Extracellular Vesicles Derived from Opuntia ficus-indica Fruit (OFI-EVs) Speed Up the Normal Wound Healing Processes by Modulating Cellular Responses.

Plant-derived extracellular vesicles (EVs) have been recognized as important mediators of intercellular communication able to transfer active biomolecules across the plant and animal kingdoms. EVs have demonstrated an impressive array of biological activities, displaying preventive and therapeutic potential in mitigating various pathological processes. Indeed, the simplicity of delivering exogenous and endogenous bioactive molecules to mammalian cells with their low cytotoxicity makes EVs suitable agents for new therapeutic strategies for a variety of pathologies. In this study, EVs were isolated from Opuntia ficus-indica fruit (OFI-EVs) and characterized by particle size distribution, concentration, and bioactive molecule composition. OFI-EVs had no obvious toxicity and demonstrated a protective role in the inflammatory process and oxidative stress in vitro model of chronic skin wounds. The results demonstrated that pretreatment with OFI-EVs decreased the activity and gene expression of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α) in the LPS-stimulated human leukemia monocytic cell line (THP-1). Furthermore, OFI-EVs promote the migration of human dermal fibroblasts (HDFs), speeding up the normal wound healing processes. This study sheds light, for the first time, on the role of OFI-EVs in modulating important biological processes such as inflammation and oxidation, thereby identifying EVs as potential candidates for healing chronic cutaneous wounds.

The chemical composition and the preservative, antimicrobial, and antioxidant effects of Thymus broussonetii Boiss. essential oil: an in vitro and in silico approach.

Introduction: The aim of this study was to evaluate the antioxidant, antimicrobial, and preservative efficacy of Thymus broussonetii Boiss. essential oil (EO) in a topically applied formulation using a challenge test. Methods: The essential oil was extracted from the aerial part of T. broussonetii using hydrodistillation, and the obtained EO was further analyzed by gas chromatography/mass spectrometry (GC/MS). The antioxidant effect of the EO was evaluated using three methods: the inhibition of free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), ß-carotene-linoleic acid, and the ferric reducing antioxidant power (FRAP) methods. The antimicrobial activity and the minimum inhibitory concentration (MIC) of this EO were assayed by the disk-diffusion method and the broth microdilution method, respectively. The preservative efficacy of T. broussonetii EO was assayed at 1% and 2% (v/w) in a topical cream formulation using a challenge test against standard-specific microorganisms recommended by the European Pharmacopoeia. Furthermore, the identified phytochemical compounds were docked for their effect on nicotinamide adenine dinucleotide phosphate oxidase, human casein kinase 1 alpha 1 (CSNK1A1), glycogen synthase kinase 3, Staphylococcus aureus nucleoside diphosphate kinase, Escherichia coli beta-ketoacyl-[acyl-carrier protein] synthase, Pseudomonas aeruginosa LasR ligand-binding domain, and sterol 14-alpha demethylase (CYP51) from Candida albicans. The ADME/toxicity was predicted by analyzing the absorption, distribution, metabolism, and excretion parameters. Results and discussion: chemical composition of the EO revealed the presence of thymol (63.09%), p-cymene (11%), and γ-terpinene (8.99%) as the major components. The antioxidant assays revealed that the essential oil exhibited strong antioxidant activity, as indicated by the minimum inhibitory concentration IC50 (IC50 = 210 ± 0.3 µg/mL for the DPPH assay, IC50 = 145 ± 0.1 µg/mL for the ß-carotene assay, and IC50 = 84 ± 0.21 µg/mL for the FRAP assay) when compared to quercetin and butylated hydroxytoluene (BHT) as controls. The investigated essential oil exhibited important antimicrobial activity against all the tested microorganisms, and the MICs of the EO against bacteria and fungi were 0.02%-1%. Moreover, the EO of T. broussonetii evaluated at 2% (v/w) in a cream formulation succeeded in satisfying the A criteria for preservation efficacy against S. aureus, E. coli, and Aspergillus brasiliensis but exhibited less efficacy against P. aeruginosa (1.78 log reduction in the number of CFU/g after 7 days of evaluation) and C. albicans (1.09 log reduction in the number of CFU/g after 14 days of evaluation) when compared to the synthetic preservative phenoxyethanol 1% (v/w). In silico results showed that the antimicrobial activity of T. broussonetii EO is mostly attributed to thymol, terpinen-4-ol, and aromadendrene, while the antioxidant activity is attributed to thymol. These results indicate that the EO of T. broussonetii possesses important antimicrobial and antioxidant properties and can, therefore, be used as a natural preservative ingredient in the cosmetic industry.

In vivo and in silico studies of the effects of oil extracted from Cannabis sativa L. seeds on healing of burned skin wounds in rats.

Introduction: This study investigates the potential effects of cannabis seed oil (CSO) on the wound healing process. The aim was to assess the efficacy of CSO in treating skin wounds using an animal model and to explore its anti-inflammatory properties through in silico analysis. Methods: Eighteen male albino Wistar rats, weighing between 200 and 250 g, were divided into three groups: an untreated negative control group, a group treated with the reference drug silver sulfadiazine (SSD) (0.01 g/mL), and a group treated topically with CSO (0.962 g/mL). The initial wound diameter for all groups was 1 cm. In silico studies were conducted using Maestro 11.5 to evaluate the anti-inflammatory effects of phytoconstituents against cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Results: CSO and SSD treatments led to a significant reduction (p <0.05) in the size of burned skin wounds by day 5, with contraction rates of 53.95% and 45.94%, respectively, compared to the untreated negative control group. By day 15, wounds treated with CSO and SSD had nearly healed, showing contraction rates of 98.8% and 98.15%, respectively. By day 20, the wounds treated with CSO had fully healed (100%), while those treated with SSD had almost completely healed, with a contraction rate of 98.97%. Histological examination revealed granulated tissue, neo-blood vessels, fibroblasts, and collagen fibers in wounds treated with CSO. In silico studies identified arachidic acid, γ-linolenic acid, and linolenic acid as potent inhibitors of COX-1 and COX-2. Serum biochemical parameters indicated no significant changes (p > 0.05) in liver and kidney function in rats treated with CSO, whereas a significant increase (p < 0.01) in ALAT level was observed in rats treated with SSD. Discussion: The findings demonstrate that CSO has a promising effect on wound healing. The CSO treatment resulted in significant wound contraction and histological improvements, with no adverse effects on liver and kidney function.However, the study's limitations, including the small sample size and the need for detailed elucidation of CSO's mechanism of action, suggest that further research is necessary. Future studies should focus on exploring the molecular pathways and signaling processes involved in CSO's pharmacological effects.

Phenolic Composition of Crataegus monogyna Jacq. Extract and Its Anti-Inflammatory, Hepatoprotective, and Antileukemia Effects.

Crataegus monogyna (C. monogyna) is a prominent plant used in Moroccan traditional medicine. This study investigated the phenolic composition and the anti-inflammatory, the hepatoprotective, and the anticancer activities of a hydroethanolic extract of C. monogyna leaves and stems. Ultra-high-performance liquid chromatography identified the phenolic profile. The in vitro anticancer activity was evaluated using the MTT assay on HL-60 and K-562 myeloleukemia cells and liver (Huh-7) cell lines. The anti-inflammatory effect was assessed in vivo using carrageenan-induced paw edema in rats. The hepatoprotective effect at 300 and 1000 mg/kg doses against the acetaminophen-induced hepatotoxicity on rats was studied for seven days. Additionally, molecular docking simulations were performed to evaluate the extract's inhibitory potential against key targets: lipoxygenase, cytochrome P450, tyrosine kinase, and TRADD. The extract exhibited significant cytotoxic activity against K-562 and HL-60 cells, but not against lung cancer cells (Huh-7 line). The 1000 mg/kg dose demonstrated the most potent anti-inflammatory effect, inhibiting edema by 99.10% after 6 h. C. monogyna extract displayed promising hepatoprotective properties. Procyanidin (-7.27 kcal/mol), quercetin (-8.102 kcal/mol), and catechin (-9.037 kcal/mol) were identified as the most active molecules against lipoxygenase, cytochrome P450, and tyrosine kinase, respectively. These findings highlight the untapped potential of C. monogyna for further exploration in treating liver damage, inflammation, and leukemia.

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.

Medicinal and cosmetic use of plants from the province of Taza, Northern Morocco / Uso medicinal y cosmético de las plantas de la provincia de Taza, Norte de Marruecos

This work aims to make an inventory of plants and their medicinal and cosmetic uses in the Pre-Rif (foothills of the Rif, a massif in Northern Morocco) of the province of Taza. Following ethnobotanical investigations, carried out with the local population and field surveys, 73 plant species used locally in traditional medicine have been identified, as well as six species which have ethno-veterinary properties. They belong to 39 botanical families and were collected essentially in the study area. Most remedies are prepared as decoctions (40 species) or with an aqueous base (infusion, aqueous macerate-8 species); more species are used for internal or oral administration (61 species) compared with external or local ones (27 species). These plants, 14.8 percent of which are central to herbalists’ activity in the region, are widely used in indigenous pharmacopoeia to treat common symptoms, such as gastrointestinal disorders (33 species), articular-system disruption, ENT (Ear, Nose and Throat) diseases and headaches (24 species), and skin problems (11 species). Moreover, 13 species in particular are used by women for cosmetic purposes. The local population uses medicinal plant species for daily care which may increase the pressure on natural resources, e.g. vulnerable species such as Origanum compactum and Rosmarinus officinalis. Hence, the adoption of a sustainable-management approach to safeguard and preserve the local medicinal flora is urgent.

El propósito de este trabajo es el de realizar un inventario de plantas, sus usos medicinales y cosméticos en el Pre-Rif (estribaciones del Rif, un macizo en el norte de Marruecos) de la provincia de Taza. A partir de investigaciones etnobotánicas realizadas con la población local y de estudios de campo, se han identificado 73 especies de plantas (pertenecientes a 39 familias), utilizadas localmente en la medicina tradicional, seis de las cuales tienen además usos etno-veterinarios. La mayor parte de estas especies fueron recolectadas en la región. La mayoría de los remedios se preparan en decocciones (40 especies), o con una base acuosa (infusión, maceración acuosa - 8 especies). Del mismo modo, la mayor parte de las especies se administran por vía oral o interna (61 especies), en comparación con aquellas aplicadas de modo externo o local (27 especies). Estas plantas, 14,8 por ciento de las cuales son en el centro de la actividad de los herbolarios de la región, son ampliamente utilizadas en la farmacopea indígena para atenuar síntomas comunes, tales como trastornos gastrointestinales (33 especies), alteraciones articulares, enfermedades otorrinológicas (oído, nariz y garganta), dolores de cabeza (24 especies) y problemas de la piel (11 especies). Además, 13 especies son especialmente utilizadas por las mujeres para fines cosméticos. El uso cotidiano de la población local de estas especies medicinales podría acentuar la presión sobre los recursos naturales, es decir, las especies vulnerables tales como Origanum compactum y Rosmarinus officinalis. Por lo tanto, es urgente gestionar un manejo sostenible de estos recursos de modo de garantizar su protección y preservación.

Socioeconomic interest and valorization of medicinal plants from the Rissani oasis (SE of Morocco) / Interés socioeconómico y valorización de plantas medicinales del oasis de Rissani (SE de Marruecos)

The survival and sustenance of man depends largely on plants which generate directly 87 percent of its food needs and constitute a source of basic health care in developing countries. Based on socio-economic surveys and field observations led in the Rissani oasis (SE of Morocco), we have identified 109 species belonging to 45 botanical families and 102 genera. The distribution in families is: Lamiaceae (15.2 percent, Asteraceae (11.5 percent), Fabaceae (8.46 percent, Poaceae (8.12 percent) and Apiaceae (6.75 percent). The species used in traditional medicine correspond to 57.8 percent, for food 10.1 percent and for other uses 28.4 percent. Of these species, 10.1 percent are cultivated, naturalized, introduced and/or weeds. Byproducts of 46.8 percent of these species are imported from other regions of Morocco and locally marketed. Many medicinal species from this area are not recognized by the inhabitants, and their sensitization towards the use and conservation of local plant diversity is needed.

La supervivencia y sustentabilidad de la humanidad depende en gran medida de las plantas. Estas satisfacen directamente el 87 por ciento de sus necesidades alimenticias y constituyen, en países en desarrollo, una fuente para el cuidado de salud. Basados en estudios y observaciones de campo realizadas en el oasis de Rissani (SE de Marruecos), hemos identificado las 109 especies de plantas más utilizadas que pertenecen a 45 familias y 102 géneros. La distribución por familia es: Lamiaceae (15.2 por ciento), Asteraceae (11.5 por ciento), Fabaceae (8.46 por ciento), Proaceae (8.12 por ciento) y Apiaceae (6.75 por ciento). Las especies utilizadas en medicina tradicional corresponden al 57.8 por ciento, en alimentación 28.5 por ciento y para usos múltiples 28.4 por ciento. De estas especies el 10.1 por ciento son cultivadas, naturalizadas, introducidas y/o corresponden a malezas. Subproductos del 48.8 por ciento de estas especies son importados de otras regiones de Marrueco para su comercialización. Muchas de las especies medicinales no son reconocidas por los habitantes del oasis y es necesario sensibilizarlos en relación a su utilización y conservación.