A Review of Antidiabetic Medicinal Plants as a Novel Source of Phosphodiesterase Inhibitors: Future Perspective of New Challenges Against Diabetes Mellitus.

Intracellular glucose concentration plays a crucial role in initiating the molecular secretory process of pancreatic ß-cells through multiple messengers and signaling pathways. Cyclic nucleotides are key physiological regulators that modulate pathway interactions in ß-cells. An increase of cyclic nucleotides is controled by hydrolysed phosphodiesterases (PDEs), which degrades cyclic nucleotides into inactive metabolites. Despite the undeniable therapeutic potential of PDE inhibitors, they are associated with several side effects. The treatment strategy for diabetes based on PDE inhibitors has been proposed for a long time. Hence, the world of natural antidiabetic medicinal plants represents an ideal source of phosphodiesterase inhibitors as a new strategy for developing novel agents to treat diabetes mellitus. This review highlights medicinal plants traditionally used in the treatment of diabetes mellitus that have been proven to have inhibitory effects on PDE activity. The contents of this review were sourced from electronic databases, including Science Direct, PubMed, Springer Link, Web of Science, Scopus, Wiley Online, Scifinder and Google Scholar. These databases were consulted to collect information without any limitation date. After comprehensive literature screening, this paper identified 27 medicinal plants that have been reported to exhibit anti-phosphodiesterase activities. The selection of these plants was based on their traditional uses in the treatment of diabetes mellitus. The review emphasizes the antiphosphodiesterase properties of 31 bioactive components derived from these plant extracts. Many phenolic compounds have been identified as PDE inhibitors: Brazilin, mesozygin, artonin I, chalcomaracin, norartocarpetin, moracin L, moracin M, moracin C, curcumin, gallic acid, caffeic acid, rutin, quercitrin, quercetin, catechin, kaempferol, chlorogenic acid, and ellagic acid. Moreover, smome lignans have reported as PDE inhibitors: (+)-Medioresinol di-O-ß-d-glucopyranoside, (+)- Pinoresinol di-O-ß-d-glucopyranoside, (+)-Pinoresinol-4-O-ß-d-glucopyranosyl (1→6)-ß-dglucopyranoside, Liriodendrin, (+)-Pinoresinol 4'-O-ß-d-glucopyranoside, and forsythin. This review provides a promising starting point of medicinal plants, which could be further studied for the development of natural phosphodiesterase inhibitors to treat diabetes mellitus. Therefore, it is important to consider clinical studies for the identification of new targets for the treatment of diabetes.

Exploring the Multi-Faceted Potential of Carob (Ceratonia siliqua var. Rahma) Leaves from Morocco: A Comprehensive Analysis of Polyphenols Profile, Antimicrobial Activity, Cytotoxicity against Breast Cancer Cell Lines, and Genotoxicity.

The botanical species Ceratonia siliqua L., commonly referred to as the Carob tree, and locally as "L'Kharrûb", holds significance as an agro-sylvo-pastoral species, and is traditionally utilized in Morocco for treating a variety of ailments. This current investigation aims to ascertain the antioxidant, antimicrobial, and cytotoxic properties of the ethanolic extract of C. siliqua leaves (CSEE). Initially, we analyzed the chemical composition of CSEE through high-performance liquid chromatography with Diode-Array Detection (HPLC-DAD). Subsequently, we conducted various assessments, including DPPH scavenging capacity, ß-carotene bleaching assay, ABTS scavenging, and total antioxidant capacity assays to evaluate the antioxidant activity of the extract. In this study, we investigated the antimicrobial properties of CSEE against five bacterial strains (two gram-positive, Staphylococcus aureus, and Enterococcus faecalis; and three gram-negative bacteria, Escherichia coli, Escherichia vekanda, and Pseudomonas aeruginosa) and two fungi (Candida albicans, and Geotrichum candidum). Additionally, we evaluated the cytotoxicity of CSEE on three human breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-436) and assessed the potential genotoxicity of the extract using the comet assay. Through HPLC-DAD analysis, we determined that phenolic acids and flavonoids were the primary constituents of the CSEE extract. The results of the DPPH test indicated a potent scavenging capacity of the extract with an IC50 of 302.78 ± 7.55 µg/mL, which was comparable to that of ascorbic acid with an IC50 of 260.24 ± 6.45 µg/mL. Similarly, the ß-carotene test demonstrated an IC50 of 352.06 ± 12.16 µg/mL, signifying the extract's potential to inhibit oxidative damage. The ABTS assay revealed IC50 values of 48.13 ± 3.66 TE µmol/mL, indicating a strong ability of CSEE to scavenge ABTS radicals, and the TAC assay demonstrated an IC50 value of 165 ± 7.66 µg AAE/mg. The results suggest that the CSEE extract had potent antioxidant activity. Regarding its antimicrobial activity, the CSEE extract was effective against all five tested bacterial strains, indicating its broad-spectrum antibacterial properties. However, it only showed moderate activity against the two tested fungal strains, suggesting it may not be as effective against fungi. The CSEE exhibited a noteworthy dose-dependent inhibitory activity against all the tested tumor cell lines in vitro. The extract did not induce DNA damage at the concentrations of 6.25, 12.5, 25, and 50 µg/mL, as assessed by the comet assay. However, the 100 µg/mL concentration of CSEE resulted in a significant genotoxic effect compared to the negative control. A computational analysis was conducted to determine the physicochemical and pharmacokinetic characteristics of the constituent molecules present in the extract. The Prediction of Activity Spectra of Substances (PASS) test was employed to forecast the potential biological activities of these molecules. Additionally, the toxicity of the molecules was evaluated using the Protox II webserver.

Chemical Composition, Antioxidant, Anti-Diabetic, Anti-Acetylcholinesterase, Anti-Inflammatory, and Antimicrobial Properties of Arbutus unedo L. and Laurus nobilis L. Essential Oils.

The objectives of this work were to determine the phytochemical composition and antioxidant, anti-diabetic, antibacterial, anti-inflammatory, and anti-acetylcholinesterase properties of Arbutus unedo L. and Laurus nobilis L. EOs. The antioxidant effects were estimated using four complementary methods. In addition, the anti-diabetic activity was assessed by targeting three carbohydrate-hydrolyzing enzymes, namely α-amylase, α-glucosidase, and lipase. The anti-inflammatory and anti-acetylcholinesterase effects were evaluated by testing the inhibitory potential of both plants on lipo-oxygenase and acetylcholinesterase (AChE), respectively. The antimicrobial activity of these oils was evaluated using disc-diffusion, minimum inhibitory concentration (MIC), and minimum lethal concentration (MLC) tests. The chemical composition of L. nobilis essential oil (EO) was dominated by eucalyptol (36.40%), followed by α-terpineole (13.05%), α-terpinyl acetate (10.61%), linalool (10.34%), and northujane (5.74%). The main volatile compounds of A. unedo EOs were decenal (13.47%), α-terpineol (7.8%), and palmitic acid (6.00%). L. nobilis and A. unedo EOs inhibited α-amylase with IC50 values of 42.51 ± 0.012 and 102 ± 0.06 µg/mL, respectively. Moreover, both oils inhibited the activity of α-glucosidase (IC50 = 1.347 ± 0.021 µg/mL and IC50 = 76 ± 0.021 µg/mL) and lipase (IC50 = 21.23 ± 0.021 µg/mL and IC50 = 97.018 ± 0.012 µg/mL, respectively). In addition, L. nobilis EO showed an anti-AChE activity (IC50 = 89.44 ± 0.07 µg/mL) higher than that of A. unedo EO (IC50 = 378.57 ± 0.05 µg/mL). Regarding anti-inflammatory activity, in vitro assays showed that L. nobilis significantly inhibits (IC50 = 48.31 ± 0.07 µg/mL) 5-lipoxygenase compared to A. unedo (IC50 = 86.14 ± 0.05 µg/mL). This was confirmed in vivo via a notable inhibition of inflammation recorded after 6 h of treatment in both plants at a dose of 50 mg/kg. The microbiological results revealed that EOs from both plants inhibited the growth of all tested organisms except P. aeruginosa, with the highest antimicrobial effect for L. nobilis. The results of these tests showed that these two plants possess remarkable biological and pharmacological properties, explaining their medicinal effects and suggesting them as promising sources of natural drugs.

Chemical Composition and Antioxidant, Antimicrobial, and Anti-Inflammatory Properties of Origanum compactum Benth Essential Oils from Two Regions: In Vitro and In Vivo Evidence and In Silico Molecular Investigations.

The purposes of this investigatory study were to determine the chemical composition of the essential oils (EOs) of Origanum compactum from two Moroccan regions (Boulemane and Taounate), as well as the evaluation of their biological effects. Determining EOs' chemical composition was performed by a gas chromatography-mass spectrophotometer (GC-MS). The antioxidant activity of EOs was evaluated using free radical scavenging ability (DPPH method), fluorescence recovery after photobleaching (FRAP), and lipid peroxidation inhibition assays. The anti-inflammatory effect was assessed in vitro using the 5-lipoxygenase (5-LOX) inhibition test and in vivo using the carrageenan-induced paw edema model. Finally, the antibacterial effect was evaluated against several strains using the disk-diffusion assay and the micro-dilution method. The chemical constituent of O. compactum EO (OCEO) from the Boulemane zone is dominated by carvacrol (45.80%), thymol (18.86%), and α-pinene (13.43%). However, OCEO from the Taounate zone is rich in 3-carene (19.56%), thymol (12.98%), and o-cymene (11.16%). OCEO from Taounate showed higher antioxidant activity than EO from Boulemane. Nevertheless, EO from Boulemane considerably inhibited 5-LOX (IC50 = 0.68 ± 0.02 µg/mL) compared to EO from Taounate (IC50 = 1.33 ± 0.01 µg/mL). A similar result was obtained for tyrosinase inhibition with Boulemane EO and Taounate EO, which gave IC50s of 27.51 ± 0.03 µg/mL and 41.83 ± 0.01 µg/mL, respectively. The in vivo anti-inflammatory test showed promising effects; both EOs inhibit and reduce inflammation in mice. For antibacterial activity, both EOs were found to be significantly active against all strains tested in the disk-diffusion test, but O. compactum EO from the Boulemane region showed the highest activity. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for O. compactum EO from the Boulemane region ranged from 0.06 to 0.25% (v/v) and from 0.15 to 0.21% (v/v) for O. compactum from the Taounate region. The MBC/MIC index revealed that both EOs exhibited remarkable bactericidal effects.

Phytochemical Variability, In Vitro and In Vivo Biological Investigations, and In Silico Antibacterial Mechanisms of Mentha piperita Essential Oils Collected from Two Different Regions in Morocco.

The objective of this work is to explore the phytochemical profile of Mentha piperita essential oils (MPEO) collected from two different Moroccan regions using gas chromatography-mass spectrophotometer (GC-MS) and to investigate their antioxidant, anti-inflammatory, antidiabetic and, antimicrobial effects using in vivo and in vitro assays. The chemical constituent of MPEO from the Azrou zone is dominated by carvone (70.25%), while MPEO from the Ouazzane zone is rich in Menthol (43.32%) and Menthone (29.4%). MPEO from Ouezzane showed higher antioxidant activity than EO from Azrou. Nevertheless, EO from Ouezzane considerably inhibited 5-Lipoxygenase (IC50 = 11.64 ± 0.02 µg/mL) compared to EO from Azro (IC50 = 23.84 ± 0.03 µg/mL). Both EOs from Azrou and Ouazzane inhibited the α-amylase activity in vitro, with IC50 values of 131.62 ± 0.01 µg/mL and 91.64 ± 0.03 µg/mL, respectively. The EOs were also tested for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The discdiffusion test revealed that MPEOs from both regions have significant antibacterial efficacy, and MPEOs from the north region showed the highest effect. The gram-positive bacteria were the most susceptible organisms. The MIC concentrations were in the range of 0.05 to 6.25 mg/mL, and the MBC concentrations were within 0.05-25.0 mg/mL. The MBC/MIC index indicated that MPEO has strong bactericidal effects.

LC-MS/MS Phytochemical Profiling, Antioxidant Activity, and Cytotoxicity of the Ethanolic Extract of Atriplex halimus L. against Breast Cancer Cell Lines: Computational Studies and Experimental Validation.

Atriplex halimus L., also known as Mediterranean saltbush, and locally as "Lgtef", an halophytic shrub, is used extensively to treat a wide variety of ailments in Morocco. The present study was undertaken to determine the antioxidant activity and cytotoxicity of the ethanolic extract of A. halimus leaves (AHEE). We first determined the phytochemical composition of AHEE using a liquid chromatography (LC)-tandem mass spectrometry (MS/MS) technique. The antioxidant activity was evaluated using different methods including DPPH scavenging capacity, ß-carotene bleaching assay, ABTS scavenging, iron chelation, and the total antioxidant capacity assays. Cytotoxicity was investigated against human cancer breast cells lines MCF-7 and MDA-MB-231. The results showed that the components of the extract are composed of phenolic acids and flavonoids. The DPPH test showed strong scavenging capacity for the leaf extract (IC50 of 0.36 ± 0.05 mg/mL) in comparison to ascorbic acid (IC50 of 0.19 ± 0.02 mg/mL). The ß-carotene test determined an IC50 of 2.91 ± 0.14 mg/mL. The IC50 values of ABTS, iron chelation, and TAC tests were 44.10 ± 2.92 TE µmol/mL, 27.40 ± 1.46 mg/mL, and 124 ± 1.27 µg AAE/mg, respectively. In vitro, the AHE extract showed significant inhibitory activity in all tested tumor cell lines, and the inhibition activity was found in a dose-dependent manner. Furthermore, computational techniques such as molecular docking and ADMET analysis were used in this work. Moreover, the physicochemical parameters related to the compounds' pharmacokinetic indicators were evaluated, including absorption, distribution, metabolism, excretion, and toxicity prediction (Pro-Tox II).

In Vitro Antioxidant Properties, Glucose-Diffusion Effects, α-Amylase Inhibitory Activity, and Antidiabetogenic Effects of C. Europaea Extracts in Experimental Animals.

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), ß-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.

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.

Inventory of Medicinal Plants Used Traditionally to Manage Kidney Diseases in North-Eastern Morocco: Ethnobotanical Fieldwork and Pharmacological Evidence.

Kidney disease is one of the most common health problems and kidney failure can be fatal. It is one of the health disorders associated with extreme pain and discomfort in patients. In developing countries, such as Morocco where socioeconomic and sanitary conditions are precarious, medicinal plants are considered the primary source of medication. In the present work an ethnobotanical survey was conducted in a remote area of North-Eastern Morocco and we focused on (1) establishing a record of medicinal plants used traditionally by local people to treat kidney diseases and (2) correlate the obtained ethnomedical use with well-studied pharmacological evidence. From February 2018 to January2020, information was gathered from 488 informants using semi-structured questionnaires. The data were analyzed using three quantitative indices: The use value (UV), family use value (FUV), and informant consensus factor (ICF). A total of 121 plant species belonging to 57 botanical families were identified to treat kidney diseases. The families most represented were Asteraceae (14 species), followed by Lamiaceae (12 species) and Apiaceae (10 species). The most commonly used plant parts were leaves, followed by the whole plant and they were most commonly prepared by decoction and infusion. The highest value of the (UV) index was attributed to Herniaria hirsuta L. (UV = 0.16), and the highest family use value (FUV) was assigned to Caryophyllaceae with (FUV = 0.163). Regarding the informant consensus factor (ICF), this index's highest values were recorded for kidney stones (ICF = 0.72). The use of 45% of the selected plants were validated based on literature review. This study helped document and preserve crucial traditional plant knowledge of 121 plant species used to treat kidney problems that can be used in the search for new biologically active compounds through more upcoming pharmacological studies.

Determination of Phenolic Compounds in Various Propolis Samples Collected from an African and an Asian Region and Their Impact on Antioxidant and Antibacterial Activities.

The biological activities of propolis samples are the result of many bioactive compounds present in the propolis. The aim of the present study was to determine the various chemical compounds of some selected propolis samples collected from Palestine and Morocco by the High-Performance Liquid Chromatography-Photodiode Array Detection (HPLC-PDA) method, as well as the antioxidant and antibacterial activities of this bee product. The chemical analysis of propolis samples by HPLC-PDA shows the cinnamic acid content in the Palestinian sample is higher compared to that in Moroccan propolis. The results of antioxidant activity demonstrated an important free radical scavenging activity (2,2-Diphenyl-1-picrylhydrazyl (DPPH); 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and reducing power assays) with EC50 values ranging between 0.02 ± 0.001 and 0.14 ± 0.01 mg/mL. Additionally, all tested propolis samples possessed a moderate antibacterial activity against bacterial strains. Notably, Minimum Inhibitory Concentrations (MICs) values ranged from 0.31 to 2.50 mg/mL for Gram-negative bacterial strains and from 0.09 to 0.125 mg/mL for Gram-positive bacterial strains. The S2 sample from Morocco and the S4 sample from Palestine had the highest content of polyphenol level. Thus, the strong antioxidant and antibacterial properties were apparently due to the high total phenolic and flavone/flavonol contents in the samples. As a conclusion, the activities of propolis samples collected from both countries are similar, while the cinnamic acid in the Palestinian samples was more than that of the Moroccan samples.

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.

Phytochemical Screening, Antioxidant and Antibacterial Activities of Pollen Extracts from Micromeria fruticosa, Achillea fragrantissima, and Phoenix dactylifera.

Pollen is a male flower gametophyte located in the anthers of stamens in angiosperms and a considerable source of compounds with health protective potential. In the present work, phytochemical screening was carried out as well as analysis of the antioxidant and antibacterial properties of pollen extracts from Micromeria fruticosa, Achillea fragrantissima, and Phoenix dactylifera growing wild in Palestine. Phytochemical screening examined the total flavonol, flavone and phenolic content. The DPPH (1,2-Diphenyl-1-Picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods were used to assess antioxidant propriety, and disc diffusion, minimum inhibitory and bactericidal concentration tests were used to test the pollen extract's antibacterial activity against multidrug-resistant (MDR) clinical isolates. The highest level of total phenolic was found in the extract of Micromeria fruticosa (56.78 ± 0.49 mg GAE (Gallic Acid Equivalent)/g). The flavone and flavonol content of samples ranged from 2.48 ± 0.05 to 8.03 ± 0.01 mg QE (Quercetin Equivalent)/g. Micromeria fruticosa pollen with IC50 values of 0.047 and 0.039 mg/mL in the DPPH and FRAP assays, respectively, showed the greatest radical scavenging action. In addition, this pollen showed a mild antibacterial action against the microorganisms studied, with MICs varying from 0.625 to 10 mg/mL and inhibition diameters ranging from 13.66 ± 1.5 to 16.33 ± 1.5 mm.

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.

Caralluma europaea (Guss) N.E.Br.: A review on ethnomedicinal uses, phytochemistry, pharmacological activities, and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Caralluma europaea (Guss) N.E.Br. (Apocynaceae), is a medicinal plant distributed in Morocco, Algeria, Tunisia, Libya, Egypt, Jordan, Spain, and Italy. The different parts of the plant are used traditionally to treat various diseases such as diabetes mellitus, flu, caught, kidney stones, cysts, respiratory infection, cancer, digestives disorders, urogenital infections, metabolic disorders, and cardiovascular problems. AIM OF THE REVIEW: In this review, previous reports on C. europaea concerning its morphological description, geographical distribution, ethnomedicinal uses, phytochemistry, pharmacological properties, and toxicological studies were critically summarized. MATERIALS AND METHODS: A systematic review of the literature on C. europaea was performed by searching the scientific databases Science Direct, PubMed, Scopus, and Google Scholar. RESULTS: In traditional medicine, C. europaea used to treat several illnesses including diabetes, cancer, and kidney stones. Our analysis of the previous reports confirmed the scientific evidence of C. europaea ethnomedicinal uses, especially the antidiabetic activity. However, there was no clear correlation between previous pharmacological reports on C. europaea and its other ethnomedicinal uses in the treatment of kidney stones, flu, caught, metabolic, digestive, cardiovascular and respiratory disorders. The essential oils and extracts of C. europaea exhibited several in vitro and in vivo pharmacological properties such as antidiabetic, antioxidant, anti-inflammatory, analgesic, anti-proliferative, antibacterial, antimicrobial, toxicological, and immunomodulatory effects. Phytochemical characterization of C. europaea revealed the presence of several classes of secondary metabolites such as terpenoids, polyphenols, and flavonoids compounds. Finally, the food preservative ability of the extracts and essential oil obtained from C. europaea has been fully discussed. CONCLUSION: Ethnomedicinal surveys indicated the use of C. europaea for the treatment of numerous diseases. Pharmacological reports showed that C. europaea exhibited significant antidiabetic, antioxidant, anti-inflammatory, analgesic, anti-proliferative, antibacterial, antimicrobial, and immunomodulatory effects. Further studies on the phytochemistry of bioactive compounds should be performed by using bioactivity-guided isolation strategy and improve their biological potency as well as scientific exploitation of traditional uses. An in-depth investigation is needed to valid the food preservative properties.

Anacyclus pyrethrum var. pyrethrum (L.) and Anacyclus pyrethrum var. depressus (Ball) Maire: Correlation between Total Phenolic and Flavonoid Contents with Antioxidant and Antimicrobial Activities of Chemically Characterized Extracts.

In this work, two varieties of Anacyclus pyrethrum (L.) including Anacyclus pyrethrum var. pyrethrum (L.) and Anacyclus pyrethrum var. depressus (Ball) Maire were evaluated for their mineral and chemical compositions, total phenolic and flavonoid contents, and antimicrobial and antioxidant activities using hydroalcoholic extracts from their different parts (leaves, capitula, roots, and seeds). The phytochemical and mineral compositions were carried out using standard methods. The antioxidant activity was determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2-azino-bis 3-ethylbenzothiazolin-6-sulfonic acid), and FRAP (ferric reducing antioxidant power) tests. The antimicrobial activity was assayed using the agar diffusion, minimum inhibitory concentration, and minimum bactericidal concentration methods. The results of the chemical analysis showed that both varieties contained interesting mineral and chemical compositions with potentially active compounds; among them, N-isobutyl-2,4-heptadiene-6-monoynamide and cinnamic acid were detected in the Anacyclus pyrethrum var. pyrethrum (L.) only while thiadiazolo [5,4-d] pyrimidin-7-amine and N-isobutyl-2,4-undecadiene-8,10-diynamide compounds were limited to the Anacyclus pyrethrum var. depressus (Ball) Maire. In vitro antioxidant and antimicrobial activities of the two varieties demonstrated that the different parts had prominent antioxidant and antimicrobial properties. The principal component analysis (PCA) showed great similarity in the activity of the leaves, capitula, and seeds of both plants and a high difference in roots. Anacyclus pyrethrum var. pyrethrum roots were characterized by a high content in phenols and flavonoids and better antibacterial activities compared to Anacyclus pyrethrum var. depressus (Ball) Maire roots, which were characterized by better antioxidant activities. From this study, it can be concluded that the two varieties of Anacyclus pyrethrum (L.) showed promising mineral and chemical compositions with antioxidant and antimicrobial properties.

Medicinal Plants as a Drug Alternative Source for the Antigout Therapy in Morocco.

BACKGROUND: The gout is a metabolic disease that is associated with a high level of uric acid in the blood. This disease is treated with some medications that aim to reduce serum urate levels. However, the use of various medicines leads to the appearance of some side effects, hence the importance of using other treatments based on natural resources. OBJECTIVE: This study presents some medical treatments, their side effects, and some plants that are used for gout management in Morocco in the aim to valorize them. METHODS: We have been consulting various English publications in PubMed, Web of Science, and ScienceDirect published between 1991 and 2019 using the following keywords "drugs," "gout," "Morocco," "medicinal plants," "in vitro," and "in vivo" terms. Then, we have classified the medicines, according to their action mechanisms, and we have cited some species that were reported in Moroccan pharmacopeia as antigout. RESULTS: Three methods of the gout medical management were cited in this work: xanthine oxidase inhibitors, uric acid excretion enhancer, and uricase recombinant. However, it was found that these treatments had various side effects. We have described 23 species, and some of them showed experimentally an antigout effect by blocking the "xanthine oxidase" enzyme. These plants belong to 11 families. Lamiaceae represents the most dominant family with six species followed by Asteraceae with two species. Colchicine isolated from Colchicum autumnale is the most known compound for its efficiency towards gout. CONCLUSION: This work summarized different treatments particularly medicinal plants that are used in Morocco to treat gout disease by blocking uric acid secretion. However, several studies are needed to valorize these antigout natural sources.

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.

The Pathogenesis of Coronavirus Disease 2019 (COVID-19): Evaluation and Prevention.

Coronavirus Disease 2019 (COVID-19) has become a major health problem causing severe acute respiratory illness in humans. It has spread rapidly around the globe since its first identification in Wuhan, China, in December 2019. The causative virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the World Health Organization (WHO) named the new epidemic disease Coronavirus Disease (COVID-19). The incidence of COVID-19 continues to increase with more than three million confirmed cases and over 244,000 deaths worldwide. There is currently no specific treatment or vaccine against COVID-19. Therefore, in the absence of pharmaceutical interventions, the implementation of precautions and hygienic measures will be essential to control and to minimize human transmission of the virus. In this review, we highlight the epidemiology, transmission, symptoms, and treatment of this disease, as well as future strategies to manage the spread of this fatal coronavirus.

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.

Inhibition of α-Glucosidase, Intestinal Glucose Absorption, and Antidiabetic Properties by Caralluma europaea.

Many medicinal plants around the world are used for therapeutic purposes against several diseases, including diabetes mellitus. Due to their composition of natural substances that are effective and do not represent side effects for users, unlike synthetic drugs, in this study, we investigated the inhibitory effect of Caralluma europaea (CE) on α-glucosidase activity in vitro; then the kinetics of the enzyme were studied with increasing concentrations of sucrose in order to determine the inhibition type of the enzyme. In addition, this effect of Caralluma europaea (CE) was confirmed in vivo using rats as an experimental animal model. Among the five fractions of CE, only the ethyl acetate fraction of C. europaea (EACe) induced a significant inhibition of α-glucosidase and its inhibition mode was competitive. The in vivo studies were conducted on mice and rats using glucose and sucrose as a substrate, respectively, to determine the oral glucose tolerance test (OGTT). The results obtained showed that the EACe and the aqueous extract of C. europaea (AECe) have significantly reduced the postprandial hyperglycemia after sucrose and glucose loading in normal and diabetic rats. AECe, also, significantly decreased intestinal glucose absorption, in situ. The results obtained showed that Caralluma europaea has a significant antihyperglycemic activity, which could be due to the inhibition of α-glucosidase activity and enteric absorption of glucose.