Ethnobotanical study of medicinal plants used for cancer treatment at the province of Nador, Morocco

Morocco has varied wealth of aromatic and medicinal plants (AMPs) which are commonly used for prevention and treatment of vario us diseases or as complementary therapy such for cancer diseases. An ethnobotanical study was carried out in the province of Nador, located northeast of Morocco. A total of 418 persons were interviewed, information about their profile, type of medicinal pl ants existing in this area, plant characteristics and uses of those existing plants. Results showed 35 species distributed in 23 families, the most represented were Lamiaceae (7), Apiaceae (5) and Fabaceae (3). This study revealed that the population mainl y used seeds (28%), leaves (26%), aerial parts (20%) and fruits (14%). Moreover, it has shown that Nerium oleander were used by the local population for cancer treatments. Biological activity of N. oleander showed an antimicrobial effect on Escherichia col i , Pseudomonas aeruginosa and Staphylococcus aureus

Marruecos tiene una riqueza vegetal muy variada de plantas aromáticas y medicinales (AMP) y se utilizan com únmente para la prevención y el tratamiento de diversas enfermedades o como terapia complementaria, como las enfermedades del cáncer. Se llevó a cabo un estudio etnobotánico en la provincia de Nador, situada al noreste de Marruecos. Se entrevistó a un tota l de 418 personas, información sobre su perfil, tipo de plantas medicinales existentes en esta zona, características de las plantas, usos de las plantas existentes, etc. Los resultados mostraron una alta riqueza de especies de 35 especies distribuidas en 2 3 familias, las más representadas fueron Lamiaceae (7), Apiaceae (5) y Fabaceae (3). Este estudio reveló que la población utilizó preferentemente semillas (28%), hojas (26%), partes aéreas (20%) y frutos (14%). Además, se ha demostrado que la población loc al utilizaba Nerium oleander para tratamientos contra el cáncer. La actividad biológica de N. oleander mostró un efecto antimicrobiano sobre Escherichia coli , Pseudomonas aeruginosa y Staphylococcus aureus

Unlocking the plant growth-promoting potential of yeast spp.: exploring species from the Moroccan extremophilic environment for enhanced plant growth and sustainable farming.

In this study, we successfully isolated two distinct yeasts from Moroccan extreme environments. These yeasts were subjected to molecular characterization by analyzing their Internal Transcribed spacer (ITS) regions. Our research thoroughly characterizes plant growth-promoting abilities and their drought and salt stress tolerance. In a greenhouse assay, we examined the impact of selected yeasts on Medicago sativa's growth. Four treatments were employed: (i) control without inoculation (NI), (ii) inoculation with L1, (iii) inoculation with L2, and (iv) inoculation with the mixture L1 + L2. L1 isolated from Toubkal Mountain shared 99.83% sequence similarity to Rhodotorula mucilaginosa. Meanwhile, L2, thriving in the arid Merzouga desert, displayed a similar identity to Naganishia albida (99.84%). Yeast strains were tolerant to NaCl (2 M) and 60% PEG (polyethylene glycol P6000) in case of drought. Both strains could solubilize phsphorus, with L2 additionally demonstrating potassium solubilization. In addition, both strains produce indole acetic acid (up to 135 µl ml-1), have siderophore ability, and produce aminocyclopropane-1-carboxylic acid deaminase. Isolates L1 and L2, and their consortium showed that the single or combined strain inoculation of M. sativa improved plant growth, development, and nutrient assimilation. These findings pave the way for harnessing yeast-based solutions in agricultural practices, contributing to enhanced crop productivity and environmental sustainability.

New Insights on the Progesterone (P4) and PGRMC1/NENF Complex Interactions in Colorectal Cancer Progression.

The literature data regarding the risk of colorectal cancer (CRC) in the context of hormone therapy (HT), including both estrogen-progestogen combinations and estrogen alone, are inconclusive. The precise relationship underlying the action of progesterone (P4) and progesterone receptors in CRC has yet to be determined. We characterized the expression profiles of both nuclear and membrane progesterone receptors and their potential cofactors in CRC tissues. Additionally, we analyzed the P4 and NENF treatment effects on the cell proliferation and invasion of DLD-1 and HT-29 colorectal cancer cells. We observed a weak expression of the nuclear P4 receptor (PGR), but an abundant expression of the P4 receptor membrane component 1 (PGRMC1) and neuron-derived neurotrophic factor (NENF) in the CRC tissues. P4 treatment stimulated the proliferation of the DLD-1 and HT-29 CRC cells. The co-treatment of P4 and NENF significantly increased the invasiveness of the DLD-1 and HT-29 cells. A functional analysis revealed that these effects were dependent on PGRMC1. AN immunocytochemical analysis demonstrated a cytoplasmic co-localization of PGRMC1 and NENF in the CRC cells. Moreover, the concentration of serum NENF was significantly higher in CRC patients, and P4 treatment significantly increased the release of NENF in the DLD-1 cells. P4 or NENF treatment also significantly increased the IL-8 release in the DLD-1 cells. Our data may provide novel insights into the action of P4 and PGRMC1/NENF in CRC progression, where NENF may act as a potential PGRMC1 co-activator in non-classical P4 signaling. Furthermore, NENF, as a secreted protein, potentially could serve as a promising circulating biomarker candidate for distinguishing between colorectal cancer patients and healthy individuals, although large-scale extensive studies are needed to establish this.

Chemical Composition and In Vitro Antioxidant and Antimicrobial Activities of the Marine Cyanolichen Lichina pygmaea Volatile Compounds.

Volatile compounds from the marine cyanolichen Lichina pygmaea, collected from the Moroccan Atlantic coast, were extracted by hydrodistillation and their putative chemical composition was investigated by gas chromatography coupled to mass spectrometry (GC/MS). Based on the obtained results, Lichina pygmaea volatile compounds (LPVCs) were mainly dominated by sesquiterpenes compounds, where γ-himachalene, ß-himachalene, (2E,4E)-2,4 decadienal and α-himachalene were assumed to be the most abundant constituents, with percentage of 37.51%, 11.71%, 8.59% and 7.62%, respectively. LPVCs depicted significant antimicrobial activity against all tested strains (Staphylococcus aureus CCMM B3, Pseudomonas aeruginosa DSM 50090, Escherichia coli ATCC 8739 and Candida albicans CCMM-L4) with minimum inhibitory concentration (MIC) values within the range of 1.69-13.5 mg/mL. Moreover, this LPVC showed interesting scavenging effects on the 2,2-diphenyl-1-picrylhydrazyl radical with an IC50 of 0.21 mg/mL. LPVCs could be an approving resource with moderate antimicrobial potential and interesting antioxidant activity for cosmetics and pharmaceutical applications.

New Insight into the Chemical Composition, Antimicrobial and Synergistic Effects of the Moroccan Endemic Thymus atlanticus (Ball) Roussine Essential Oil in Combination with Conventional Antibiotics.

This study reported the volatile profile, the antimicrobial activity and the synergistic potential of essential oil (EO) from the Moroccan endemic Thymus atlanticus (Ball) Roussine, in combination with the antibiotics ciprofloxacin and fluconazole for the first time, to the best of our knowledge. The EO chemical composition was determined by gas chromatography coupled to mass spectrometry (GC-MS) analysis and the antimicrobial activity assessed by the disc diffusion method against three Gram positive (Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus) and three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and one clinical isolate, Klebsiella pneumonia). The antifungal activity was evaluated in four pathogenic yeasts (Candida albicans, C. glabrata, C. krusei and C. parapsilosis). The minimum inhibition concentration (MIC) and the synergistic effect with ciprofloxacin and fluconazole were determined by the two-fold dilution technique and checkerboard test, respectively. Twenty-one constituents were identified by GC-MS in the EO, including carvacrol (21.62%) and borneol (21.13%) as the major components. The EO exhibited a significant antimicrobial activity with inhibition zones ranging from 0.7 mm to 22 mm for P. aeruginosa and B. subtilis, respectively, and MIC values varying from 0.56 mg/mL to 4.47 mg/mL. The fractional inhibitory concentration index (FICI) values ranged from 0.25 to 0.50 for bacteria and from 0.25 to 0.28 for yeasts. The maximum synergistic effect was observed for K. pneumonia with a 256-fold gain of antibiotic MIC. Our results have suggested that EO from T. atlanticus may be used alone or in association with antibiotics as a new potential alternative to prevent and control the emergence of resistant microbial strains both in the medical field and in the food industry.

New insight into antimicrobial activities of Linaria ventricosa essential oil and its synergetic effect with conventional antibiotics.

The purpose of the present study was to determine for the first time the volatile constituents, the antioxidant and antimicrobial activities of the essential oil (EO) of the endemic Moroccan Linaria ventricosa, alone or in combination with four known antibiotics. The major constituents were 2-methoxy-4-vinylphenol (17.4%), α-terpinene (13.64%) and 3,5-dimethylphenyl isocyanate (12.21%). The EO had moderate antioxidant potency, as measured by DPPH free radical scavenging (1.233 ± 0.031 mg/mL), ferric reducing antioxidant power assay (0.373 ± 0.019 mg/mL) and ß-carotene/linoleic acid (0.922 ± 0.026 mg/mL). EO showed microbicidal activity against all microorganisms tested. The highest effectiveness was recorded against Candida albicans (IZ = 24 mm, MIC = 4.87 mg/mL and MMC = 9.75 mg/mL) and Candida glabrata (IZ = 22 mm, MIC = MMC = 4.87 mg/mL). Gram negative bacteria were the most resistant (MIC = MMC = 39 mg/mL). The combination of EO at sub-inhibitory concentrations with antibiotics showed a significant decrease in their individual MICs from 2 to 128 fold, being the best for ciprofloxacin and fluconazole against E. coli and C. albicans and C. glabrata, respectively.

Novel DiOC3 96-well real-time efflux assay for discovery of NorA efflux pump inhibitors in Staphylococcus aureus.

The NorA efflux pump is one of the most studied efflux systems in Staphylococcus aureus and confers multidrug resistance to a variety of dyes and antimicrobial compounds. Hence, inhibition of the NorA efflux pump might be a viable option for restoring susceptibility to antibiotics like fluoroquinolones. Fluorescent real-time efflux assays are important tools to identify putative efflux pump inhibitors. Nevertheless, the number of available compounds for usage in Staphylococcus aureus is limited. Previously, a 3-dipropyloxacarbocyanine iodide (DiOC3) efflux assay was published that circumvented problems associated with the usage of ethidium bromide, namely slow efflux and suggested mutagenicity. However, the DiOC3 assay protocol was cuvette - based and therefore needs to be adapted to the 96-well plate format. Hence, we optimized this assay for usage with 96-well plates. The new assay allows for rapid high-throughput efflux pump inhibitor screening.

Antimicrobial and synergistic effect of Moroccan native Argania spinosa essential oil for modulating of antibiotics resistance.

In this study, the chemical composition and antimicrobial activity of the essential oil (EO) extracted from leaves of the Moroccan endemic plant Argania spinosa were investigated for the first time, to the best of our knowledge. In addition, the EO antimicrobial activity was evaluated in combination with two known antibiotics (ciprofloxacin and fluconazole), in order to ascertain possible synergistic effects. The chemical composition analyzed by GC/MS showed that A. spinosa EO was characterised by the abundance of geranyl acetate (19.18%), methyleugenol (10.98%), linalyl acetate (10.59%) and eucalyptol (8.49%), and monoterpene hydrocarbons was the major class. EO showed an antimicrobial potential against all tested microorganisms. The highest activity was recorded against Gram positive bacteria and yeasts with MICs ranging from 7.75 to 15.5 mg/mL and from 3.88 to 7.75 mg/mL, respectively. The Gram negative bacteria were the most resistant with MICs of 31 mg/mL. The mixture of EO at sub-inhibitory concentrations with conventional drugs exhibited a significant decrease in their individual MICs from 4 to 32 fold. The highest level of synergy was observed for ciprofloxacin against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Despite the antimicrobial activity of A. spinosa EO is weak, the results of the current study suggest a potential synergy between EO and antibiotics in the goal to modulate drug resistance.

A Comparative Study of the in Vitro Antimicrobial and Synergistic Effect of Essential Oils from Laurus nobilis L. and Prunus armeniaca L. from Morocco with Antimicrobial Drugs: New Approach for Health Promoting Products.

Laurus nobilis L. (laurel, Lauraceae) and Prunus armeniaca L. (apricot, Rosaceae) are important industrial crops and display significant biological properties, including antimicrobial activity. In this work, essential oils (EOs) prepared from the leaves of both species from Morocco were evaluated for the first time for possible synergistic in vitro antibacterial and antifungal effects with some conventional antimicrobial drugs, namely fluconazole, ciprofloxacin and vancomycin. Samples were further evaluated for chemical composition by gas chromatography-mass spectrometry (GC-MS). The main volatile compounds detected in L. nobilis were eucalyptol (40.85%), α-terpinyl acetate (12.64%) and methyl eugenol (8.72%), while P. armeniaca was dominated essentially by (Z)-phytol (27.18%), pentacosane (15.11%), nonacosane (8.76%) and benzaldehyde (7.25%). Regarding antimicrobial activity, both EOs inhibited significantly all the microorganisms tested. The EO from L. nobilis had the highest activity, with minimal inhibitory concentrations (MICs) ranging from 1.39 to 22.2 mg/mL for bacteria and between 2.77 and 5.55 mg/mL for yeasts. Conversely, the combination of the studied EOs with ciprofloxacin, vancomycin and fluconazol resulted in a noteworthy decrease in their individual MICs. In fact, of the 32 interactions tested, 23 (71.87%) demonstrated total synergism and 9 (28.12%) a partial synergistic interaction. The EO from L. nobilis exhibited the highest synergistic effect with all the antibiotics used, with fractional inhibitory concentration (FIC) index values in the range of 0.266 to 0.75 for bacteria, and between 0.258 and 0.266 for yeast. The synergistic interaction between the studied EOs and standard antibiotics may constitute promising anti-infective agents useful for treating diseases induced by antibiotic-resistant pathogens.

Draft Genome Sequence of the Novonestmycin-Producing Strain Streptomyces sp. Z26, Isolated from Potato Rhizosphere in Morocco.

Streptomyces sp. strain Z26 exhibited antifungal activity and turned out to be a producer of the secondary metabolites novonestmycin A and B. The 6.5-Mb draft genome gives insight into the complete secondary metabolite production capacity and builds the basis to find and locate the biosynthetic gene cluster encoding the novonestmycins.

Screening for Non-polyenic Antifungal Produced by Actinobacteria from Moroccan Habitats: Assessment of Antimycin A19 Production by Streptomyces albidoflavus AS25.

Fungal diseases are currently a serious public health problem, due to the limited number of fact-based effective principles, and the emergence of resistant strains to the polyenic antifungals. The aim of this study was to screen, for non-polyenic antifungals production by Actinobacteria, and to validate the screening program by characterizingthe produced compounds.Actinobacteria isolates were tested against four clinic human-pathogenic fungi isolated from Hospital Mohammed V Rabat, Morocco. The production of non-polyenic antifungal metabolites by active isolates was investigated based on the yeast cell specificity as challenging targets, antibacterial activity, activity against resistant Candida tropicalis R2 and Pythium irregular (resistant to polyenes), inhibition of antifungal activity by the addition of exogenous ergosterol, and the UV-visible light spectrophotometric analysis of the active crude extracts.The antifungal compound produced was purified using various chromatographic techniques and the selected producing strain was identified using the polyphasic approach.Among 480 Actinobacteria isolates, 55 showed antifungal activity against all tested clinically derived fungi. After performing the screening program, 4 Actinobacteria that hadall the desired criteriawere selected. Using the polyphasic approach, the taxonomic position of the selected Streptomyces AS25, isolated from rhizospheric soil of Alyssum spinosum, showed that it belongs to Streptomyces genus with 100% partial 16S similarity with Streptomyces albidoflavus NBRC13010. On the basis of HPLC and mass spectrometry, the purified compound produced by Streptomyces AS25 was identified as a non-polyenic lactone, antimycin A19, which has been found for the first time to be produced by Streptomyces albidoflavus strain. Following the obtained results, it is important to note that our screening criteria for non-polyenic antifungals have been validated and the rhizospheric soil represents an interesting source to isolate Actinobacteria.

Glyphosate based- herbicide exposure affects gut microbiota, anxiety and depression-like behaviors in mice.

Recently, a number of studies have demonstrated the profound relationship between gut microbiota (GM) alterations and behavioral changes. Glyphosate-based herbicides (GBH) have been shown to induce behavioral impairments, and it is possible that they mediate the effects through an altered GM. In this study, we investigated the toxic effects of GBH on GM and its subsequent effects on the neurobehavioral functions in mice following acute, subchronic and chronic exposure to 250 or 500 mg/kg/day. The effect of these acute and repeated treatments was assessed at the behavioral level using the open field, the elevated plus maze, the tail suspension and splash tests. Then, mice were sacrificed and the intestinal samples were collected for GM analysis. Subchronic and chronic exposure to GBH induced an increase of anxiety and depression-like behaviors. In addition, GBH significantly altered the GM composition in terms of relative abundance and phylogenic diversity of the key microbes. Indeed, it decreased more specifically, Corynebacterium, Firmicutes, Bacteroidetes and Lactobacillus in treated mice. These data reinforce the essential link between GM and GBH toxicity in mice and suggest that observed intestinal dysbiosis could increase the prevalence of neurobehavioral alterations.

Assessment of clinical profile of the patients treated at ayurvedic health facilities in north India.

Since a very long time, a significant number of patients have been seeking treatment at Complementary and Alternative Medicine health facilities, but the disease burden at these facilities has never been assessed and documented. Present cross-sectional study was carried out at Ayurvedic tertiary care hospital to document and to assess the rationale of disease reporting at Ayurvedic institutions of the northern state of India from January 2011 to October 2011. Almost half of the patients' morbidities were not classified at all into any of the disease categories. The common reported morbidities at study hospital were: Respiratory (10.5%), neuromuscular (9.5%), digestive (9.2%) and circulatory (9.1%) disorders. As the majority of diseases were unclassified, so mainstreaming of the effective disease surveillance would be required to understand the morbidity pattern and successful treatment practices at health facilities.

A novel approach of targeted ablation of mammary carcinoma cells through luteinizing hormone receptors using Hecate-CGbeta conjugate.

Recent studies have shown that human and animal mammary gland carcinoma cell line express luteinizing hormone receptors (LHRs). We have examined the cytotoxic effect of Hecate-CGbeta conjugate, that is, fusion of a lytic peptide (Hecate) and a 15-amino acid fragment of the CGbeta-chain in vitro. To test the hypothesis that the Hecate-CGbeta conjugate selectively abolishes cells possessing LHR, estrogen dependent and independent human breast cancer cell lines (MCF-7; MDA-MB-231) and a mouse Leydig tumor cell line (BLT-1) were treated in vitro with Hecate-CGbeta conjugate and Hecate alone. Cytotoxic effects of the Hecate-CGbeta conjugate and the Hecate alone was measured by lactate dehydrogenase (LDH) release immediately after treatment. We observed that the Hecate-CGbeta conjugate selectively, in dose-dependent manner destroys cells possessing LHR in lower concentrations of preparate comparing to the Hecate alone and that the cytotoxic effect is strongly correlated with the number of LHR. Using Western blot analysis we characterized the LHR on membranes of MDA-MB-231, MCF-7 and BLT-1 tumor cell lines. In addition, we showed the evaluation of inhibition potential of the Hecate-CGbeta conjugate to LHR. At a concentration of 33 microM the conjugate inhibited (50%; IC50) the binding of CG to LHR. We suggest further development of this novel approach for the treatment of breast cancer by the Hecate-CGbeta for in vivo trials.