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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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