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Background: With 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., Methods: The 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., Results: The extract demonstrated concentration-dependent inhibition of pancreatic lipase (IC 50 = 0.132 ± 0.006 mg/mL), potent antioxidant activity (IC 50 = 604.99 ± 1.01 μg/mL), and dose-dependent anti-inflammatory effects (IC 50 = 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., Conclusion: These 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elrherabi, Abdnim, Loukili, Laftouhi, Lafdil, Bouhrim, Mothana, Noman, Eto, Ziyyat, Mekhfi, Legssyer and Bnouham.)

Ceratonia siliqua L. is a medicinal plant that has long been used in traditional Moroccan medicine to treat many diseases. This study aimed to assess the impact of the stages of the immature phase of carob pulp (M1, M2, M3, M4, and M5) on phytochemical composition, antioxidant activity, and antidiabetic activity of Ceratonia siliqua L. The identification of the phenolic profile by HPLC-UV/MS-MS and the study of the antidiabetic effect by in silico, in vitro, and in vivo studies were carried out for extracts with high contents of phenolic compounds from immature wild carob pulp from the communes of Timoulit (TM), Bin Elouidane (AW), and Ouaouizerth (TG) in the province of Azilal in the Béni Mellal-Khénifra region. The results revealed a gradual increase in total sugar content over the pulp's ripening period, reaching a value of 2134 ± 56.23 mg GE/100 g fresh weight (FW) for TG. The three locations showed peak values for total polyphenol content (TPC), total flavonoid content (TFC), and total condensed tannin (TCT) at the M2 stage. AW had the highest concentrations of TPC (3819 ± 226.4 mg GAE/100 g FM), TFC (1034 ± 57.08 mg QE/100 g FM), and TCT (1472 ± 28.46 mg CE/100 g FM). The DPPH assay (7892 ± 296.1 mg TE/100 g FM) and the FRAP assay (278.2 ± 7.85 mg TE/100 g FM) both demonstrated that the TG zone is a highly potent antioxidant zone. In contrast, the AW site exhibited a markedly elevated value of 725.4 ± 103.6 mg TE/100 g FM in the ABTS assay. HPLC-UV-MS/MS analysis showed that the methanolic extracts of immature carob pulp (MEICP) from the three areas contained several different chemical compounds. The most prevalent were 3-O-p-coumaroyl-5-O-caffeoylquinic acid, quercetin 3-methyl ether, gallic acid, and galloylquinic acid. Immature carob pulp extract (ICPE) from AW showed the strongest in vitro inhibition of pancreatic α-amylase (IC 50 = 0.405 µg/mL) and TG extracts were most potent against intestinal α-glucosidase (IC 50 = 0.063 µg/mL). In vivo, AW, TG, and TM extracts significantly reduced postprandial glycemia in rats, with AW having the greatest effect. These results highlight the antidiabetic potential of ICPE. The 3-O-p-Coumaroyl-5-O-caffeoylquinic acid showed better affinity for α-amylase compared to acarbose and interacted significantly with several amino acid residues of the enzyme. Similarly, this molecule and 3,4-Dicaffeoylquinic acid demonstrated a strong affinity for α-glucosidase, suggesting their potential as natural inhibitors of enzymes involved in carbohydrate metabolism. Most of the compounds are not substrates of P-glycoprotein and exhibited high intestinal absorption. Furthermore, the majority of these compounds did not act as inhibitors or substrates of CYP450 enzymes, reinforcing their suitability for development as oral medications. These results underscore the potential of immature carob pulp as a promising antidiabetic agent.

Introduction: Liver diseases represent a significant global health challenge, with primary causes including excessive alcohol consumption, infections, chemotherapy, and autoimmune disorders. Medicinal plants, due to their natural bioactive compounds, hold promise for developing effective treatments and preventive measures against liver ailments. This study aimed to document the use of herbal remedies in northeastern Morocco for liver diseases and correlate these uses with scientific evidence through a bibliometric analysis., Methods: An ethnobotanical survey was conducted in remote communities of northeastern Morocco from October 2020 to January 2022. A total of 189 informants were interviewed using semi-structured questionnaires to gather information on local medicinal plants used for liver ailments. The data were analyzed using four ethnobotanical quantitative indices: use value (UV), familial use value (FUV), informant consensus factor (ICF), and fidelity level (FL). Additionally, a bibliometric analysis was performed to evaluate the scientific support for the ethnopharmacological uses documented., Results: The survey identified 45 plant species from 26 different families used in the treatment of liver diseases. The most frequently utilized species were Cuminum cyminum L. (UV = 0.1065), Allium sativum L. (UV = 0.1015), Salvia officinalis L. (UV = 0.0761), Asparagus officinalis L. (UV = 0.0558), and Ziziphus lotus (L.) Lam. (UV = 0.0457). The Apiaceae family showed the highest familial use value (FUV = 0.1066), followed by Alliaceae (FUV = 0.1015). Liver congestion had the highest informant consensus factor (ICF = 0.83), followed by hepatic colic (ICF = 0.80). Bibliometric analysis revealed that 61% of the plants identified had documented pharmacological effects related to liver health., Discussion: The study demonstrates that traditional knowledge in northeastern Morocco encompasses a rich diversity of medicinal plants used to treat liver diseases. The high ICF values indicate a strong consensus among informants on the efficacy of these remedies. The correlation between ethnopharmacological use and scientific validation for a significant portion of these plants suggests their potential as reliable therapeutic agents for liver conditions. However, further scientific investigations are necessary to confirm their efficacy and safety in clinical settings. This research contributes valuable information for future studies on the therapeutic potential of these plants., Conclusion: This ethnobotanical survey provides a comprehensive database of medicinal plants used in northeastern Morocco for liver diseases. The findings highlight the potential of these plants in developing novel treatments for hepatic conditions, although further research is essential to substantiate their therapeutic claims., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bencheikh, Elbouzidi, Baraich, Bouhrim, Azeroual, Addi, Mothana, Al-Yousef, Eto and Elachouri.)

Glyphosate-based Herbicide (GBH) is a widely used pesticide that functions as a broad-spectrum, non-selective herbicide. Despite advanced research to describe the neurotoxic potential of GBH, the harmful effects on maternal behavior and neurodevelopment of offspring remain unclear. This study was conducted to highlight the effects of GBH on the antioxidant system, anxiety traits, social interaction, and cognitive and sensorimotor functions in pups exposed to 25 or 50 mg/l daily via their mother's milk. Concerning the biochemical biomarkers, GBH administered during the early stages of development negatively affected the status of antioxidant enzymes and lipid peroxidation in the brain structures of the pups. Furthermore, our results showed a significant decrease in acetylcholinesterase (AChE) specific activity within the brains of treated pups. The results of the behavioral tests indicated that the treated offspring developed anxiety, memory, and sociability disorders, as evidenced by the Open Field, Y-maze, object recognition task, and social interaction tests. Through neurodevelopmental testing, we also showed sensorimotor impairment (righting reflex and negative geotaxis) and abnormal maternal behavior. Altogether, our study clearly demonstrates that the developing brain is sensitive to GBH., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin-3-one derivatives 5a - 5o . The synthesis method involves a double 1,3-dipolar cycloaddition reaction following a "click chemistry" approach, starting from the respective [1,4]-benzoxazin-3-ones. Additionally, the study aims to evaluate the antidiabetic potential of these newly synthesized compounds through in silico methods. This synthesis approach allows for the combination of three heterocyclic components: [1,4]-benzoxazin-3-one, 1,2,3-triazole, and isoxazoline, known for their diverse biological activities. The synthesis procedure involved a two-step process. Firstly, a 1,3-dipolar cycloaddition reaction was performed involving the propargylic moiety linked to the [1,4]-benzoxazin-3-one and the allylic azide. Secondly, a second cycloaddition reaction was conducted using the product from the first step, containing the allylic part and an oxime. The synthesized compounds were thoroughly characterized using spectroscopic methods, including 1 H NMR, 13 C NMR, DEPT-135, and IR. This molecular docking method revealed a promising antidiabetic potential of the synthesized compounds, particularly against two key diabetes-related enzymes: pancreatic α-amylase, with the two synthetic molecules 5a and 5o showing the highest affinity values of 9.2 and 9.1 kcal/mol, respectively, and intestinal α-glucosidase, with the two synthetic molecules 5n and 5e showing the highest affinity values of -9.9 and -9.6 kcal/mol, respectively. Indeed, the synthesized compounds have shown significant potential as antidiabetic agents, as indicated by molecular docking studies against the enzymes α-amylase and α-glucosidase. Additionally, ADME analyses have revealed that all the synthetic compounds examined in our study demonstrate high intestinal absorption, meet Lipinski's criteria, and fall within the required range for oral bioavailability, indicating their potential suitability for oral drug development.

Ethnopharmacological Relevance: Olea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine)., Aim of the Study: The primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine., Materials and Methods: In vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days., Results: Aqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects., Conclusion: This study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although giant fennel is recognized as a "superfood" rich in phytochemicals with antioxidant activity, research into the antibacterial properties of its fruits has been relatively limited, compared to studies involving the root and aerial parts of the plant. In this study, seven solvents-acetone, methanol, ethanol, ethyl acetate, chloroform, water, and hexane-were used to extract the chemical constituents of the fruit of giant fennel (Ferula communis), a species of flowering plant in the carrot family Apiaceae. Specific attributes of these extracts were investigated using in silico simulations and in vitro bioassays. High-performance liquid chromatography equipped with a diode-array detector (HPLC-DAD) identified 15 compounds in giant fennel extract, with p-coumaric acid, 3-hydroxybenzoic acid, sinapic acid, and syringic acid being dominant. Among the solvents tested, ethanol demonstrated superior antioxidant activity and phenolic and flavonoid contents. F. communis extracts showed advanced inhibition of gram-negative pathogens (Escherichia coli and Proteus mirabilis) and variable antifungal activity against tested strains. Molecular docking simulations assessed the antioxidative, antibacterial, and antifungal properties of F. communis, facilitating innovative therapeutic development through predicted compound-protein interactions. In conclusion, the results validate the ethnomedicinal use and potential of F. communis. This highlights its significance in natural product research and ethnopharmacology., (© 2024. The Author(s).)

Cannabis is considered ( Cannabis sativa L.) a sacred herb in many countries and is vastly employed in traditional medicine to remedy numerous diseases, such as diabetes. This research investigates the chemical composition of the aqueous extracts from Cannabis sativa L. seeds. Furthermore, the impact of these extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase enzymes is evaluated, as well as their antihyperglycemic effect. Analysis of the chemical composition of the aqueous extract was conducted using high-performance liquid chromatography with a photodiode array detector (HPLC-DAD). In contrast, the ethanol, hexanic, dichloromethane, and aqueous extract compositions have been established. Additionally, the inhibitory effects of ethanolic, dichloromethane, and aqueous extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase activities were evaluated in vitro and in vivo. The results of HPLC analysis indicate that the most abundant phenolic compound in the aqueous cannabis seed extract is 3-hydroxycinnamic acid, followed by 4-hydroxybenzoic acid and rutin acid. Moreover, administration of ethanolic and aqueous extracts at a dose of 150 mg/Kg significantly suppressed postprandial hyperglycemia compared to the control group; the ethanolic, dichloromethane, and aqueous extracts significantly inhibit pancreatic α-amylase and lipase, and intestinal α-glucosidase in vitro. The pancreatic α-amylase test exhibited an inhibition with IC 50 values of 16.36 ± 1.24 µg/mL, 19.33 ± 1.40 µg/mL, 23.53 ± 1.70 µg/mL, and 17.06 ± 9.91 µg/mL for EAq, EDm, EET, and EHx, respectively. EET has the highest inhibitory capacity for intestinal α-glucosidase activity, with an IC 50 of 32.23 ± 3.26 µg/mL. The extracts inhibit porcine pancreatic lipase activity, demonstrating their potential as lipase inhibitors. Specifically, at a concentration of 1 mg/mL, the highest inhibition rate (77%) was observed for EDm. To confirm these results, the inhibitory effect of these extracts on enzymes was tested in vivo. The oral intake of aqueous extract markedly reduced starch- and sucrose-induced hyperglycemia in healthy rats. Administration of the ethanolic extract at a specific dose of 150 mg/kg significantly reduced postprandial glycemia compared with the control group. It is, therefore, undeniable that cannabis extracts represent a promising option as a potentially effective treatment for type 2 diabetes.

Juncus acutus , acknowledged through its indigenous nomenclature "samar", is part of the Juncaceae taxonomic lineage, bearing considerable import as a botanical reservoir harboring conceivable therapeutic attributes. Its historical precedence in traditional curative methodologies for the alleviation of infections and inflammatory conditions is notable. In the purview of Eastern traditional medicine, Juncus species seeds find application for their remedial efficacy in addressing diarrhea, while the botanical fruits are subjected to infusion processes targeting the attenuation of symptoms associated with cold manifestations. The primary objective of this study was to unravel the phytochemical composition of distinct constituents within J. acutus , specifically leaves (JALE) and roots (JARE), originating from the indigenous expanse of the Nador region in northeastern Morocco. The extraction of plant constituents was executed utilizing an ethanol-based extraction protocol. The subsequent elucidation of chemical constituents embedded within the extracts was accomplished employing analytical techniques based on high-performance liquid chromatography (HPLC). For the purpose of in vitro antioxidant evaluation, a dual approach was adopted, encompassing the radical scavenging technique employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the total antioxidant capacity (TAC) assay. The acquired empirical data showcase substantial radical scavenging efficacy and pronounced relative antioxidant activity. Specifically, the DPPH and TAC methods yielded values of 483.45 ± 4.07 µg/mL and 54.59 ± 2.44 µg of ascorbic acid (AA)/mL, respectively, for the leaf extracts. Correspondingly, the root extracts demonstrated values of 297.03 ± 43.3 µg/mL and 65.615 ± 0.54 µg of AA/mL for the DPPH and TAC methods. In the realm of antimicrobial evaluation, the assessment of effects was undertaken through the agar well diffusion technique. The minimum inhibitory concentration, minimum bactericidal concentration, and minimum fungicidal concentration were determined for each extract. The inhibitory influence of the ethanol extracts was observed across bacterial strains including Staphylococcus aureus , Micrococcus luteus , and Pseudomonas aeruginosa , with the notable exception of Escherichia coli . However, fungal strains such as Candida glabrata and Rhodotorula glutinis exhibited comparatively lower resistance, whereas Aspergillus niger and Penicillium digitatum exhibited heightened resistance, evincing negligible antifungal activity. An anticipatory computational assessment of pharmacokinetic parameters was conducted, complemented by the application of the Pro-tox II web tool to delineate the potential toxicity profile of compounds intrinsic to the studied extracts. The culmination of these endeavors underpins the conceivable prospects of the investigated extracts as promising candidates for oral medicinal applications.

Enzymatic hydrolysis of bovine and human hemoglobin generates a diversity of bioactive peptides, mainly recognized for their antimicrobial properties. However, antimicrobial peptides stand out for their ability to specifically target cancer cells while preserving rapidly proliferating healthy cells. This study focuses on the production of bioactive peptides from hemoglobin and evaluates their anticancer potential using two distinct approaches. The first approach is based on the use of a rapid screening method aimed at blocking host cell protein synthesis to evaluate candidate anticancer peptides, using Lepidium sativum seed germination as an indicator. The results show that: (1) The degree of hydrolysis (DH) significantly influences the production of bioactive peptides. DH levels of 3 to 10% produce a considerably stronger inhibition of radicle growth than DH 0 (the native form of hemoglobin), with an intensity three to four times greater. (2) Certain peptide fractions of bovine hemoglobin have a higher activity than those of human hemoglobin. (3) The structural characteristics of peptides (random coil or alpha helix) play a crucial role in the biological effects observed. (4) The α137-141 peptide, the target of the study, was the most active of the fractions obtained from bovine hemoglobin (IC 50 = 29 ± 1 µg/mL) and human hemoglobin (IC 50 = 48 ± 2 µg/mL), proving to be 10 to 15 times more potent than the other hemoglobin fractions, attributed to its strong antimicrobial potential. The second approach to assessing anticancer activity is based on the preliminary in vitro analysis of hydrolysates and their peptide fractions, with a focus on the eL42 protein. This protein is of major interest due to its overexpression in all cancer cells, making it an attractive potential target for the development of anticancer molecules. With this in mind, astudy was undertaken using a method for labeling formylase (formyl-methionyl-tRNA transformylase (FMTS)) with oxidized tRNA. This approach was chosen because of the similarities in the interaction between formylase and the eL42 protein with oxidized tRNA. The results obtained not only confirmed the previous conclusions but also reinforced the hypothesis that the inhibition of protein synthesis plays a key role in the anticancer mechanism of these peptides. Indeed, the data suggest that samples containing α137-141 peptide (NKT) and total hydrolysates may have modulatory effects on the interaction between FMTS and oxidized tRNA. This observation highlights the possibility that the latter could influence molecular binding mechanisms, potentially resulting in a competitive situation where the ability of substrate tRNA to bind efficiently to ribosomal protein is compromised in their presence. Ultimately, these results suggest the feasibility of obtaining candidate peptides for biological anticancer drugs from both human and bovine hemoglobin sources. These scientific advances show new hope in the fight against cancer, which affects a large number of people around the world.

Background and Objectives : Alzheimer's disease (AD) stands as a pervasive neurodegenerative ailment of global concern, necessitating a relentless pursuit of remedies. This study aims to furnish a comprehensive exposition, delving into the intricate mechanistic actions of medicinal herbs and phytochemicals. Furthermore, we assess the potential of these compounds in inhibiting human acetylcholinesterase through molecular docking, presenting encouraging avenues for AD therapeutics. Materials and Methods : Our approach entailed a systematic exploration of phytochemicals like curcumin, gedunin, quercetin, resveratrol, nobiletin, fisetin, and berberine, targeting their capability as human acetylcholinesterase (AChE) inhibitors, leveraging the PubChem database. Diverse bioinformatics techniques were harnessed to scrutinize molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and adherence to Lipinski's rule of five. Results: Results notably underscored the substantial binding affinities of all ligands with specific amino acid residues within AChE. Remarkably, gedunin exhibited a superior binding affinity (-8.7 kcal/mol) compared to the reference standard. Conclusions: These outcomes accentuate the potential of these seven compounds as viable candidates for oral medication in AD treatment. Notably, both resveratrol and berberine demonstrated the capacity to traverse the blood-brain barrier (BBB), signaling their aptitude for central nervous system targeting. Consequently, these seven molecules are considered orally druggable, potentially surpassing the efficacy of the conventional drug, donepezil, in managing neurodegenerative disorders.

The current study aimed to evaluate the phytochemical composition, quality control, and antioxidant, antibacterial, antifungal, antihyperglycemic activities, and toxicity assessment of Crataegus monogyna Jacq ( C. monogyna ) and Crataegus laciniata Ucria ( C. laciniata) fruits aqueous extracts. The quality control of the plant material revealed that it is free of heavy metals and the acidity and ash parameters comply with international standards. HPLC-DAD analysis revealed the presence of eight phenolic compounds in the C. monogyna extract and nine compounds in the C. laciniata extract, with coumaric acid present only in the C. laciniata extract. According to the findings, both extracts are high in total polyphenols, total flavonoids, and condensed tannins. The results of the antioxidant activity revealed that our extracts have significant effects against 2, 2-diphényl 1-picrylhydrazyle (DPPH), and Ferric Reducing Antioxidant Power (FRAP). The antibacterial test revealed that the two extracts tested were effective against four bacterial strains, including Staphylococcus aureus , Escherichia coli , Enterobacter cloacae , and Shigella dysenteria , but were ineffective against Salmonella typhi , and Acinetobacter baumanii . In addition, extracts from both plants showed remarkable antihyperglycemic activity with no acute toxicity. In conclusion, the extracts studied could be a good source of bioactive molecules with antioxidant, antimicrobial, and anti-diabetic activity for pharmaceutical applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

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., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Pistacia lentiscus L. has traditionally been employed as a diuretic and stimulant in the treatment of hypertension. Our interest centered on analyzing the chemical profile of the plant's leaves and its in vitro, in vivo, and in silico antioxidant, antimicrobial, anticoagulant, and antidiabetic effects in order to valorize this species and prepare new high-value products that can be used in the agro-food and pharmaceutical industries. When this species' essential oil was hydrodistilled and subjected to GC-MS analysis, the results showed that the principal components were germacrene D (17.54%), spathulenol (17.38%), bicyclogermacrene (12.52%), and terpinen-4-ol (9.95%). The extraction of phenolic compounds was carried out by decoction and Soxhlet. The determination of total polyphenols, flavonoids, and tannins of aqueous and organic extracts by spectrophotometric methods demonstrated the richness of this species in phenolic compounds. Chromatographic analysis by HPLC/UV-ESI-MS of the aqueous extract of P. lentiscus revealed the presence of 3,5-di- O -galloyl quinic acid, gallic acid, and 3,4,5-tri- O -galloyl quinic acid specific to this species. The study of antioxidant activity by three methods (DPPH, FRAP, and Total Antioxidant Capacity) revealed that P. lentiscus is a very promising source of natural antioxidants. The antimicrobial activity of the essential oil and aqueous extract (E 0 ) was studied by microdilution on the microplate. The results revealed the effectiveness of the aqueous extract compared to the essential oil against Gram-negative bacteria ( K. pneumoniae , A. baumannii , E. aerogenes , E. cloacae , P. fluorescence , Salmonella sp., Shigella sp., and Y. enterolitica ) and candidoses ( C. krusei and C. albicans ). The measurements of prothrombin time (PT) and activated partial thromboplastin time (aPTT) of the aqueous extract (E 0 ) can significantly prolong these tests from concentrations of 2.875 and 5.750 mg/mL, respectively. The antihyperglycemic effect of the aqueous extract (E 0 ) showed a strong in vitro inhibitory activity of α-amylase and α-glucosidase compared to acarbose. Thus, it significantly inhibited postprandial hyperglycemia in Wistar albino rats. The in-silico study of the major compounds of the essential oil and extract (E 0 ) carried out using PASS, SwissADME, pkCSM, and molecular docking tools confirmed our in vitro and in vivo results. The studied compounds showed a strong ability to be absorbed by the gastrointestinal tract and to passively diffuse through the blood-brain barrier, a similarity to drugs, and water solubility. Molecular docking experiments deduced the probable mode of action of the identified compounds on their respective target proteins, such as NADPH oxidase, thrombin, α-amylase, and α-glucosidase. Furthermore, given the demonstrated antioxidant, antimicrobial, anticoagulant, and antidiabetic effects, we can affirm the richness of P. lentiscus in bioactive molecules and its use in traditional medicine as a source of preservative agent.

In Morocco, many applications in ethnomedicine on Ajuga iva (L.) have been recognized as able to treat various pathologies such as diabetes, stress, and microbial infections. The objective of this work is to carry out phytochemical, biological, and pharmacological investigations on the extracts of Ajuga iva leaves in order to confirm its therapeutic effects. The phytochemical screening carried out on the different extracts of Ajuga iva showed its richness in primary (lipids and proteins) and secondary metabolites (flavonoids, tannins, reducing compounds, oses, and holoside. The best contents of polyphenols, flavonoids, and tannins evaluated by spectrophotometric methods were found in the hydroethanolic extract (69.850 ± 2.783 mg EAG/g DE, 17.127 ± 0.474 mg EQ/g DE, 5.566 ± 0.000 mg EQC/g DE), respectively. Analysis of the chemical composition of the aqueous extract by LC/UV/MS revealed 32 polyphenolic compounds including ferulic acid (19.06%), quercetin (10.19%), coumaric acid (9.63%), and apigenin-7-(2-O-apiosylglucoside) (6.8%). The antioxidant activity of Ajuga iva extracts was evaluated by three methods (DPPH*, FRAP, CAT). The hydroethanolic extract recorded the strongest reducing power: DPPH* (IC 50 = 59.92 ± 0.7 µg/mL), FRAP (EC 50 = 196.85 ± 1.54 (µg/mL), and CAT (199.21 ± 0.37 mg EAG/gE). A strong correlation between phenolic compounds and antioxidant activities was confirmed by the determination of Pearson's coefficient. The antimicrobial activity of Ajuga iva studied by the microtiter method revealed potent antifungal and antibacterial qualities against Candida parapsilosis and Staphylococcus aureus BLACT. An in vivo oral glucose tolerance test (OGTT) using normal rats revealed that the antihyperglycemic action of the aqueous extract significantly reduced postprandial hyperglycaemia at (30 min, p < 0.01) and area under the curve (AUC glucose), p < 0.01. Similarly, the aqueous extract, tested on pancreatic α-amylase enzyme activity in vitro and in vivo significantly inhibited pancreatic α-amylase activity with IC 50 = 1.52 ± 0.03 mg/mL. In conclusion, the extract from Ajuga iva could be a good source of bioactive molecules, which exhibit potent antioxidant and antimicrobial activity, as well as strong antidiabetic activity, for applications in the pharmaceutical industry.

Ziziphus lotus (L.) Lam. (Rhamnaceae) is a plant species found across the Mediterranean area. This comprehensive overview aims to summarize the botanical description and ethnobotanical uses of Z. lotus and its phytochemical compounds derived with recent updates on its pharmacological and toxicological properties. The data were collected from electronic databases including the Web of Science, PubMed, ScienceDirect, Scopus, SpringerLink, and Google Scholars. It can be seen from the literature that Z. lotus is traditionally used to treat and prevent several diseases including diabetes, digestive problems, urinary tract problems, infectious diseases, cardiovascular disorders, neurological diseases, and dermal problems. The extracts of Z. lotus demonstrated several pharmacological properties in vitro and in vivo such as antidiabetic, anticancer, anti-oxidant, antimicrobials, anti-inflammatory, immunomodulatory, analgesic, anti-proliferative, anti-spasmodic, hepatoprotective, and nephroprotective effects. The phytochemical characterization of Z. lotus extracts revealed the presence of over 181 bioactive compounds including terpenoids, polyphenols, flavonoids, alkaloids, and fatty acids. Toxicity studies on Z. lotus showed that extracts from this plant are safe and free from toxicity. Thus, further research is needed to establish a possible relationship between traditional uses, plant chemistry, and pharmacological properties. Furthermore, Z. lotus is quite promising as a medicinal agent, so further clinical trials should be conducted to prove its efficacy.

In order to valorize the species Crocus sativus from Morocco and to prepare new products with high added value that can be used in the food and pharmaceutical industry, our interest was focused on the phytochemical characterization and the biological and pharmacological properties of the stigmas of this plant. For this purpose, the essential oil of this species, extracted by hydrodistillation and then analyzed by GC-MS, revealed a predominance of phorone (12.90%); (R)-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol (11.65%); isopropyl palmitate (9.68%); dihydro- β -ionone (8.62%); safranal (6.39%); trans - β -ionone (4.81%); 4-keto-isophorone (4.72%); and 1-eicosanol (4.55%) as the major compounds. The extraction of phenolic compounds was performed by decoction and Soxhlet extraction. The results of the determination of flavonoids, total polyphenols, condensed tannins, and hydrolyzable tannins determined by spectrophotometric methods on aqueous and organic extracts have proved the richness of Crocus sativus in phenolic compounds. Chromatographic analysis by HPLC/UV-ESI-MS of Crocus sativus extracts revealed the presence of crocin, picrocrocin, crocetin, and safranal molecules specific to this species. The study of antioxidant activity by three methods (DPPH, FRAP, and total antioxidant capacity) has proved that C. sativus is a potential source of natural antioxidants. Antimicrobial activity of the aqueous extract (E 0 ) was investigated by microdilution on a microplate. The results have revealed the efficacy of the aqueous extract against Acinetobacter baumannii and Shigella sp. with MIC ≤ 600 µg/mL and against Aspergillus niger , Candida kyfer , and Candida parapsilosis with MIC = 2500 µg/mL. Measurements of pro-thrombin time (PT) and activated partial thromboplastin time (aPTT) in citrated plasma obtained from routine healthy blood donors were used to determine the anticoagulant activity of aqueous extract (E 0 ). The anticoagulant activity of the extract (E 0 ) studied showed that this extract can significantly prolong the partial thromboplastin time ( p < 0.001) with a 359 µg/mL concentration. The antihyperglycemic effect of aqueous extract was studied in albino Wistar rats. The aqueous extract (E 0 ) showed strong in vitro inhibitory activity of α-amylase and α-glucosidase compared with acarbose. Thus, it very significantly inhibited postprandial hyperglycemia in albino Wistar rats. According to the demonstrated results, we can affirm the richness of Crocus sativus stigmas in bioactive molecules and its use in traditional medicine.

Salvia lavandulifolia Vahl essential oil is becoming more popular as a cognitive enhancer and treatment for memory loss. It is high in natural antioxidants and has spasmolytic, antiseptic, analgesic, sedative, and anti-inflammatory properties. Its aqueous extract has hypoglycemic activity and is used to treat diabetic hyperglycemia, but few studies have focused on it. The objective of this work is to evaluate the various biological and pharmacological powers of Salvia lavandulifolia Vahl leaf aqueous extract. Quality control of the plant material was first carried out. Followed by a phytochemical study on the aqueous extract of S. lavandulifolia leaves, namely phytochemical screening and determination of total polyphenols, flavonoids, and condensed tannins contents. Then, the biological activities were undertaken, in particular the antioxidant activity (total antioxidant activity and trapping of the DPPH° radical) and the antimicrobial activity. The chemical composition of this extract was also determined by HPLC-MS-ESI. Finally, the inhibitory effect of the α-amylase enzyme as well as the antihyperglycaemic effect was evaluated in vivo in normal rats overloaded with starch or D-glucose. The aqueous extract obtained by use of the decoction of leaves of S. lavandulifolia contains 246.51 ± 1.69 mg EQ of gallic acid/g DE, 23.80 ± 0.12 mg EQ quercetin/g DE, and 2.46 ± 0.08 mg EQ catechin /g DE. Its total antioxidant capacity is around 527.03 ± 5.95 mg EQ of ascorbic acid/g DE. At a concentration of 5.81 ± 0.23 µg/mL, our extract was able to inhibit 50% of DPPH° radicals. Moreover, it showed bactericidal effect against Proteus mirabilis , fungicidal against Aspergillus niger , Candida albicans , Candida tropicalis , and Saccharomyces cerevisiae , and fungistatic against Candida krusei . A marked antihyperglycemic activity (AUC = 54.84 ± 4.88 g/L/h), as well as a significant inhibitory effect of α-amylase in vitro (IC 50 = 0.99 ± 0.00 mg/mL) and in vivo (AUC = 51.94 ± 1.29 g/L/h), is recorded in our extract. Furthermore, its chemical composition reveals the presence of 37.03% rosmarinic acid, 7.84% quercetin rhamnose, 5.57% diosmetin-rutinoside, 5.51% catechin dimer, and 4.57% gallocatechin as major compounds. The antihyperglycemic and α-amylase inhibitory activities, associated with the antioxidant properties of S. lavandulifolia , justify its use in the treatment of diabetes in traditional medicine and highlight its potential introduction into antidiabetic drugs.

The aim of this research is to profile the chemical composition of the essential oil (EO) extracted from the aerial parts of Origanum elongatum ( O. elongatum ) and to evaluate its antioxidant, antibacterial and insecticidal activities on Ceratitis capitata adults. Gas chromatography coupled with mass spectrometry (GC/MS) revealed a total of 27 constituents in EO of O. elongatum , which accounted for 99.08% of its constituents. Carvacrol (57.32%) was a main component, followed by p -cymene (14.70%) and γ -terpinene (9.84%). The antioxidant activity of O. elongatum EO was investigated using DPPH (1,1-diphenyl-2-picrylhydrazyl), FRAP (Ferric reducing antioxidant power), and TCA (the total antioxidant capacity) methods. This EO exhibited a remarkable antiradical and reducing power against DPPH (IC 50 = 2.855 ± 0.018μL/mL), FRAP (EC 0.5 = 0.124 ± 0.013µL/mL) and TCA (IC 50 = 14.099 ± 0.389 mg AAE/g of the EO). The antibacterial tests in vitro, using the disc and dilution methods, were carried out on nine pathogenic bacteria isolated from the hospital patients, such as Enterococcus faecalis , Serratia fonticola , Staphylococcus aureus, Acinétobacter baumannii, Klebsiella oxytoca , Klebsiella pneumoniae sensible , E.coli sensible , E.coli resistante , and Enterobacter aerogenes . The EO demonstrated a considerable antibacterial activity with minimum inhibitory concentrations (MIC) from 2 to 8 µL/mL against all strains except Staphylococcus aureus (MIC = 32 µL/mL). Regarding the insecticidal activity, the fumigation test indicated a high efficacy (100% mortality), and a lethal dose of LD 50   =  17 ± 0.53 μL/L air was found after 24 h of exposureTherefore, O. elongatum EO could be utilized as a natural antioxidant, antibiotic and biopesticides.

The present work was aimed to study the toxicity of the essential oils of three aromatic and medicinal plants on the tomato leaf miner Tuta absoluta and the Medfly Ceratitis capitata as an alternative to conventional pesticides. We carried out a phytochemical and insecticide study of T. zygis L., S. officinalis L. and M. suaveolens Ehrh. essential oils (EOs) through the study of their chemical composition and their toxicity on C. capitata adults and T. absoluta larvae. The extraction of the EOs by hydrodistillation showed yields of 3.87 ± 0.03, 4.09 ± 0.23 and 4.35 ± 0.11 for T. zygis , S. officinalis L. and M. suaveolens Ehrh., respectively. The identification of the chemical composition of the EOs by GC/MS showed that oxygenated monoterpenes constituted the most abundant group for all the extracted EOs. The major compounds were rather diversified depending on plant species. In fact, the S. officinalis L. EO mainly contained trans-thujone (21.80 %), the M. suaveolens Ehrh. EO mainly contained piperitenone oxide (71.19%), and carvacrol (61.60%) was the main component of the T. zygis L. EO. An insecticidal effect was observed for the three studied EOs on C. capitata adults and T. absoluta larvae. The observed LD 50 values were 0.80 µL/mL and 11.04 µL/mL for M. suaveolens and S. officinalis , respectively, on T. absoluta larvae. For C. capitata adults, the obtained LD 50 values were 0.9 µL/mL and 11.78 µL/mL for M. suaveolens and T. zygis , respectively. The presented findings could contribute to the development of biopesticides for plants as a component of integrated pest management strategies in citrus and tomato crops.

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, β-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 (IC 50 of 0.36 ± 0.05 mg/mL) in comparison to ascorbic acid (IC 50 of 0.19 ± 0.02 mg/mL). The β-carotene test determined an IC 50 of 2.91 ± 0.14 mg/mL. The IC 50 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).

Punica granatum is a tree of the Punicaceae family which is widespread all over the world with several types of varieties. Its fruit juice is highly prized, whereas the bark, rich in in phytochemicals such as flavonoids, hydrolysable tannins, phenolic acids, and fatty acids, is regarded an agro-industrial waste. It is utilized in traditional medicine for its medicinal properties in the treatment and prevention of a variety of ailments. This study aims to extract and to separate the phytochemical compounds from the bark of P. granatum , to identify them and to study the inhibitory effect of its extracts against antidiabetic activity. First, we carried out successive hot extractions with solvents (chloroform, acetone, methanol, and water) of increasing polarity by the Soxhlet. Then, using both qualitative and quantitative phytochemical investigation, we were able to identify groups of chemicals that were present in all extracts. We identified the majority of the molecular structures of chemicals found in each extract using HPLC-DAD analysis. The inhibition against both intestinal α-glucosidase and pancreatic α-amylase enzymes by P. granatum extracts was used to evaluate their potential antidiabetic effect in vitro. Our results demonstrated the great potential of the acetone extract. Ellagic acid, (-)-catechin, vanillin and vanillic acid were proposed as the most active compounds by the correlation analysis, and their actions were confirmed through the calculation of their IC 50 and the determination of their inhibition mechanisms by molecular modelling. To summarize, these results showed that P. granatum bark, a natural agro-industrial by-product, may constitute a promising option for antidiabetic therapeutic therapy.

Thymus capitatus and Thymus broussonnetii are two Moroccan endemic medicinal plants used traditionally by the local population. The present study aims to investigate their essential oil chemical composition, antioxidant and antibacterial activities. The chemical composition of the essential oils was determined using the GC-MS analysis, the antioxidant activity assessed using DPPH and FRAP methods while the antimicrobial activity was evaluated against nine bacteria species tested ( Enterococcus faecalis , Serratia fonticola , Acinetobacter baumannii , Klebsiella oxytoca , sensitive Klebsiella pneumoniae , sensitive Escherichia coli , resistant Escherichia coli , resistant Staphylococcus aureus and Enterobacter aerogenes ). The major identified compounds of T. capitatus essential oil where carvacrol (75%) and p -cymene (10.58%) while carvacrol (60.79%), thymol (12.9%), p -cymene (6.21%) and γ -terpinene (4.47%) are the main compounds in T. broussonnetii essential oil. The bioactivity of the essential oils of the two species of thyme was explained by their richness in oxygenated monoterpenes known for their great effectiveness with an IC 50 of 3.48 ± 0.05 and 4.88 ± 0.04 μL/mL and EC 50 of 0.12 ± 0.01 and 0.20 ± 0.02 μL/mL in the DPPH and FRAP assays, respectively, with an important antibacterial activity. These results encourage the use of these plants as a source of natural antioxidants, and antibacterial additives, to protect food from oxidative damage and to eliminate bacteria that are responsible for nosocomial infections.

Artemisia absinthium L. is one of the plants which has been used in folk medicine for many diseases over many centuries. This study aims to analyze the chemical composition of the Artemisia absinthium ethyl acetate and its aqueous extracts and to evaluate their effect on the pancreatic α-amylase enzyme and the intestinal α-glucosidase enzyme. In this study, the total contents of phenolic compounds, flavonoids, and condensed tannins in ethyl acetate and the aqueous extracts of Artemisia absinthium leaves were determined by using spectrophotometric techniques, then the antioxidant capacity of these extracts was examined using three methods, namely, the DPPH (2, 2-diphenyl-1picrylhydrazyl) free radical scavenging method, the iron reduction method FRAP, and the β-carotene bleaching method. The determination of the chemical composition of the extracts was carried out using high-performance liquid chromatography-the photodiode array detector (HPLC-DAD). These extracts were also evaluated for their ability to inhibit the activity of the pancreatic α-amylase enzyme, as well as the intestinal α-glucosidase enzyme, in vitro and in vivo, thus causing the reduction of blood glucose. The results of this study showed that high polyphenol and flavonoid contents were obtained in ethyl acetate extract with values of 60.34 ± 0.43 mg GAE/g and 25.842 ± 0.241 mg QE/g, respectively, compared to the aqueous extract. The results indicated that the aqueous extract had a higher condensed tannin content (3.070 ± 0.022 mg EC/g) than the ethyl acetate extract (0.987 ± 0.078 mg EC/g). Ethyl acetate extract showed good DPPH radical scavenging and iron reduction FRAP activity, with an IC 50 of 0.167 ± 0.004 mg/mL and 0.923 ± 0.0283 mg/mL, respectively. The β-carotene test indicated that the aqueous and ethyl acetate extracts were able to delay the decoloration of β-carotene with an inhibition of 48.7% and 48.3%, respectively, which may mean that the extracts have antioxidant activity. HPLC analysis revealed the presence of naringenin and caffeic acid as major products in AQE and EAE, respectively. Indeed, this study showed that the aqueous and ethyl acetate extracts significantly inhibited the pancreatic α-amylase and intestinal α-glucosidase, in vitro. To confirm this result, the inhibitory effect of these plant extracts on the enzymes has been evaluated in vivo. Oral intake of the aqueous extract significantly attenuated starch- and sucrose-induced hyperglycemia in normal rats, and evidently, in STZ-diabetic rats as well. The ethyl acetate extract had no inhibitory activity against the intestinal α-glucosidase enzyme in vivo. The antioxidant and the enzyme inhibitory effects may be related to the presence of naringenin and caffeic acid or their synergistic effect with the other compounds in the extracts.

Lavender aqueous extracts are widely used in the Moroccan traditional medicine for their antibacterial properties. However, previous research have generally focused on investigating the antibacterial activity of lavender essential oils. The aim of this study is to evaluate the antibacterial activity of the Moroccan Lavandula pedunculata (Mill.) Cav. aqueous extract, alone, as well as in combination with extracts of other plant species known for their antibacterial activity: Salvia rosmarinus Spenn., Salvia lavandulifolia Vahl. and Origanum compactum Benth. We have tested the antibacterial activity of L. pedunculata , S. rosmarinus , S. lavandulifolia and O. compactum aqueous extracts individually and in combination against 34 strains using the agar dilution method. The combination effect was evaluated using the fractional inhibitory concentration (FIC). Polyphenol and tannin contents were determined using Folin-Ciocalteu reagent, and then some phenolic compounds were identified using UHPLC-MS. All the extracts displayed a large spectrum of antibacterial activity, especially against staphylococci, streptococci, Mycobacterium smegmatis and Proteus mirabilis . The minimum inhibitory concentration (MIC) values reached 0.15 ± 0.00 mg/mL for Staphylococcus warneri tested with S. lavandulifolia and 0.20 ± 0.07 mg/mL for Staphylococcus epidermidis tested with L. pedunculata or S. rosmarinus . Association of the L. pedunculata extract with S. rosmarinus , S. lavandulifolia and O. compactum showed synergistic effects (FIC ≤ 1). Moreover, the association of L. pedunculata with S. lavandulifolia was active against most of the Gram-negative strains resistant to the individual extracts. Determination of polyphenol and tannin contents showed the richness of the studied plants in these compounds. Additionally, chromatographic analysis demonstrated the high presence of rosmarinic acid in all the studied plant extracts. To our knowledge, this is the first study that shows the enhancing effect of the antibacterial activity of L. pedunculata aqueous extract combined with S. rosmarinus , S. lavandulifolia and O. compactum . These results confirm the effectiveness of the plant mixtures commonly used by traditional healers in Morocco and suggest that L. pedunculata might be used as an antibacterial agent either alone or, more efficiently, in combination with S. rosmarinus , S. lavandulifolia and O. compactum .

Essential oils (EOs) are chemical products produced by odoriferous glands from a variety of plants. These essential oils have many health benefits: antiseptic, anti-inflammatory and antimicrobial activities. So due to these medicinal properties, the present study was designed to analyze essential oils of Thymus zygis L. and Thymus willdenowii Boiss. for their chemical composition and biological activities. These two thyme species were collected from the region of Ifrane, Middle Atlas of Morocco. The EO was obtained by hydrodistillation, and the yields were 5.25% for T. zygis and 3.00% for T. willdenowii . The chemical composition of the EOs was analyzed by gas chromatography coupled with mass spectrometry (GC-MS), and the results showed that T. zygis EO is dominated by carvacrol (52.5%), o- cymene (23.14%), and thymol (9.68%), while the EO of T. willdenowii contains germacrene D (16.51%), carvacrol (16.19%), and geranyl acetate (8.35%) as major compounds. The antioxidant activity assessed by Diphenylpicrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays revealed that both EOs have excellent antioxidant activities; by DPPH it resulted in IC 50 = 6.13 ± 0.11 for T. zygis and 6.78 ± 0.3 µg/mL for T. willdenowii , while the one by FRAP yielded EC 50 = 2.46 ± 0.01 ( T. zygis ) and 5.17 ± 0.2 ( T. willdenowii ) µg/mL. The antimicrobial activity of the two essential oils was evaluated against six bacterial strains and five fungal strains by the disk diffusion method to determine the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC). The EOs revealed variable antimicrobial activities against the different tested microbial strains and showed strong antimicrobial activities, even against strains known as multi-resistant to antibiotics ( Acinetobacter baumannii ) at low concentrations (2 µL/mL). T. zygis EO showed the most powerful activity against all the studied bacteria, while that of T. willdenowii recorded moderate activity when tested against Shigella dysenteriae and Salmonella Typhi. With inhibition diameters that vary between 75 mm and 84 mm for concentrations of 2 µL/mL up to 12 µL/mL, S. aureus was shown to be the most sensitive to T. zygis EO. For the antifungal activity test, T. zygis EO showed the best inhibition diameters compared to T. willdenowii EO. These results showed that T. zygis EO has more powerful antioxidant and antimicrobial activities than T. willdenowii EO, therefore, we deduce that thyme EOs are excellent antioxidants, they have strong antimicrobial properties, and may in the future represent new sources of natural antiseptics that can be used in pharmaceutical and food industry.

Dysphania ambrosioides (L.) Mosyakin and Clemants is an annual or ephemeral perennial herb used traditionally in the Mediterranean region in folk medicine to treat various illnesses, including those related to the digestive system. This study aims to assess the antispasmodic, myorelaxant, and antioxidant effects of D. ambrosioides flower hydroethanolic extract and its chloroform and ethyl acetate fractions in a comparative study to evaluate the result of the extraction type on the potential activity of the extract. Both rat and rabbit jejunum were used to evaluate the antispasmodic and myorelaxant effect, while the antioxidant effect was evaluated using DPPH, a ferric reducing power assay, and a beta-carotene bleaching test. LC/MS-MS analysis was carried out to reveal the composition of the different types of extract. Following the results, the hydroethanolic extract showed a significant myorelaxant effect (IC 50 = 0.39 ± 0.01 mg/mL). Moreover, it was shown that the hydroethanolic extract demonstrated the best antispasmodic activity (IC 50 = 0.51 ± 0.05 mg/mL), followed by the ethyl acetate (IC 50 = 4.05 ± 0.32 mg/mL) and chloroform (IC 50 = 4.34 ± 0.45 mg/mL) fractions. The antioxidant tests showed that the hydroethanolic extract demonstrated high antioxidant activity, followed by the ethyl acetate and chloroform fractions. The LC/MS-MS analysis indicates that the plant extract was rich in flavonoids, to which the extract activity has been attributed. This study supports the traditional use of this plant to treat digestive problems, especially those with spasms.

Lavandula pedunculata (Mill.) Cav. (LP) is one of lavender species traditionally used in Morocco to prevent or cure diabetes, alone or in the form of polyherbal preparations (PHP). Therefore, the primary objective of this study was to test the antihyperglycemic effect of the aqueous extract of LP, alone and in combination with Punica granatum L. (PG) and Trigonella foenum-graecum L. (FGK). The secondary objective was to explore some mechanisms of action on the digestive functions. The antihyperglycemic effect of the aqueous extract of LP, alone and in combination with PG and FGK, was studied in vivo using an oral glucose tolerance test (OGTT). In addition, LP extract was tested on the activities of some digestive enzymes (pancreatic α-amylase and intestinal α-glucosidase) in vitro and on the intestinal absorption of glucose ex vivo using a short-circuit current (I sc ) technique. Acute and chronic oral administration of LP aqueous extract reduced the peak of the glucose concentration (30 min, p < 0.01) and the area under the curve (AUC, p < 0.01). The effect of LP + PG was at the same amplitude to that of the positive control Metformin (MET). LP aqueous extract inhibited the pancreatic α-amylase with an IC 50 almost identical to acarbose (0.44 ± 0.05 mg/mL and 0.36 ± 0.02 mg/mL, respectively), as well as the intestinal α-glucosidase, (IC 50 = 131 ± 20 µg/mL) and the intestinal glucose absorption (IC 50 = 81.28 ± 4.01 µg/mL) in concentration-dependent manners. LP aqueous extract exhibited potent actions on hyperglycemia, with an inhibition on digestive enzymes and glucose absorption. In addition, the combination with PG and FGK enhanced oral glucose tolerance in rats. These findings back up the traditional use of LP in type 2 diabetes treatment and the effectiveness of the alternative and combinative poly-phytotherapy (ACPP).

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.

Citrus fruits and juices have been studied extensively for their potential involvement in the prevention of various diseases. Flavanones, the characteristic polyphenols of citrus species, are the primarily compounds responsible for these studied health benefits. Using in silico and in vitro methods, we are exploring the possible antidiabetic action of narirutin, a flavanone family member. The goal of the in silico research was to anticipate how narirutin would interact with eight distinct receptors implicated in diabetes control and complications, namely, dipeptidyl-peptidase 4 (DPP4), protein tyrosine phosphatase 1B (PTP1B), free fatty acid receptor 1 (FFAR1), aldose reductase (AldR), glycogen phosphorylase (GP), alpha-amylase (AAM), peroxisome proliferator-activated receptor gamma (PPAR-γ), alpha-glucosidase (AGL), while the in vitro study looked into narirutin's possible inhibitory impact on alpha-amylase and alpha-glucosidase. The results indicate that the studied citrus flavanone interacted remarkably with most of the receptors and had an excellent inhibitory activity during the in vitro tests suggesting its potent role among the different constituent of the citrus compounds in the management of diabetes and also its complications.

Due to the high volume of peel produced, Citrus by-product processing could be a significant source of phenolic compounds, in addition to essential oil. Citrus fruit residues, which are usually dumped as waste in the environment, could be used as a source of nutraceuticals. Citrus aurantium (L), also known as sour or bitter orange, is a member of the Rutaceae family and is the result of interspecific hybridization between Citrus reticulata and Citrus maxima . The purpose of this study is to chemically and biologically evaluate the peel of C. aurantium , which is considered a solid waste destined for abandonment. To achieve more complete extraction of the phytochemicals, we used a sequential extraction process with Soxhlet using the increasing polarity of solvents (i.e., cyclohexane, chloroform, ethyl acetate, acetone, and ethanol-water mixture). Essential oil (EO) from the Citrus peel, which was present at 1.12%, was also prepared by hydrodistillation for comparison. Various phytochemical assays were used to determine the qualitative chemical composition, which was subsequently characterized using GC-MS and HPLC-DAD. The inhibitory effects of C. aurantium peel extract on two enzymes, intestinal α-glucosidase and pancreatic α-amylase, were measured in vitro to determine their potential hypoglycemic and antidiabetic actions. Each extract had a significantly different phytochemical composition. According to GC-MS analyses, which allow the identification of 19 compounds, d-limonene is the most abundant compound in both EO and cyclohexane extract, at 35.17% and 36.15% ( w / w ). This comparison with hydrodistillation shows the value of the sequential process in extracting this valuable terpene in large quantities while also allowing for the subsequent extraction of other bioactive substances. On the contrary, linoleic acid is abundant (54.35% ( w / w )) in ethyl acetate extract (EAE) with a lower amount of d-limonene. HPLC-DAD analysis allows the identification of 11 phytochemicals, with naringenin being the most abundant flavanone, detected in acetone extract (ACE) (23.94% ( w / w )), ethanol-water extract mixture (EWE) (28.71% ( w / w )), and chloroform extract (CFE) (30.20% ( w / w )). Several extracts significantly inhibited α-amylase and/or α-glycosidase in vitro. At a dose of 332 g/mL, ACE, CFE, and EWE inhibited the two enzymes by approximately 98%. There were strong significant correlations between naringenin and α-glucosidase inhibition and between gallic acid and α-amylase inhibition. Molecular docking experiments further verified this. Finally, oral administration of C. aurantium extracts at a dose of 2000 mg/kg did not cause any effect on mice mortality or signs of acute toxicity, indicating that it is non-toxic at these doses. These findings suggest that C. aurantium peels could be a valuable by-product by providing a rich source of non-toxic phytoconstituents, particularly those with potential antidiabetic action that needs to be confirmed in vivo.

Cistus ladanifer L. is a plant widely used in folk medicine to treat various illnesses. This study aims to evaluate the effect of the plant flourishing time harvest on the chemical composition and the antimicrobial effect of its essential oil. Chemical analysis of the essential oil was carried out using gas chromatography-mass spectrometry (GC-MS). The antibacterial and antifungal proprieties were tested against four selected bacteria ( Staphylococcus aureus , Salmonella Typhi , Escherichia coli , and Acinetobacter baumannii ) and nine fungi (Yeasts ( Candida tropicalis , Candida glabrata , Candida dubliniensis , Candida sp., Rhodotorula rubra , Cryptococcus neoformans ) and molds ( Penicillium sp. (P), Fusarium sp. (F), Aspergillus niger ( A. niger )), respectively. The essential oil of C. ladanifer demonstrated a powerful antibacterial activity with an inhibition zone of 55 ± 0.22 mm for Staphylococcus aureus, 42 ± 0.11 mm for Escherichia coli, 35 ± 0.27 mm for Acinetobacter baumannii (Full resistant to antibiotics) and 30 ± 0.25 mm for Salmonella Typhi. It also inhibited all tested bacteria at 10 µL/mL. For the antifungal activity test, C. tropicalis and C. neoformans appeared to be the most sensitive strains to the essential oil with an inhibition zone of 13 mm, followed by R. rubra and Penicillium sp. (12 mm), then C. dubliniensis and C. glabrata (11 mm). The chemical analysis of the essential oil by GC-MS revealed that the major components of the essential oil were viridiflorol (17.64%), pinocarveol (11.02%), bornylacetate (9.38%), and ledol (8.85%). C. ladanifer exhibited a remarkable antimicrobial activity that could be more exploited to develop targeted natural remedies against specific diseases.

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.

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., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Mohamed Bouhrim et al.)

Zizyphus lotus L. (Desf.) ( Z. lotus ) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (♂/♀ = 1). The control group was treated orally with distilled water (10 mL/kg); the GM treated group received distilled water (10 mL/kg) and an intraperitoneal injection of GM (80 mg/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use.

Nigella sativa L. ( Ranunculaceae ), commonly referred to as black seeds or black cumin, is used in popular medicine (herbal) all over the world for the treatment and prevention of several diseases, including diabetes. This study aims to investigate the inhibitory effect of N. sativa extracts and fractions against the activities of intestinal α-glucosidase and pancreatic α-amylase in vitro, and to explain the inhibitory effect of these fractions against these enzymes by identifying their active compounds responsible for this effect and determine their modes of inhibition. To do so, N. sativa hexane and acetone extracts were prepared and analyzed by GC-MS and HPLC-DAD, respectively. The hexane extract was further fractioned into eight different fractions, while the acetone extract generated eleven fractions. The extracts as well as the resulting fractions were characterized and evaluated for their potential in vitro antidiabetic activity using intestinal α-glucosidase and pancreatic α-amylase inhibitory assays in vitro. Hexane extract and fractions were less active than acetone extract and fractions. In the case of intestinal α-glucosidase activity, the acetone fraction SA3 had a high inhibitory effect on intestinal α-glucosidase activity with 72.26 ± 1.42%, comparable to the effect of acarbose (70.90 ± 1.12%). For the pancreatic α-amylase enzymatic inhibitory assay, the acetone fractions showed an inhibitory capacity close to that for acarbose. In particular, the SA2 fraction had an inhibitory effect of 67.70 ± 0.58% and was rich in apigenin and gallic acid. From these fractions, apigenin, (-)-catechin, and gallic acid were further characterized for their inhibitory actions. IC 50 and inhibition mode were determined by analyzing enzyme kinetic parameters and by molecular modeling. Interestingly, (-)-catechin showed a possible synergistic effect with acarbose toward α-glucosidase enzyme inhibition, whereas apigenin showed an additive effect with acarbose toward α-amylase enzymatic inhibition. Furthermore, we studied the toxicity of N. sativa hexane and acetone extracts as well as that of acetone fractions. The result of acute toxicity evaluation demonstrated that N. sativa extracts were nontoxic up to a concentration of 10 g/kg, except for fraction SA3. Taken together, these results indicate that N. sativa extracts and/or derived compounds could constitute promising nutraceuticals for the prevention and treatment of type 2 diabetes mellitus.

Leukemia is a group of hematological neoplastic disorders linked to high mortality rates worldwide, but increasing resistance has led to the therapeutic failure of conventional chemotherapy. This study aimed to evaluate in vitro the antileukemic activity and potential mechanism of action of a polyphenolic extract obtained from the seeds of Coriandrum sativum L. (CSP). A methylthiazoletetrazolium assay was performed to assess the CSP cytotoxicity on chronic (K562) and acute (HL60) myeloid leukemia cell lines and on normal Vero cell line. CSP toxicity was also evaluated in vivo using the OECD 423 acute toxicity model on Swiss albino mice. The results demonstrated a remarkable antitumoral activity against K562 and HL60 cell lines (IC 50 = 16.86 µM and 11.75 µM, respectively) although no cytotoxicity was observed for the Vero cells or mice. A silico study was performed on the following receptors that are highly implicated in the development of leukemia: ABL kinase, ABL1 , BCL2 , and FLT3 . The molecular docking demonstrated a high affinity interaction between the principal CSP components and the receptors. Our findings demonstrated that CSP extract has remarkable antileukemic activity, which is mainly mediated by the flavonoids, catechins, and rutin, all of which showed the highest binding affinity for the targeted receptors. This study revealed a promising active compound alternative research-oriented biopharmacists to explore.

Mental disorders are psychological symptoms that impact multiple areas of an individual's life. Depression and anxiety are chronic illnesses described as the most prevalent stress-related mood disorders that cause injury and early death. In Morocco, Anise " Pimpinella anisum L." is one of the most traditionally used condiment plants, which has long been used to cure various illnesses and in phytotherapy. The present study was designed to investigate the antidepressant, anxiolytic, and memory impact of the total extract of Pimpinella anisum (PATE) at the doses of 100 and 200 mg/kg, using the Forced Swimming Test (FST), Tail Suspension Test (TST), Open Field Test (OFT), and Light-Dark Box Test (LDBT) as an experimental paradigm of anxiety and depression, and Novel Object Recognition Test (NORT) and the Morris Water Maze Test (MWMT) as memory tests on Swiss albino mice. The tests were carried out on the 1st, 7th, 14th, and the 21st days of the study, and the extract groups were compared with normal controls and positive controls (receiving bromazepam and paroxetine at the doses of 1 mg/kg and 11.5 mg/kg for anxiety and depression, respectively). The daily oral gavage of the mice by the PATE induced a significant anxiolytic and antidepressant-like effect by shortening immobility time and decreasing downtime in the different tests. PATE at both doses was shown to have no impact on memory following the NORT and MWM tests. Different compounds, such as gallic acid, catechin, chlorogenic acid, caffeic acid, oleuropein, p -coumaric acid, trans-4-hydroxy-3-methoxycinnamic acid, myricetin, and quercetin, were identified during the phytochemical analysis carried out using HPLC analysis. This research supports and promotes the extract's traditional use, suggesting its use as a phytomedicine against depression and anxiety, and calls for further research to clarify its mode of action.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Herbal medicine and its therapeutic applications are widely practiced in northeastern Morocco, and people are knowledgeable about it. Nonetheless, there is a significant knowledge gap regarding their safety. In this study, we reveal the toxic and potential toxic species used as medicines by people in northeastern Morocco in order to compile and document indigenous knowledge of those herbs. Structured and semi-structured interviews were used to collect data, and simple random sampling was used as a sampling technique. Based on this information, species were collected, identified, and herbarium sheets were created. The collected data were analyzed using two quantitative indices: informant consensus factor (ICF) and fidelity level (Fl), as the degree of these indices give an insight into the level of toxicity of a given plant. The results revealed the knowledge of 55 species belonging to 36 families. The most represented families were Apiaceae, Asteraceae, Solanaceae, and Fabaceae. Furthermore, the majority of the species cited were herbs (67%), and the most common toxic parts were seeds, followed by leaves and roots. According to the informant consensus factor, death (0.81%) had the highest agreement, followed by the urological (0.76%) and skin (0.75%) categories. The most significant plants in terms of fidelity level were Solanum sodomaeum L. and Nerium oleander L. for death, Arisarum vulgare O. Targ. Tozz., Mentha spicata L., and Morus alba L. for the digestive category, Petroselinum crispum (Mill.) Fuss. and Citrus x aurantium L. for cardiovascular category, Urtica dioica L. for skin category, Datura stramonium L, and Ephedra altissima Desf. for neurological category, and finally Crocus sativus L. for general and unspecified category. This work highlights a valuable traditional knowledge of poisonous and potential poisonous plants in northeastern Morocco. Further phytochemical and toxicological research is needed to determine the safety of these prized herbs.

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.

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.

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 (IC 50 = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC 50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC 50 = 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.

Background and Aim: Anacyclus pyrethrum (L.) has been used in traditional North African and Indian medicine for the treatment of several diseases such as cancer, rheumatism, epilepsy, diabetes, and Alzheimer's disease. Despite its medical benefits, few studies have examined its toxicity. The present study evaluated the acute toxicity of hydroethanolic extracts of different parts (roots, seeds, leaves, and capitula) of two varieties of A. pyrethrum (L.), namely, A. pyrethrum var. pyrethrum (L) and A. pyrethrum var. depressus (Ball) Maire, in mice., Materials and Methods: Acute toxicity was evaluated after the oral administration of different extracts at doses of 300, 500, and 2000 mg/kg. Mortality, body weight, general behavior, and adverse effects were observed daily for 14 days. At the end of the experiment, mice were sacrificed, and biochemical parameters and histopathology of the liver, kidneys, and spleen were analyzed., Results: The extracts of different parts of both plants induced no signs of toxicity or mortality during the observation period, excluding capitulum and seed extracts, which induced slight sedation at a dose of 2000 mg/kg. The LD 50 of the extracts was estimated to exceed 2000 mg/kg. The administration of A. pyrethrum var. pyrethrum roots at a dose of 300 mg/kg resulted in significantly increased AST levels. However, the A. pyrethrum var. depressus root extract induced significant increases in the levels of both transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). The remaining extracts of both plants at a dose of 500 mg/kg significantly increased AST levels. Moreover, all plant extracts excluding the A. pyrethrum var. pyrethrum capitulum extract at 2000 mg/kg provoked significant increases in AST levels, and A. pyrethrum var. depressus roots provoked a significant increase of ALT levels. Meanwhile, mice treated with high doses of extracts (2000 mg/kg) displayed histopathological changes in the liver, kidneys, and spleen characterized by hepatic distress, inflammatory infiltration, focal tubular necrosis, vascular congestion, and lymphoid hyperplasia., Conclusion: The results of the present study indicate that the hydroethanolic extracts of different parts of two varieties of A. pyrethrum (L.) were not toxic in mice at low concentrations, whereas some toxic effects were detected in mice treated at 2000 mg/kg., (Copyright: © Jawhari, et al.)

The present study aims to evaluate the hepatoprotective activity of stem aqueous extract of Caralluma europaea (AECe) on carbon tetrachloride- (CCl 4 -) 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. CCl 4 was injected (1 ml/kg, i.p .) two times, on the 7 th and 14 th 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 CCl 4 conferred favorable hepatoprotective effect in rats. The treatment with AECe (250 mg/kg) exhibits a significant hepatoprotective effect by ameliorating CCl 4 -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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Hayat Ouassou et al.)

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., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Nour Elhouda Daoudi et al.)

Materials and Methods: Acute toxicity test was performed on Swiss albino mice at a single oral dose of 1-10 g/kg for 14 consecutive days. General behavioral adverse effects, mortality, and latency of mortality were determined. In the subacute study, the Haloxylon scoparium Pomel extract was administered orally at doses of 500, 1000, and 2000 mg/kg daily for 30 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined at the end of the experiment. Sections of livers and kidneys were removed for histological studies., Results: Acute toxicity study showed that the oral LD 50 value of Haloxylon scoparium Pomel extract was 5000 mg/kg. The subacute toxicity study of Haloxylon scoparium Pomel extract at doses 500, 1000, and 2000 mg/kg did not produce any observable symptoms of toxicity and no significant variation in body weight, organ weights, food, and water consumption or mortality in all treated rats. However, the administration of the Haloxylon scoparium Pomel extract to rats at 500 mg/kg and 1000 mg/kg showed a significant decrease in platelets. Moreover, only at the highest dose (2000 mg/kg), the extract caused a significant increase in red blood cells and hemoglobin. Our results showed that subacute treatments with Haloxylon scoparium Pomel extract at doses of 1000 mg/kg and 2000 mg/kg significantly elevated alkaline phosphatase and triglycerides. Histological studies showed that the subacute treatments of rats with Haloxylon scoparium Pomel extracts, at the doses 1000 and 2000 mg/kg, induced some histopathological changes in the livers but a slight changing in kidneys., Conclusion: Our results indicated low acute toxicity of the aqueous extract of Haloxylon scoparium Pomel. Furthermore, daily oral administration of Haloxylon scoparium Pomel extract caused some damages to the livers of rats treated with high doses, expressed by an increase in some enzyme activities such as ALP. Regarding the renal function, we did not find remarkable toxicity in the subacute treatment with Haloxylon scoparium Pomel extracts at doses 1000 and 2000 mg/kg. However, further toxicity assessments should be done to ascertain the safety or the toxicity of this valuable plant species " Haloxylon scoparium pomel" in subchronic treatments., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Loubna Kharchoufa et al.)