Evaluation of medicinal plants from Morocco as novel source of anti-parasitic agents.

La aparición de la resistencia a los antimicrobianos es un enorme problema de salud pública que hace urgente el desarrollo de nuevas moléculas bioactivas. En este contexto, las plantas que supuestamente curan las infecciones cutáneas se seleccionan entre los herbolarios de la región de Fez-Meknes y las seleccionadas se someten a un fraccionamiento bioguiado para identificar los compuestos activos frente a Leishmania spp. y Staphylococcus aureus frecuentemente aislados en este tipo de patología en el área estudiada. Se enumeran 64 plantas, 15 especies que mostraron un índice de frecuencia de citas alto y una contribución bibliográfica baja para cada germen objetivo se evalúan por sus propiedades antimicrobianas. La prueba cualitativa utilizando el ensayo de macrodilución en agar reveló que el extracto etanólico de Rhamnus alaternus es el más activo contra las cepas de S. aureus, mientras que el ensayo de microdilución mostró que el extracto etanólico de Inula viscosa es el más activo contra Leishmania spp .. El fraccionamiento bioguiado, los análisis espectroscópicos y espectrométricos (RMN, EIMS y HREIMS) del extracto de Rhamnus alaternus dieron como compuestos activos emodina y kaempferol. Sin embargo, se encontró que la emodina era la más activa contra las cepas de S. aureus con valores de CMI de 1,93 y 15,63 μg / ml y CC50> 100 μg/ml, lo que refleja la no toxicidad de este compuesto. El fraccionamiento bioguiado del extracto de Inula viscosa a través de múltiples pasos cromatográficos que involucran gel de sílice y columnas sephadex LH-20, cromatografía plana y centrífuga preparativa permitió identificar mediante análisis espectroscópicos y de correlación (RMN, HMBC, HSQC y ROESY) ocho compuestos, entre los cuales cuatro (8-epi-xantatina-1β, 5β-epóxido e inuloxina A, sakuranetina y taxifolina) fueron las más activas contra las especies objetivo, Leishmania amazonensis y Leishmania donovani con IC50 entre 9.53 y 86.45 µM para promastigotes, y entre 0.64 y 6.98 µM para amastigotes. Se evaluó la citotoxicidad de los cuatro compuestos en una línea celular de macrófagos murinos (J774A.1) y el ensayo fluorimétrico usando el reactivo AlamarBlue mostró que los compuestos no son tóxicos a la dosis probada. Estos cuatro compuestos anti-Leishmania también fueron activos contra Trypanosoma cruzi, mientras que Naegleria fowleri fue susceptible únicamente a la inuloxina A. El mecanismo de acción de estos cuatro compuestos se ha dilucidado utilizando la viabilidad celular y kits para la detección de eventos de apoptosis. Los resultados obtenidos mostraron que estos compuestos indujeron eventos de tipo apoptótico en L. amazonensis, L. donovani, T. cruzi y N. fowleri por alteración de la permeabilidad de la membrana (kit SYTOX Green), condensación de cromatina (kit doble Hoechst33342 / PI), disrupción de función mitocondrial (sonda JC-1) y disminución de los niveles de producción de ATP (CellTiter-Glo) además de la regeneración de ROS (kit CellROX) en L. amazonensis, T. cruzi y N. fowleri

IN VITRO ANTIBACTERIAL ACTIVITY OF MEDICINAL PLANTS IN THE CENTRAL NORTH OF MOROCCO: A POSSIBLE SOURCE OF ALTERNATIVE DRUGS AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

Objective: The present study aims the investigation of the antimicrobial potential of medicinal plants selected in the central north of Morocco against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis strain often involved in dermatitis. Methods: Structured interviews were carried out among 91 herbalists and traditional healers through a specific information questionnaire, the in vitro susceptibility of Staphylococcus strains award ethanol extracts was evaluated using the well-diffusion assay, while the agar-microdilution method was used to determinate the minimal inhibitory concentrations (MIC). The total phenolic and flavonoids contents of all tested extracts were also determined. Results: Based on the ethnobotanical survey, a total of 55 plant species belonging to 30 families were mentioned. The Lamiaceae family was the most represented (18.80%) followed by the Apiaceae family (10.90%). Leaves (45.00%) were the favored used part. Decoction method (48.53%) was the most frequently used to prepare remedies that are taken externally (75.00%). Nine of the 17 most selected species have shown an effective antistaphylococcal activity; the most active extracts were Punica granatum and Rhamnus alaternus with MIC values ranging between 0.25 mg/ml and 2.00 mg/ml. Conclusion: The current data confirm the good antistaphylococcal activity of P. granatum and R. alaternus and suggest that these species could constitute a promoter source for antistaphylococcal drugs with deeply studies

Pharmacological Effects of Grifolin: Focusing on Anticancer Mechanisms

Grifolin is a volatile compound contained in essential oils of several medicinal plants. Several studies show that this substance has been the subject of numerous pharmacological investigations, which have yielded interesting results. Grifolin demonstrated beneficial effects for health via its multiple pharmacological activities. It has anti-microbial properties against bacteria, fungi, and parasites. In addition, grifolin exhibited remarkable anti-cancer effects on different human cancer cells. The anticancer action of this molecule is related to its ability to act at cellular and molecular levels on different checkpoints controlling the signaling pathways of human cancer cell lines. Grifolin can induce apoptosis, cell cycle arrest, autophagy, and senescence in these cells. Despite its major pharmacological properties, grifolin has only been investigated in vitro and in vivo. Therefore, further investigations concerning pharmacodynamic and pharmacokinetic tests are required for any possible pharmaceutical application of this substance. Moreover, toxicological tests and other investigations involving humans as a study model are required to validate the safety and clinical applications of grifolin

From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances

The emergence of a novel human coronavirus (SARS-CoV-2) causing severe contagious respiratory tract infections presents a serious threat to public health worldwide. To date, there are no specific antiviral agents available for this disease, currently known as COVID-19. Therefore, genomic sequencing and therapeutic clinical trials are being conducted to develop effective antiviral agents. Several reports have investigated FDA-approved drugs as well as in silico virtual screening approaches such as molecular docking and modeling to find novel antiviral agents. Until now, antiparasitic drugs such as chloroquine have shown the most relevant results. Furthermore, there is an urgent need to understand the pathogenesis of this novel coronavirus, its transmission routes, surface survival and evolution in the environment. So far, the scientific community has indicated a possible transmission of COVID-19 via blood transfusion which is challenging in the case of asymptomatic individuals. Protocols for pathogen inactivation are also needed. In this paper, we reviewed recent findings about this life-threatening pandemic

Susceptibility patterns of bacteria isolated from the hospital environment towards disinfectants commonly used for surfaces and medical devices

This study aimed to evaluate the bactericidal activity of common disinfectants used for surfaces and medical devices. Sodium hypochlorite (D1), disinfectant (D2) composed of N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine, chloride de didecyldimethylammonium, and disinfectant (D3) composed of Didecyldimethylammonium chloride and Polyhexamethylene biguanide hydrochloride, were tested against 15 strains isolated from the hospital environment and four reference bacteria. The microdilution method was performed to assess antimicrobial activity. The susceptibility was evaluated by comparing the minimum inhibitory dilution with the dilution of disinfectant recommended by the manufacture. D1 and D2 were active against Staphylococcus epidermidis, Staphylococcus saprophyticus, Enterobacter cloacae, Escherichia coli, Pseudomonas fluorescens, Methicillin-resistant Staphylococcus aureus, Bacillus spp, Corynebacterium spp, Gram-positive bacillus, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 3366, and Pseudomonas aeruginosa ATCC 27853 strains but not active against Micrococcus spp, and Staphylococcus aureus ATCC 29213. D3 was ineffective against Micrococcus spp, Bacillus Gram Positive, Staphylococcus epidermidis, and Escherichia coli ATCC 25922. Therefore, D1 and D2 can eliminate most pathogenic bacteria in hospitals, in comparison to D3. It is necessary to monitor the antibacterial activity of disinfectants against reference strains but also against those usually present on surfaces. The obtained results could have promising applications in controlling the emergence of nosocomial infections

Bioguided Isolation of Active Compounds from Rhamnus alaternus against Methicillin-Resistant Staphylococcus aureus (MRSA) and Panton-Valentine Leucocidin Positive Strains (MSSA-PVL)

Despite intensified efforts to develop an effective antibiotic, S. aureus is still a major cause of mortality and morbidity worldwide. The multidrug resistance of bacteria has considerably increased the difficulties of scientific research and the concomitant emergence of resistance is to be expected. In this study we have investigated the in vitro activity of 15 ethanol extracts prepared from Moroccan medicinal plants traditionally used for treatment of skin infections. Among the tested species I. viscosa, C. oxyacantha, R. tinctorum, A. herba alba, and B. hispanica showed moderate anti-staphylococcal activity. However, R. alaternus showed promising growth-inhibitory effects against specific pathogenic bacteria especially methicillin-susceptible Staphylococcus aureus Panton-Valentine leucocidin positive (MSSA-PVL) and methicillin-resistant S. aureus (MRSA). The bioguided fractionation of this plant using successive chromatographic separations followed by nuclear magnetic resonance (NMR) and mass spectrometry (MS) including EIMS and HREIMS analysis yielded the emodin (1) and kaempferol (2). Emodin being the most active with MICs ranging between 15.62 and 1.95 µg/mL and showing higher activity against the tested strains in comparison with the crude extract, its mechanism of action and the structure-activity relationship were interestingly discussed. The active compound has not displayed toxicity toward murine macrophage cells. The results obtained in the current study support the traditional uses of R. alaternus and suggest that this species could be a good source for the development of new anti-staphylococcal agents

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions

Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers