, endemic Origanum grosii collected from the Taounate region, Morocco. This characterization was realized by determining the concentration of metals in different parts of the plant (flowers, leaves, and stems) by ICP-MS, and the results were studied statistically by Principal Component Analysis (PCA). Phytochemical screening with the dosage of polyphenols and flavonoids has been conducted. To know more about this species, antihyperglycemic tests have been performed to highlight the presence or absence of the antidiabetic effect for this plant. An Oral Glucose Tolerance Test (OGTT) has been performed on normal mice which were divided into two groups of six mice each. Group 1 (control group) was treated with distilled water, and group 2 was treated with an aqueous extract of O. grosii by gavage at 150 mg/kg. Digestive enzyme α-amylase inhibition assay has also been evaluated to study the inhibition effect of the studied extract using acarbose as a control. The results showed that the leaves exhibited a high concentration of trace elements (Ca, Mg, and K) and total absence of heavy metals, which were found in small quantities (Cr, Ni, and B) on the stems, and this makes the plant safe to use. On the other hand, tannins, flavonoids, triterpenes, and steroids were the major families strongly present in this species. The antidiabetic results showed that O. grosii have significantly reduced postprandial hyperglycemia after glucose loading in normal rats. It showed also that this species has a significant antihyperglycemic activity reflected by the inhibition of α-amylase. The one responsible for this property could be the synergy between the trace elements and the nature of the chemical families of O. grosii species, which can make this plant useful in the management of postprandial hyperglycemia.

Objective. In Morocco, Thymelaea hirsuta (T. hirsuta) (Thymelaeacea) is a medicinal plant widely used to treat and prevent diabetes. The present study aimed to evaluate the medium-term antidiabetic effect of aqueous extract (AqTh) and ethyl acetate fraction (EaTh) of Th and to investigate their putative protective effect on pancreatic islet degeneration, diabetic nephropathy, and liver damages in streptozotocin (STZ)-diabetic rats. Methods. Experimental diabetes in rats was induced by a single intraperitoneal injection of 50 mg/kg of STZ. During the treatment period (4 weeks), 200 mg/kg AqTh and 50 mg/kg EaTh were orally administrated daily to STZ-diabetic rats. A group of parameters including fasting blood glucose, biochemical parameters, and intestinal α-glucosidase inhibition were studied. Furthermore, histological study of the pancreas, kidney, liver, and aorta was also realized. Results. At the end of the treatment, both AqTh and EaTh had normalized fasting blood glucose to 1.08 and 1.25 g/l, respectively. AqTh has also reduced urinary creatinine and HbAc1. The EaTh showed inhibitory activity against intestinal α-glucosidase, whereas AqTh did not have this inhibitory effect. Furthermore, pancreas hematoxylin and eosin staining showed that AqTh or EaTh prevents pancreatic islet cell degeneration. As the same kidney, Masson’s trichrome staining has shown a significant prevention of renal fibrosis in AqTh- or EaTh-treated diabetic rats. On the other hand, liver hematoxylin and eosin staining showed that AqTh and EaTh prevent liver damage. Conclusion. We conclude that medium-term administration of AqTh and EaTh exerts significant antihyperglycemic effect in STZ-diabetic rats possibly through intestinal α-glucosidase inhibition and protection against pancreatic islet cell damage. Moreover, AqTh and EaTh treatment prevent nephropathy and liver complications in STZ-diabetic rats.

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.

We assessed the potential of Lmna-mRNA repair by spliceosome-mediated RNA trans-splicing as a therapeutic approach for LMNA-related congenital muscular dystrophy. This gene therapy strategy leads to reduction of mutated transcript expression for the benefit of corresponding wild-type (WT) transcripts. We developed 5′-RNA pre-trans-splicing molecules containing the first five exons of Lmna and targeting intron 5 of Lmna pre-mRNA. Among nine pre-trans-splicing molecules, differing in the targeted sequence in intron 5 and tested in C2C12 myoblasts, three induced trans-splicing events on endogenous Lmna mRNA and confirmed at protein level. Further analyses performed in primary myotubes derived from an LMNA-related congenital muscular dystrophy (L-CMD) mouse model led to a partial rescue of the mutant phenotype. Finally, we tested this approach in vivo using adeno-associated virus (AAV) delivery in newborn mice and showed that trans-splicing events occurred in WT mice 50 days after AAV delivery, although at a low rate. Altogether, while these results provide the first evidence for reprogramming LMNA mRNA in vitro, strategies to improve the rate of trans-splicing events still need to be developed for efficient application of this therapeutic approach in vivo.

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.

Abstract Rapid advances in allele‐specific silencing by RNA interference established a strategy of choice to cure dominant inherited diseases by targeting mutant alleles. We used this strategy for autosomal‐dominant centronuclear myopathy (CNM), a rare neuromuscular disorder without available treatment due to heterozygous mutations in the DNM2 gene encoding Dynamin 2. Allele‐specific siRNA sequences were developed in order to specifically knock down the human and murine DNM2‐mRNA harbouring the p.R465W mutation without affecting the wild‐type allele. Functional restoration was achieved in muscle from a knock‐in mouse model and in patient‐derived fibroblasts, both expressing the most frequently encountered mutation in patients. Restoring either muscle force in a CNM mouse model or DNM2 function in patient‐derived cells is an essential breakthrough towards future gene‐based therapy for dominant centronuclear myopathy.

Caralluma europaea (Guss.) N.E.Br. (C. europaea), is a medicinal plant used traditionally to treat diabetes mellitus (DM) in Morocco. This study aimed to investigate the in vitro antioxidant properties, glucose diffusion effects, α-amylase inhibitory activity, and pancreatic protective effects of C. europaea in experimental alloxan-induced diabetes in mice. Total phenolic contents were determined by Folin–Ciocalteu colorimetric method, total flavonoid contents were measured by aluminum chloride colorimetric assay, and tannins contents were determined by employing the vanillin method. C. europaea ethyl acetate fraction exhibited high antioxidant potential in terms of radical scavenging (DPPH) (IC50 = 0.22 ± 0.01 mg/mL), β-carotene bleaching activity (IC50 = 1.153 ± 0.07 mg/mL), and Ferric-reducing antioxidant power. Glucose diffusion was significantly inhibited by the ethyl acetate fraction at 60,120and 180 min, while the aqueous extract did not have this inhibitory effect when compared with the control group. Potent α-amylase inhibitory activity was observed in the ethyl acetate fraction and the aqueous extract in vitro and in vivo using STZ-diabetic rats. On the other hand, the administration of the ethyl acetate fraction (60 mg/kg) significantly attenuated alloxan-induced death and hyperglycemia in treated mice. Furthermore, histopathological investigations revealed that the ethyl acetate fraction protected islets of Langerhans against alloxan-induced tissue alterations. These results suggest that C. europaea exhibited an important antihyperglycemic effect via the inhibition of glucose diffusion and pancreatic α-amylase activity. In addition, the antidiabetogenic effect of C. europaea might be attributed to their polyphenol and flavonoid compounds, which could be reacted alone, or in synergy, to scavenge the free radicals produced by the alloxan.

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. [ABSTRACT FROM AUTHOR]

Arbutus unedo (A. unedo) is a medicinal plant commonly used to treat hypertension and diabetes in Oriental Morocco. Our previous studies showed that A. unedo has a vascular, diuretic, natriuretic, antiagregant and antidiabetic properties. Our goal was to show the vascular action of two groups of flavonoids (free and heterosidic flavonoids) extracted from the leaves of A. unedo on the isolated aorta of rat. A. unedo leaves were collected from Tazekka Mountain (Morocco). Two flavonoïds-enriched (Genins and Heterosids) and a third final aqueous fractions were obtained using the soxhlet refluxing apparatus and tested in vitro on a phenylephrine-precontracted aorta. Thin layer chromatography analysis of both flavonoïds-enriched fractions was performed with silica gel on an aluminum support. The determination of total polyphenolic was achieved using Folin-Ciocalteu method and the total content of flavonoids was determined by aluminum chloride method. The genins-enriched fraction induced a moderate contraction of aorta while the aqueous fraction caused an opposite effect. The heterosids-enriched fraction induced two distinct effects, a relaxation followed by a contraction of the same amplitude. All these effects are endotheliumdependent but not depending on each another. Moreover, the determination of total polyphenolic and flavonoid contents and thin layer chromatography analysis confirmed the abundance of these compounds in the studied fractions of A. unedo leaves. In conclusion, the vasorelaxant property of aqueous and heterosidic fractions are partly attributed to the presence of the flavonoids compounds. These results confirm the validity of the traditional use of A. unedo in hypertension treatment

Male fertility disorders often have their origin in disturbed spermatogenesis, which can be induced by genetic factors. In this study, we used interspecific recombinant congenic mouse strains (IRCS) to identify genes responsible for male infertility. Using ultrasonography, in vivo and in vitro fertilization (IVF) and electron microscopy, the phenotyping of several IRCS carrying mouse chromosome 1 segments of Mus spretus origin revealed a decrease in the ability of sperm to fertilize. This teratozoospermia included the abnormal anchoring of the acrosome to the nucleus and a persistence of residual bodies at the level of epididymal sperm midpiece. We identified a quantitative trait locus (QTL) responsible for these phenotypes and we have proposed a short list of candidate genes specifically expressed in spermatids. The future functional validation of candidate genes should allow the identification of new genes and mechanisms involved in male infertility.

We have previously shown, using antibodies, that the sperm alpha6beta1 integrin is involved in mouse gamete fusion in vitro. Here we report the conditional knockdown of the sperm Itgb1 gene. It induced a drastic failure of sperm fusogenic ability with sperm accumulation in the perivitelline space of in vitro inseminated oocytes deleted or not for the Itgb1 gene. These data demonstrate that sperm, but not oocyte, beta1 integrin subunit is involved in gamete adhesion/fusion. Curiously, knockdown males were fertile in vivo probably because of the incomplete Cre-mediated deletion of the sperm Itgb1 floxed gene. Indeed, this was shown by Western blot analysis and confirmed by both the viability and litter size of pups obtained by mating partially sperm Itgb1 deleted males with females producing completely deleted Itgb1 oocytes. Because of the total peri-implantation lethality of Itgb1 deletion in mice, we assume that sperm that escaped the Itgb1 excision seemed to be preferentially used to fertilize in vivo. Here, we showed for the first time that the deletion, even partial, of the sperm Itgb1 gene makes the sperm unable to normally fertilize oocytes. However, to elucidate the question of the essentiality of its role during fertilization, further investigations using a mouse expressing a recombinase more effective in male germ cells are necessary.

Thrombocytes, also known as platelets, are crucial in maintaining the balance between blood clotting. Platelet hyperactivity and oxidative stress are the primary factors contributing to cardiovascular complications. Antithrombotic therapy remains one of the most effective treatments, but various potential side effects hinder its effectiveness, including the risk of haemorrhage. Intense research has been conducted on medicinal plants to discover the natural antithrombotic compounds. Argania spinosa, commonly known as the argan tree or argan oil tree, is a native species of southwestern Morocco. This study evaluated the primary and secondary hemostasis and antioxidant activity of leaf and branch aqueous extracts of A. spinosa and also assessed the phytochemical composition of these extracts. Platelet aggregation assay was performed using washed platelets stimulated with thrombin. For plasmatic coagulation, activated partial thromboplastin time and prothrombin time were measured using the poor plasma method. Bleeding time was evaluated by inducing bleeding at the tip of a mouse tail. The antioxidant activity of the extracts was determined through the DPPH, ß-carotene, and FRAP methods. The presence or absence of the secondary metabolites was carried out with the help of specific reagents, and the quantitative analysis was carried out using spectrophotometric and colorimetric methods. The study results revealed the presence of phenols, total flavonoids, cardiac glycosides, tannins, and coumarins type of secondary metabolites in both types of aqueous extracts and a higher concentration of these was recorded in the leaves extracts. Both aqueous extracts significantly reduced in vitro thrombin-induced platelet aggregation, extended tail bleeding time, prolonged activated partial thromboplastin and prothrombin time and exhibited remarkable antioxidant activity. The leaf extract of A. spinosa exerts significant effects against thrombotic manifestations and could be a promising source of new antithrombotic compounds. [ABSTRACT FROM AUTHOR]

Opuntia ficus indica L (Cactaceae), is commonly employed in Morocco as an alternative medicinal approach for managing diabetes mellitus (DM). The objective of the study is to explore and examine novel mechanism underlying the antidiabetic activity of Opuntia ficus indica seed oil (OFIO), which has shown promising potential in managing diabetes, but the exact mechanisms responsible for its antidiabetic effects remain unclear. Therefore, the current study explores the antihyperglycemic effectof OFIO, the in vitro antioxidant properties, and the antiglycation activity of OFIOof hemoglobin (Hb) model. The total phenolic levels were determined using Folin-Ciocalteu colorimetric approach and total flavonoid levels were determined using colorimetric assay with aluminum chloride. The effect of antihyperglycemia was evaluated using the inhibitory effect of pancreatic a-amylase activity both in vitro and in vivo using Alloxan induced-diabetic rats and the glucose uptake in an isolated rat hemidiaphragm in vitro model. The antioxidant activity was studied using the DPPH Radical scavenging activity test. In addition, the antiglycation activity of OFIO was also tested in-vitro using hemoglobin model. The outcomes derived from this research have demonstrated that OFIO exhibited potent a-amylase inhibitory activity in vitro (p < 0.01; IC50 values of 4.24 ±0.18 mg/ml, and 4.05± 0.08 mg/ml respectively) and in vivo using Alloxan induced-diabetic rats. In contrast, OFIO has no effect on glucose uptake by the rat diaphragm muscle as compared to negative control. In addition, OFIO showed a significant antioxidant and hemoglobin antiglycation activities (p<0.001) with an IC50 value of 2.05± 0.06 mg/ml, and 0.485± 0.017 mg/ml, respectively. The findings of this study suggest that is OFIO has promising antidiabetic activity. [ABSTRACT FROM AUTHOR]

Neurotensin (NTS) is a peptide discovered in 1973, which has been studied in many fields and mainly in oncology for its action in tumor growth and proliferation. In this review of the literature, we wanted to focus on its involvement in reproductive functions. NTS participates in an autocrine manner in the mechanisms of ovulation via NTS receptor 3 (NTSR3), present in granulosa cells. Spermatozoa express only its receptors, whereas in the female reproductive system (endometrial and tube epithelia and granulosa cells), we find both NTS secretion and the expression of its receptors. It consistently enhances the acrosome reaction of spermatozoa in mammals in a paracrine manner via its interaction with NTSR1 and NTSR2. Furthermore, previous results on embryonic quality and development are discordant. NTS appears to be involved in the key stages of fertilization and could improve the results of in vitro fertilization, especially through its effect on the acrosomal reaction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A rapid, easy and simple method for the isolation and purification of α-glucosidase inhibitors of the ethyl acetate extract of Thymelaea hirsuta (EaTh) by a combination of thin layer chromatography (TLC) and enzymatic test has been developed. EaTh was demonstrated previously a potent α-glucosidase inhibitory effect. In this study, we developed a simple TLC-enzymatic test (TLC/EZ) combination to isolate α-glucosidase inhibitors present in EaTh.EaTh was extracted by Soxhlet from Thymelaea hirsuta (T. hirsuta). The EaTh was separated on a silica gel column and then on a TLC plate. After TLC separation, the TLC/EZ combination method was applied. α-glucosidase inhibitors were detected directly in the TLC plate using the glucose oxidase peroxidase method (GOD-POD). A good detection of active compounds was obtained in the TLC favoring the TLC/EZ method. Active compounds were then characterized using high performance liquid chromatography-mass spectrometry (HPLC–MS) analysis. The main α-glucosidase inhibitors present in EaTh have a molecular ion [M + H]+ at m/z = 543. This proposed method is suitable for a reliable isolation and purification of α-glucosidase inhibitors present in EaTh. It could be proposed as an interesting alternative of the classical method for the isolation and purification of α-glucosidase inhibitors in plant extracts. [ABSTRACT FROM AUTHOR]