Pharmacological activities of chemically characterized essential oils from Haplophyllum tuberculatum (Forssk.)

The present work aimed at characterizing the phytochemical composition of Haplophyllum tuberculatum essential oil (HTEO), assessing its antifungal activity against various fungal strains, evaluating its insecticidal and repulsive properties against Callosobruchus maculatus, and determine its antioxidant capacity. To this end, Gas chromatography-mass spectrometry analysis detected 34 compounds in HTEO, with β-Caryophyllene being the major constituent (36.94%). HTEO demonstrated predominantly modest antifungal effects, however, it sustains notable activity, particularly against Aspergillus flavus, with an inhibition rate of 76.50% ± 0.60%. Minimum inhibitory concentrations ranged from 20.53 ± 5.08 to 76.26 ± 5.08 mg/mL, effectively inhibiting fungal growth. Furthermore, the antifungal, and antioxidant activities of HTEO were evaluated in silico against the proteins Aspergillus flavus FAD glucose dehydrogenase, and beta-1,4-endoglucanase from Aspergillus niger, NAD(P)H Oxidase. Moreover, HTEO displayed strong insecticidal activity against C. maculatus, with contact and inhalation tests yielding LC50 values of 30.66 and 40.28 μL/100g, respectively, after 24 h of exposure. A dose of 5 μL/100g significantly reduced oviposition (48.85%) and inhibited emergence (45.15%) compared to the control group. Additionally, HTEO exhibited a high total antioxidant capacity of 758.34 mg AAE/g EO, highlighting its antioxidant potential. Insilico results showed that the antifungal activity of HTEO is mostly attributed to γ-Cadinene and p-Cymen-7-ol, while antioxidant is attributed to α-Terpinyl isobutyrate displayed. Overall, HTEO offers a sustainable and environmentally friendly alternative to synthetic products used to manage diseases

Origanum majorana L. polyphenols: in vivo antiepileptic effect, in silico evaluation of their bioavailability, and interaction with the NMDA receptor

Introduction: Epilepsy is a chronic brain disease characterized by repeated seizures and caused by excessive glutamate receptor activation. Many plants are traditionally used in the treatment of this disease. This study aimed to evaluate the bioavailability of a polyphenolic extract obtained from Origanum majorana L. (OMP) leaves, as well as its antiepileptic activity and its potential mechanism of action.Methods: We have developed and validated a simple, rapid, and accurate stability-indicating reversed-phase liquid chromatographic method for the simultaneous determination of caffeine and quercetin in rat plasma. The OMP antiepileptic effect was evaluated with pilocarpine-induced seizures, and a docking method was used to determine the possible interaction between caffeic acid and quercetin with the N-methyl-D-aspartate (NMDA) receptor.Results and Discussion: Both compounds tested showed low bioavailability in unchanged form. However, the tested extract showed an anticonvulsant effect due to the considerably delayed onset of seizures in the pilocarpine model at a dose of 100 mg/kg. The molecular docking proved a high-affinity interaction between the caffeic acid and quercetin with the NMDA receptor. Taken together, OLP polyphenols demonstrated good antiepileptic activity, probably due to the interaction of quercetin, caffeic acid, or their metabolites with the NMDA receptor

Lipids Fraction from Caralluma europaea (Guss.): MicroTOF and HPLC Analyses and Exploration of Its Antioxidant, Cytotoxic, Anti-Inflammatory, and Wound Healing Effects

Caralluma europaea is a medicinal plant used in Morocco to cure a variety of illnesses. This study was conducted to determine the chemical composition, the antioxidant, antiproliferative, anti-inflammatory, and wound healing activities of C. europaea lipids. The chemical composition of C. europaea was analyzed using time-of-flight mass spectrometry and high-performance liquid chromatography. The antioxidant potential was determined using the 2,2-di-phenyl-1-picryl hydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) tests. The antiproliferative effect was evaluated by MTT assay against HL60, K562, Huh-7 cancer cells, and normal Vero cells. The anti-inflammatory potential was conducted against carrageenan-induced paw edema. The wound healing effect was evaluated against skin burns for 21 days. The identified phytochemical compounds were docked for their effect on nicotinamide adenine dinucleotide phosphate oxidase, caspase-3, lipoxygenase, glycogen synthase kinase-3-β, and protein casein kinase-1. The results showed the presence of some lipids, such as linoleic acid and vitamin D3. The DPPH (IC50 = 0.018 mg/mL) and FRAP (EC50 = 0.084 mg/mL) of C. europaea lipids showed an important antioxidant effect. For the anti-inflammatory test, an inhibition of 83.50% was recorded after 6 h of treatment. Our extract showed the greatest wound retraction on the 21st day (98.20%). C. europaea lipids showed a remarkable antitumoral effect against the K562 cell line (IC50 = 37.30 µg/mL), with no effect on Vero cells (IC50 > 100 µg/mL). Lignoceric acid was the most active molecule against caspase-3 (−6.453 kcal/mol). The findings indicate the growing evidence of C. europaea as a potential treatment for several diseases

Pharmacovigilance of the Covid19 therapeutic protocol: Experience of the Hassan II University Hospital of Fez, Morocco and analysis of national and international data

Faced with the pandemic related to the dissemination of the new Coronavirus and the health emergency, Morocco decided to treat patients with Covid-19 with Hydroxychloroquine (HCQ) or Chloroquine (CQ), associated with Azithromycin (AZM) according to a standardized therapeutic scheme, an off-label indication that required pharmacovigilance monitoring to ensure the safety of treated patients. Objective. To present the experience of the Hassan II University Hospital of Fez concerning the management of adverse events of the Covid19 therapeutic protocol. A notification form was made available to the nursing staff to be filled in for any adverse reaction (ADR) observed after the treatment was taken. A daily collection and in-depth analysis was performed. We present the results of the analysis of the data collected in our training between April 21 and August 22, 2020, discussing them with data from national and international databases. 102 ADR cases were collected out of 915 patients hospitalized at the UHC for Covid19 during this period with a prevalence of 11%. 23 patients had underlying defects. The incriminating protocol contained CQ in 55.8% and HCQ in 44.2%. The mean age of the patients was 40.83±17.1 years (18 to 86 years) with a M/F sex ratio of 0.92. The mean time to onset was 3 days (range 1-6 days). The most noted ADRs were digestive, cardiac and neurological. 14 cases were severe (one QT prolongation), 6 of which required transfer to an intensive care unit. The course of action adopted was the restoration of corrective treatment with 12 cases of treatment discontinuation and 8 cases of switching to 2nd line treatment

Study of the Phytochemical Composition, Antioxidant Properties, and In Vitro Anti-Diabetic Efficacy of Gracilaria bursa-pastoris Extracts

International audienc

Chemical Characterization, Antioxidant, Insecticidal and Anti-Cholinesterase Activity of Essential Oils Extracted from <i>Cinnamomum verum</i> L.

This study is aimed at evaluating the potential of the essential oil of Cinnamomum verum (EOCV) as an antioxidant, as an insecticide against Callosobruchus maculatus and for its anti-acetylcholinesterase activity. To this end, EOCV was extracted via hydrodistillation from this plant, and the identification of the phytochemicals was performed using gas chromatography–mass spectrometry (GC–MS). The antioxidant power was determined via in vitro tests, the insecticidal ability was tested via exposing C. maculatus to EOCV, and molecular docking was used to evaluate the anti-cholinesterase ability. The results of these GC–MS analyses show that the main composition of EOCV comprises Cinnamaldehyde dimethyl acetal (64.50%), cinnamicaldehyde (35.04%) and α-Copaene (0.11%). The insecticidal potential of the studied OEs, determined by using the inhalation test, and expressed as the concentration of EOs required for the death of 50% of the insects (LC50) and that required the death of 95% of adults (LC95) after 96 h of exposure, was 3.99 ± 0.40 and 14.91 ± 0.10 μL/L of air, respectively. In the contact test, 96 h of exposure gave an LC50 and LC95 of 3.17 ± 0.28 and 8.09 ± 0.05 μL/L of air, respectively. A comparison of the antioxidant activity of EOCV to that of ascorbic acid via DPPH free radical scavenging ability and Ferric Reducing Antioxidant Power (FRAP) revealed the IC50 and EC50 values of EOCV to be much higher than that obtained for ascorbic acid, and the molecular docking simulation revealed Coumarin, Piperonal, Cinnamaldehyde dimethyl and alpha-Copaene as possessing potential inhibitory activities against human acetylcholinesterase. However, further experimental validation is needed to enhance the prospects of this study

Phytochemistry and Biological Activities of Essential Oils from <i>Satureja calamintha</i> Nepeta

Satureja calamintha nepeta (S. calamintha) has a history of successful use in the treatment of bacterial and fungal diseases. The present study was designed to investigate the chemical composition and antioxidant and antimicrobial activities of essential oils extracted from wild S. calamintha (EOSS) and domesticated S. calamintha (EOSD) for comparison purposes. Hydrodistillation was used to extract the essential oils (EOs), while GC/MS was used for chemical analysis. Antioxidant activity was studied using DPPH and FRAP assays. Antifungal activity was performed against Candida albicans, Aspergillus niger, Aspergillus flavus, and Fusarium oxysporum), while antibacterial activity was tested against clinically resistant bacteria, namely Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Proteus mirabilis. By using ab=n in silico approach, the antioxidant and antimicrobial activities of the main compounds of EOSS and EOSD were also investigated. The yields obtained of EOSS and EOSD were 2.80% and 1.95%, respectively, with a dominance of eucalyptol, pulegone and rotundifolone. Concerning the antioxidant power, the IC50 values recorded by the use of the DPPH assay were in the range of 23.03 ± 4.30 and 24.09 ± 4.38 μg/mL for EOSS and EOSD, respectively, while by using the FRAP assay, the EC50 values were in the range of 55.38 ± 2.16 and 60.72 ± 7.71 μg/mL for EOSS and EOSD, respectively. Importantly, both essential oils of EOSS and EOSD exhibited good antibacterial activity against all studied bacteria; notably, the inhibition zone ranged from 14 ± 0.00 to 48.67 ± 1.15 mm and the MICs ranged from 0.37 ± 0.00 to 5.96 ± 0.00 µg/mL. Similarly, the studied EOs showed important antifungal activities compared to all the studied fungi, wherein the inhibition percentage ranged from 47.33 ± 1.15 to 89.18 ± 0.75%, while the MICs ranged from 0.18 ± 0.00 to 2.98 ± 0.00 µg/mL. The molecular docking results showed that piperitenone and pulegone strongly inhibited human acetylcholinesterase, whereas (+)-Isomenthone and piperitenone strongly inhibited S. aureus nucleoside diphosphate kinase, and E. coli beta-ketoacyl-[acyl carrier protein] synthase, respectively. The outcome of this article suggests that EOs of S. calamintha can be developed as alternative agents to manage drug-resistant phenomena and free radical issues

Antioxidant, Anti-Proliferative Activity and Chemical Fingerprinting of Centaurea calcitrapa against Breast Cancer Cells and Molecular Docking of Caspase-3

Centaurea calcitrapa has been intensively utilized in ethnomedicinal practices as a natural therapeutic recipe to cure various ailments. The current study aimed to chemically characterize ethanolic extract of C. calcitrapa (EECC) aerial parts (leaves and shoots) by use of gas chromatography-mass spectrometry analyses (GC-MS) and investigate its antioxidant and in vitro anticancer activities, elucidating the underlying molecular mechanism by use of flow cytometry-based fluorescence-activated cell sorting (FACS) and conducting in silico assessment of binding inhibitory activities of EECC major compounds docked to caspase-3. CG-MS profiling of EECC identified a total of 26 major flavonoids and polyphenolic compounds. DPPH and ABTS assays revealed that EECC exhibits potent antioxidant activity comparable to standard reducing agents. Results of the proliferation assay revealed that EECC exhibit potent, dose-dependent cytotoxic activities against triple-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell models, with IC50 values of 1.3 &times; 102 and 8.7 &times; 101 &micro;g/mL, respectively. The observed cytotoxic effect was specific to studied cancer cells since EECC exhibited minimal (~&lt;10%) cytotoxicity against MCF-12, a normal breast cell line. FACS analysis employing annexin V-FITC/propidium iodide double labeling demonstrated that the observed anti-proliferative activity against MCF-7 and MDA-MB-231 was mediated via apoptotic as well as necrotic signaling transduction processes. The increase in fluorescence intensity associated with DCFH oxidation to DCF, as reported by FACS, indicated that apoptosis is caused by generation of ROS. The use of caspase-3-specific fluorogenic substrate revealed a dose-dependent elevation in caspase-3 substrate-cleavage activity, which further supports EECC-mediated apoptosis in MCF-7 cells. The major EECC compounds were examined for their inhibitory activity against caspase-3 receptor (1HD2) using molecular docking. Three compounds exhibited the highest glide score energy of &minus;5.156, &minus;4.691 and &minus;4.551 kcal/mol, respectively. Phenol, 2,6-dimethoxy established strong binding in caspase-3 receptor of hydrogenic type, with residue ARG 207 and of PI-PI stacking type with residue HIS 121. By contract, hexadecenoic acid showed 3 H-bond with the following residues: ASN 615, ASN 616a and THR 646. Taken together, the current findings reveal that EECC exhibits significant and specific cytotoxicity against breast cancer cells mediated by the generation of ROS and culminating into necrosis and apoptosis. Further investigations of the phytoconstituents-rich C. calcitrapa are therefore warranted against breast as well as other human cancer cell models

Phenolic Composition, Wound Healing, Antinociceptive, and Anticancer Effects of <i>Caralluma europaea</i> Extracts

Caralluma europaea (Guss.) is an important medicinal plant widely used in Morocco for various traditional purposes. Our work aimed to evaluate the phenolic composition, wound healing, antinociceptive, and anticancer activities of C. europaea extracts. Moreover, this study assessed the beneficial effect of C. europaea phytocompounds on the TRADD, cyclooxegenase-2, Wnt/β-catenin, and tyrosine kinase signaling pathways. The wound healing effect of C. europaea formulations against skin burn was evaluated for 21 days. The cytotoxic effect of the C. europaea extracts was evaluated against human leukemic (K562 and HL60) and liver cancer cell lines (Huh-7) using the MTT test. All the phytoconstituents identified by UHPLC in the polyphenols were docked for their inhibitory power on protein casein kinase-1, glycogen synthase kinase-3-β, cyclooxegenase-2, tyrosine kinase, and TRADD. Luteolin and kaempferol are the main compounds identified in C. europaea polyphenols. The group treated with polyphenols showed the greatest wound contractions and all tested extracts presented a significant antinociceptive effect. Polyphenols showed a remarkable antitumoral activity against the K562, HL60 and Huh-7 cell lines. Saponins exerted an important cytotoxic effect against the Huh-7 cell line, whereas no cytotoxicity was observed for the hydroethanolic and flavonoids extracts. Hesperetin and trimethoxyflavone presented the highest docking G-score on tyrosine kinase and cyclooxygenase, respectively

The LC-MS/MS Identification and Analgesic and Wound Healing Activities of <i>Lavandula officinalis</i> Chaix: In Vivo and In Silico Approaches

We earlier emphasized in vivo the lavender plant’s (Lavandula officinalis Chaix.) anti-inflammatory and estrogenic activities and described the chemical compositions of its hydro-ethanolic (HE) extract. We used LC-MS/MS and GC-MS analyses to profile the phytochemical composition of the HE extract and to assess the analgesic and wound-healing effects of both the hydro-ethanolic (HE) and polyphenolic (LOP) extracts in vivo and in silico. The analgesic activity was studied using two methods: acetic acid and formalin injections in mice. The wound-healing activity was carried out over 25 days using a burn model in rats. In the in silico study, the polyphenols identified in the plant were docked in the active sites of three enzymes: casein kinase-1, cyclooxygenase-2, and glycogen synthase kinase-3β. The LC-MS/MS identified some phenolic compounds, mainly apigenin, catechin, and myricetin, and the GC-MS analysis revealed the presence of 19 volatile compounds with triazole, D-glucose, hydroxyphenyl, and D-Ribofuranose as the major compounds. The HE and LOP extracts showed significant decreases in abdominal writhes, and the higher licking time of the paw (57.67%) was observed using the LOP extract at 200 mg/kg. Moreover, both extracts showed high healing percentages, i.e., 99.31 and 92.88%, compared to the control groups, respectively. The molecular docking showed that myricetin, amentoflavone, apigenin, and catechin are the most active molecules against the three enzyme receptors. This study sheds light on the potential of L. officinalis Chaix as a source of natural products for pharmaceutical applications for analgesic purposes as well as their utility in promoting burn-healing activity