Exploring Medicinal Herbs' Therapeutic Potential and Molecular Docking Analysis for Compounds as Potential Inhibitors of Human Acetylcholinesterase in Alzheimer's Disease Treatment.

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.

Quality control, phytochemical profile, and biological activities of Crataegus monogyna Jacq. and Crataegus laciniata Ucria fruits aqueous extracts.

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.

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

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

Ethnobotanical, Phytochemical, Toxicological, and Pharmacological Properties of Ziziphus lotus (L.) Lam.: A Comprehensive Review.

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.

Chemical Composition, Antioxidants, Antibacterial, and Insecticidal Activities of Origanum elongatum (Bonnet) Emberger & Maire Aerial Part Essential Oil from Morocco.

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 (IC50 = 2.855 ± 0.018µL/mL), FRAP (EC0.5 = 0.124 ± 0.013µL/mL) and TCA (IC50 = 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 LD50 = 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.

Crocus sativus L. Stigmas, Tepals, and Leaves Ameliorate Gentamicin-Induced Renal Toxicity: A Biochemical and Histopathological Study.

The most costly spice in the world, Crocus sativus L. (C. sativus), has been used for more than 3,000 years. It has various beneficial applications in a range of fields, including aromas, colorants, and medications, but its usefulness as a food flavoring and coloring ingredient is the highest. Large quantities of by-products from the processing of saffron are typically thrown as unwanted bio-residues. This study's goal was to assess and compare the nephroprotective effects of hydroethanolic extracts of C. sativus stigmas, tepals, and leaves on gentamicin (GM)-induced nephrotoxicity in rats. For that, we used a biochemical and histological investigation to propose new pharmaceutical valorizations. Based on the biochemical and histological analyses, it is concluded that all the studied parts of C sativus showed a renoprotective effect. Markedly, tepals revealed the most significant reduction of relative liver weight (p < 0.05), water intake (p < 0.05), plasma creatinine (p < 0.01), plasma urea (p < 0.01), plasma uric acid (p < 0.05), urinary protein (p < 0.01) and albumin (p < 0.001), and renal malondialdehyde (MDA) (p < 0.001). In addition, C. sativus tepals caused a significant increase in body weight (p < 0.05), urinary creatinine (p < 0.01), creatinine clearance (p < 0.05), and urinary urea (p < 0.05) compared with the gentamicin untreated (GM) group. This is confirmed by the histopathological study which shows that treatment with stigmas, tepals, and leaves preserved kidney morphology at the glomerular and tubular cell level. The studied extracts exhibit good recovery potential for nephrotoxicity induced by gentamicin. In order to create potent dietary supplements or phytomedicines, it would also be very interesting to confirm these actions through clinical research.

Antioxidant Activity, Metal Chelating Ability and DNA Protective Effect of the Hydroethanolic Extracts of Crocus sativus Stigmas, Tepals and Leaves.

The present study investigated the antioxidant activity, metal chelating ability and genoprotective effect of the hydroethanolic extracts of Crocus sativus stigmas (STG), tepals (TPL) and leaves (LV). We evaluated the antioxidant and metal (Fe2+ and Cu2+) chelating activities of the stigmas, tepals and leaves of C. sativus. Similarly, we examined the genotoxic and DNA protective effect of these parts on rat leukocytes by comet assay. The results showed that TPL contains the best polyphenol content (64.66 µg GA eq/mg extract). The highest radical scavenging activity is shown by the TPL (DPPH radical scavenging activity: IC50 = 80.73 µg/mL). The same extracts gave a better ferric reducing power at a dose of 50 µg/mL, and better protective activity against ß-carotene degradation (39.31% of oxidized ß-carotene at a 100 µg/mL dose). In addition, they showed a good chelating ability of Fe2+ (48.7% at a 500 µg/mL dose) and Cu2+ (85.02% at a dose of 500 µg/mL). Thus, the antioxidant activity and metal chelating ability in the C. sativus plant is important, and it varies according to the part and dose used. In addition, pretreatment with STG, TPL and LV significantly (p < 0.001) protected rat leukocytes against the elevation of percent DNA in the tail, tail length and tail moment in streptozotocin- and alloxan-induced DNA damage. These results suggest that C. sativus by-products contain natural antioxidant, metal chelating and DNA protective compounds, which are capable of reducing the risk of cancer and other diseases associated with daily exposure to genotoxic xenobiotics.

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

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

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

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

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

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

In Vivo and In Vitro Antidiabetic and Anti-Inflammatory Properties of Flax (Linum usitatissimum L.) Seed Polyphenols.

Flaxseed is an oilseed (45-50% oil on a dry-weight basis) crop. Its oil has demonstrated multiple health benefits and industrial applications. The goal of this research was to evaluate the antidiabetic and anti-inflammatory potential of the free polyphenol fraction of flax (Linum usitatissimum L.) seeds (PLU), based on their use in traditional medicine. Mice with alloxan-induced diabetes were used to study the antidiabetic activity of PLU in vivo, with an oral administration of 25 and 50 mg/kg over 28 days. Measurements of body weight and fasting blood glucose (FBG) were carried out weekly, and biochemical parameters were evaluated. An oral glucose tolerance test was also performed. Inhibitory activities of PLU on α-amylase and α-glucosidase activities were evaluated in vitro. The anti-inflammatory was evaluated in vivo in Wistar rats using the paw edema induction Test by carrageenan, and in vitro using the hemolysis ratio test. PLU administration to diabetic mice during the study period improved their body weight and FBG levels remarkably. In vitro inhibitory activity of digestive enzymes indicated that they may be involved in the proposed mode of action of PLU extract. Qualitative results of PLU revealed the presence of 18 polyphenols. These findings support daily consumption of flaxseed for people with diabetes, and suggest that polyphenols in flaxseed may serve as dietary supplements or novel phytomedicines to treat diabetes and its complications.

The Nephroprotective Effect of Zizyphus lotus L. (Desf.) Fruits in a Gentamicin-Induced Acute Kidney Injury Model in Rats: A Biochemical and Histopathological Investigation.

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.

Assessment of Antidepressant-like, Anxiolytic Effects and Impact on Memory of Pimpinella anisum L. Total Extract on Swiss Albino Mice.

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.

Potential Toxicity of Medicinal Plants Inventoried in Northeastern Morocco: An Ethnobotanical Approach.

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.

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

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

Acute and Subacute Toxicity Studies of the Aqueous Extract from Haloxylon scoparium Pomel (Hammada scoparia (Pomel)) by Oral Administration in Rodents.

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 LD50 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.

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

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

Protective Effect of Zizyphus lotus L. (Desf.) Fruit against CCl4-Induced Acute Liver Injury in Rat.

In Morocco, "Zizyphus lotus L." is one of the most widely and traditionally used plant species to treat various diseases, including liver disorders. The present study was conducted to evaluate the aqueous extract of Zizyphus lotus L. fruit against carbon tetrachloride- (CCL4-) induced liver damage in Wistar rats. The animals were daily treated with the aqueous extract of Zizyphus lotus L. fruit using two doses separately 200 and 400 mg/kg body weight for 14 days. CCL4 was injected intraperitoneally (1 ml/kg body weight) at two times, 7th and 14th days. At the end of the treatment, rats were sacrificed, and the blood was collected for the assessment of biochemical parameters. Moreover, the body weight as well as liver weight was determined. The injection of CCl4 to the rats induced various alterations such as the increase of relative liver weight, serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, triglycerides, very low-density lipoproteins, total cholesterol (slight increase), creatinine, urea, uric acid, and malondialdehyde. On the contrary, the effects of CCL4 lead to the reduction in serum levels of high-density lipoprotein. However, the daily administration of the aqueous extract of Zizyphus lotus L. fruit to the injected rats with CCL4 restored this abnormal variation in these biochemical parameters to normal values. Based on the results obtained in this study, it seems that the aqueous extract of Zizyphus lotus L. fruit has an hepatoprotective effect against hepatic lesions induced by CCL4 in rats.