A virtual insight into mushroom secondary metabolites: 3D-QSAR, docking, pharmacophore-based analysis and molecular modeling to analyze their anti-breast cancer potential.

Breast cancer is a major issue of investigation in drug discovery due to its rising frequency and global dominance. Plants are significant natural sources for the development of novel medications and therapies. Medicinal mushrooms have many biological response modifiers and are used for the treatment of many physical illnesses. In this research, a database of 89 macro-molecules with anti-breast cancer activity, which were previously isolated from the mushrooms in literature, has been selected for the three-dimensional quantitative structure-activity relationships (3D-QSAR) studies. The 3D-QSAR model was necessarily used in Pharmacopoeia virtual evaluation of the database to develop novel MCF-7 inhibitors. With the known potential targets of breast cancer, the docking studies were achieved. Using molecular dynamics simulations, the targets' stability with the best-chosen natural product molecule was found. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity of three compounds, resulting after the docking study, were predicted. The compound C1 (Pseudonocardian A) showed the features of effective compounds because it has bioavailability from different coral species and is toxicity-free for the prevention of many dermatological illnesses. C1 is chemically active and possesses charge transfer inside the monomer, as seen by the band gaps of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) electrons. The reactivity descriptors ionization potential, electron affinity, chemical potential (µ), hardness (η), softness (S), electronegativity (χ), and electrophilicity index (ω) have been estimated using the energies of frontier molecular orbitals (HOMO-LUMO). Additionally, molecular electrostatic potential maps were created to show that the C1 is reactive.Communicated by Ramaswamy H. Sarma.

The selected compounds from the mushroom were evaluated as potential breast cancer MCF-7 cell line inhibitor.Ligand-based 3D-QSAR study to analyze the structurally diverse compounds with experimentally reported IC₅₀.Pharmacophore-based virtual screening of compounds.Molecular docking analysis pointed out the vital interaction of the hit with the protein's amino acids.Absorption, distribution, metabolism, and excretion (ADME) and toxicity properties of the lead compounds were examined.

Exploring potent aldose reductase inhibitors for anti-diabetic (anti-hyperglycemic) therapy: integrating structure-based drug design, and MMGBSA approaches.

Aldose reductase (AR) is an important target in the development of therapeutics against hyper-glycemia-induced health complications such as retinopathy, etc. In this study, we employed a combination of structure-based drug design, molecular simulation, and free energy calculation approaches to identify potential hit molecules against anti-diabetic (anti-hyperglycemic)-induced health complications. The 3D structure of aldoreductase was screened for multiple compound libraries (1,00,000 compounds) and identified as ZINC35671852, ZINC78774792 from the ZINC database, Diamino-di nitro-methyl dioctyl phthalate, and Penta-o-galloyl-glucose from the South African natural compounds database, and Bisindolylmethane thiosemi-carbazides and Bisindolylme-thane-hydrazone from the Inhouse database for this study. The mode of binding interactions of the selected compounds later predicted their aldose reductase inhibitory potential. These com-pounds interact with the key active site residues through hydrogen bonds, salt bridges, and π-π interactions. The structural dynamics and binding free energy results further revealed that these compounds possess stable dynamics with excellent binding free energy scores. The structures of the lead inhibitors can serve as templates for developing novel inhibitors, and in vitro testing to confirm their anti-diabetic potential is warranted. The current study is the first to design small molecule inhibitors for the aldoreductase protein that can be used in the development of therapeutic agents to treat diabetes.

Molecular Characterization of Gene-Mediated Resistance and Susceptibility of ESKAPE Clinical Isolates to Cistus monspeliensis L. and Cistus salviifolius L. Extracts.

Background: Multidrug resistance (MDR) and extensively drug-resistant (XDR) are now the biggest threats to human beings. Alternative antimicrobial regimens to conventional antibiotic paradigms are extensively searched. Although Cistus extracts have long been used for infections in traditional folk medicines around the world, their efficacy against resistant bacteria still needs to be elucidated. We aim to investigate the antibiotic susceptibility profiles of clinical strains Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (acronym "ESKAPE"), and their resistance mechanisms by PCR, as well as their sensitivity to C. monspeliensis (CM) and C. salviifolius (CS) methanol extracts and their fractions. Methods: Antibiotic susceptibility profile and resistance mechanism were done by antibiogram and PCR. Fractions of CM and CS were obtained using maceration and Soxhlet; their antibacterial activities were evaluated by determining inhibition zone diameter (IZD), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Results: Results revealed that all strains were XDR except S. aureus, which was MDR. The PCR indicates the presence of gene-mediated resistance (bla CTX-M, bla SHV, bla OXA-48, bla NDM, bla OXA-51, bla OXA-58, bla IMP, bla VIM, and bla mecA). Also, maceration was slightly better for bioactivity preservation. Overall, the extracts of CM (IZD = 20 mm, MIC = 0.01 mg/mL) were more active than those of CS. All extracts inhibited MRSA (methicillin-resistant Staphylococcus aureus) and ERV (Enterococcus faecium Vancomycin-Resistant) with interesting MICs. The ethyl acetate fraction manifested great efficacy against all strains. Monoterpene hydrocarbons and sesquiterpenes oxygenated were the chemical classes of compounds dominating the analyzed fractions. Viridiflorol was the major compound in ethyl acetate fractions of 59.84% and 70.77% for CM and CS, respectively. Conclusions: The superior activity of extracts to conventional antibiotics was seen for the first time in the pathogens group, and their bactericidal effect could be a promising alternative for developing clinical antibacterial agents against MDR and XDR ESKAPE bacteria.

Ethnobotanical Study of Medicinal Plants Used as Therapeutic Agents to Manage Diseases of Humans.

OBJECTIVE: This work aimed to survey medicinal plants used in phytotherapy in the Fez-Boulemane region, Morocco. METHODS: A comprehensive ethnobotanical survey was conducted using a questionnaire to collect data from thirty herbalists on medicinal plants used for therapeutic purposes in the Fez-Boulemane region, Morocco. RESULTS: The mean age of herbalists interviewed was 52.13 years. Forty percent of the herbalists were illiterate, and 73% referred to the experiences of their parents as knowledge of the properties and uses of medicinal plants. One hundred and eight medicinal plants belonging to 51 botanical families were recommended by herbalists in the region of Fez-Boulemane, Morocco, for treatment. According to the respondents, Lawsonia inermis L., Rosmarinus officinalis L., and Lavandula coronopifolia L. were the most used plants with the percentage of 13%, 12%, and 11%, respectively. Most plants had been involved in the treatment of digestive disorders (25%) and osteoarticular diseases (24%). Some (7.4%) of the plants mentioned in our survey were potentially toxic. CONCLUSION: It was learned that irrational use of toxic plants and unknown compositions of recipes are recommended to consumers. As a result, particular attention should be paid to risks related to plants used in traditional treatment without scientific validation. It is envisaged that increasing awareness, by conducting educational campaigns and transferring evidence-based scientific knowledge, on traditional treatments among the local population is expected to have beneficial impacts on health and disease management.

Effects of Different Solvents Extractions on Total Polyphenol Content, HPLC Analysis, Antioxidant Capacity, and Antimicrobial Properties of Peppers (Red, Yellow, and Green (Capsicum annum L.)).

Plants possessing various bioactive compounds and antioxidant components have gained enormous attention because of their efficacy in enhancing human health and nutrition. Peppers (Capsicum annuum L.), because of their color, flavor, and nutritional value, are considered as one of the most popular vegetables around the world. In the present investigation, the effect of different solvents extractions (methanol, ethanol, and water) and oven drying on the antioxidant and antimicrobial properties was studied of red, yellow, and green peppers. The green pepper water extract showed the highest total polyphenol content (30.15 mg GAE/g DW) followed by red pepper water extract (28.73 mg GAE/g DW) and yellow pepper water extract (27.68 mg GAE/g DW), respectively. The methanol extracts of all the pepper samples showed higher TPC as compared to the ethanol extract. A similar trend was observed with the total flavonoid content (TFC). The antioxidant assays (DPPH scavenging and reducing power) echoed the findings of TPC and TFC. In both antioxidant assays, the highest antioxidant activity was shown by the water extract of green pepper, which was followed by the water extract of red pepper and yellow pepper. Furthermore, all extracts were assessed for their potential antimicrobial activity against bacterial and fungal pathogens. Aqueous extracts of all three pepper samples exhibited slightly higher inhibition zones as compared to their corresponding ethanolic and methanolic extract. Minimum inhibitory concentration (MIC) values ranged from 0.5 to 8.0 mg/ml. The lowest MIC values ranging from 0.5 to 2.0 mg/ml concentration were recorded for aqueous extracts of green pepper. High-performance liquid chromatography (HPLC) analysis revealed tannic acid as the major phenolic compound in all three pepper samples. Thus, it is envisaged that the microwave drying/heating technique can improve the antioxidant and antimicrobial activity of the pepper.

Quantification of Chlorogenic Acid and Vanillin from Coffee Peel Extract and its Effect on α-Amylase Activity, Immunoregulation, Mitochondrial Oxidative Stress, and Tumor Suppressor Gene Expression Levels in H2O2-Induced Human Mesenchymal Stem Cells.

Background: Polyphenols and flavonoid-rich foods help in arresting reactive oxygen species development and protecting DNA from oxidative damage. Coffee peel (CP) preparations are consumed as beverages, and their total polyphenol or flavonoid content and their effect on oxidative stress-induced human mesenchymal stem cells (hMSCs) are poorly understood. Method: We prepared hot water extracts of CP (CPE) and quantified the amount of total polyphenol and flavonoid using HPLC analysis. In addition, CPE have been studied for their α-amylase inhibitory effect and beneficial effects in oxidative stress-induced hMSCs. Results: The obtained results show that the availability of chlorogenic acid, vanillin, and salicylic acid levels in CPE is more favorable for enhancing cell growth, nuclear integrity, and mitochondrial efficiency which is confirmed by propidium iodide staining and JC-1 staining. CPE treatment to hMSCs for 48 h reduced oxidative stress by decreasing mRNA expression levels of LPO and NOX-4 and in increasing antioxidant CYP1A, GSH, GSK-3ß, and GPX mRNA expressions. Decreased pro-inflammatory (TNF-α, NF-κß, IL-1ß, TLR-4) and increased tumor suppressor genes (except Bcl-2) such as Cdkn2A, p53 expressions have been observed. Conclusions: The availability of CGA in CPs effectively reduced mitochondrial oxidative stress, reduced pro-inflammatory cytokines, and increased tumor suppressor genes.

Effect of Microwave Roasting and Extraction Solvents on the Bioactive Properties of Coffee Beans.

Coffee is an intricate mixture of thousands of chemical compounds that are accountable for its flavor and aroma. Roasting is a key step in the processing of coffee beans. This study assessed the effect of microwave roasting (MW) and extraction solvents (ES) on the total polyphenol content, total flavonoid content, and antioxidant activity of coffee beans. The untreated and microwave-roasted (MR) coffee beans showed a total polyphenol content of 40.40 and 35.15 mg GAE/gm DW, respectively, when methanol was used as the solvent for extraction. Similarly, for the untreated coffee beans, the methanol extracted coffee had a significantly (p < 0.05) higher total flavonoid content (39.34 mg CE/g DW) as compared to ethanol (34.82 mg CE/g DW). The obtained IC50 for the untreated and microwave-roasted samples as extracted by methanol were 4.13 and 5.68 mg/mL, respectively, while the IC50 values of untreated and microwave-roasted samples extracted by ethanol were 4.59 and 6.24 mg/mL, respectively. Untreated coffee beans exhibited a higher reducing power (1.237) than that of the microwave-roasted ones (0.839) when extracted with methanol. Chlorogenic acid was the major (2.31-2.68%) phenolic compound found in all the coffee samples whether it was untreated or microwave-roasted. Vanillin demonstrated the lowest (0.118-0.166%) phenolic compound found in the coffee bean samples. These results might be helpful for obtaining the maximum health benefits from coffee.

Chemical Characterization and Antioxidant, Antimicrobial, and Insecticidal Properties of Essential Oil from Mentha pulegium L.

The chemical composition and antibacterial, insecticidal, and antioxidant properties of the essential oil from Mentha pulegium L. (M. pulegium) growing in Morocco were investigated in this work. To achieve this goal, the oils were obtained by using hydrodistillation before being characterized by GC-MS. The antibacterial and antifungal activities were conducted against pathogenic strains using the disc diffusion and MICS bioassays. The insecticidal activity was carried out versus C. maculatus using contact and inhalation tests. The antioxidant activity was performed by using DPPH and total antioxidant capacity bioassays. The chemical analysis of the oil showed that 20 compounds were identified, which represented 98.91% of the total oil. In the oil, the main components detected were R-(+)-pulegone (76.35%), carvone (5.84%), dihydrocarvone (5.09%), and octanol-3 (2.25%). The essential oil has moderate-to-strong broad-spectrum antibacterial and antifungal properties; the results showed that B. subtilis was the most sensitive strain to M. pulegium oil, with the largest inhibition diameter (25 ± 0.33). For the antifungal activity, the results obtained indicated that Aspergillus niger was the most sensitive fungal strain to M. pulegium oil with an inhibition percentage up to 100%. Regarding the insecticidal activity, the inhalation test showed a high efficacy (100% mortality), and a lethal concentration of LC50 = 1.41 + 0.48 µL/L air was obtained after 24 hours of exposure. Moreover, the contact test showed that a total reduction in fertility and emergence was obtained with a dose of 20 µL/mL of acetone. Regarding the antioxidant activity, the sample concentration necessary to inhibit 50% of HE radicals (IC50) was 7.659 mg/mL (DPPH) and 583.066 57.05 mg EAA/g EO (TAC).

Traditional medicinal knowledge of plants used for cancer treatment by communities of mountainous areas of Fez-Meknes-Morocco.

Since their existence on earth, humans have used herbal medicine to meet their requirements for medication. The aim of the study: This work refers to a study conducted to carry out an ethnopharmacological survey of medicinal plants used for the treatment of cancer in Fez-Meknes region of Morocco. Material and Methods: To achieve this goal, 300 informants including 237 local people and 63 herbalists. They were requested to fill a survey related questionnaire aiming at the collection of data about the addressed objective. Informants were asked about the vernacular names, parts of medicinal plants used, mode of preparation, route of administration, reference area as well as the ecological distribution. The Relative Frequency of Citation (RFC) and Fidelity Level (FL) were calculated to identify the most effective plants recommended by informants for disease treatment. Results: The findings obtained in the present survey revealed that 94 species belonging to 47 families have been used for cancer treatment in the region of Fez-Meknes. Fruits, leaves, and seeds are the most commonly used plant parts, by the time powder and infusion arethe most common methods used fordrug preparations. Conclusion: This work may contribute towards the society as it provides interesting data on traditional medicinal knowledge of medicinal plantsused to fight cancer.

Phytochemistry and Pharmacology of Thymus broussonetii Boiss.

Thymus broussonetii Boiss (T. broussonetii) is a rare medicinal and aromatic plant. It is widely used in traditional medicine to treat several diseases, including diarrhea, fever, cough, irritation, skin diseases, rheumatism, respiratory ailments, influenza, and digestion problems. In this review, we have critically summarized previous data on T. broussonetii about its phytochemistry, botanical and geographical distribution, toxicological investigation, and pharmacological properties. Using scientific research databases such as Wiley Online, SciFinder, ScienceDirect, PubMed, SpringerLink, Web of Science, Scopus Wiley Online, and Google Scholar, the data on T. broussonetii were collected and discussed. The presented data regrouped bioactive compounds and biological activities of T. broussonetii. The findings of this work showed that essential oils and extracts of T. broussonetii exhibited numerous pharmacological activities (in vitro and in vivo), particularly antibacterial, antifungal, antioxidant, anticancer, anti-inflammatory, insecticidal, antipyretic, antinociceptive, and immunological and behavioral effects. While toxicological studies of T. broussonetii essential oils and extracts are lacking, modern scientific tools revealed the presence of different classes of secondary metabolites such as terpenoids, alkaloids, flavonoids, tannins, coumarins, quinones, carotenoids, and steroids. T. broussonetii essential oils, especially from the aerial parts, exhibited potent antibacterial, antifungal, and antioxidant effects. An in-depth toxicological investigation is needed to validate the efficacy and safety of T. broussonetii extracts and essential oils and their secondary metabolites. However, further pharmacokinetic and pharmacodynamic studies should be performed to validate its bioavailability.