Antimicrobial and antivirulence saponins of Mimusops laurifolia leaves.

Mimusops laurifolia is a native species restricted to the Red Sea mountains and Gulf of Aden. Its leaves contain saponins with wide range of biological activities. The presented research aimed to prepare saponins-rich extract from n-butanol fraction of M. laurifolia leaves and screen it for promising antimicrobial activities. Minimum inhibitory concentration (MIC) of the prepared saponins against Candida albicans, and their potential anti-pathogenic and antivirulence effects were determined. Different concentrations of the saponins-rich extract were investigated for their antimicrobial potential, particularly against C. albicans, using the agar well diffusion method. To assess the potential antivirulence and antipathogenic effects, we carried out molecular docking of the bioactive saponins against four key enzymes in C. albicans, which are involved in virulence and/or pathogenicity. Different concentrations of the investigated mixture showed notable antifungal activity against C. albicans with an MIC value of 6.4 µg ml-1. Docking analysis of the investigated saponins showed their affinity toward the docked enzymes, particularly saponin 1 with secreted aspartic proteinase 3 and saponin 6 with secreted aspartic proteinase 5. Thereafter, the stability of these two protein-ligand interactions was investigated using molecular dynamics (MD) simulation. The molecular interactions between saponins and the enzymes' active sites were analyzed and discussed.

New Antiproliferative Cembrane Diterpenes from the Red Sea Sarcophyton Species.

The combination of liquid chromatography coupled to high resolution mass spectrometry (LC-HRESMS)-based dereplication and antiproliferative activity-guided fractionation was applied on the Red Sea-derived soft coral Sarcophyton sp. This approach facilitated the isolation of five new cembrane-type diterpenoids (1-5), along with two known analogs (6 and 7), as well as the identification of 19 further, known compounds. The chemical structures of the new compounds were elucidated while using comprehensive spectroscopic analyses, including one-dimensional (1D) and two-dimensional (2D) NMR and HRMS. All of the isolated cembranoids (1-7) showed moderate in vitro antiproliferative activity against a human breast cancer cell line (MCF-7), with IC50 ranging from 22.39-27.12 µg/mL. This class of compounds could thus serve as scaffold for the future design of anticancer leads.

Contribution of endophytes towards improving plant bioactive metabolites: a rescue option against red-taping of medicinal plants.

Medicinal plants remain a valuable source for natural drug bioprospecting owing to their multi-target spectrum. However, their use as raw materials for novel drug synthesis has been greatly limited by unsustainable harvesting leading to decimation of their wild populations coupled with inherent low concentrations of constituent secondary metabolites per unit mass. Thus, adding value to the medicinal plants research dynamics calls for adequate attention. In light of this, medicinal plants harbour endophytes which are believed to be contributing towards the host plant survival and bioactive metabolites through series of physiological interference. Stimulating secondary metabolite production in medicinal plants by using endophytes as plant growth regulators has been demonstrated to be one of the most effective methods for increasing metabolite syntheses. Use of endophytes as plant growth promotors could help to ensure continuous supply of medicinal plants, and mitigate issues with fear of extinction. Endophytes minimize heavy metal toxicity in medicinal plants. It has been hypothesized that when medicinal plants are exposed to harsh conditions, associated endophytes are the primary signalling channels that induce defensive reactions. Endophytes go through different biochemical processes which lead to activation of defence mechanisms in the host plants. Thus, through signal transduction pathways, endophytic microorganisms influence genes involved in the generation of secondary metabolites by plant cells. Additionally, elucidating the role of gene clusters in production of secondary metabolites could expose factors associated with low secondary metabolites by medicinal plants. Promising endophyte strains can be manipulated for enhanced production of metabolites, hence, better probability of novel bioactive metabolites through strain improvement, mutagenesis, co-cultivation, and media adjustment.

Antibacterial, Antifungal, and Anticancer Effects of Camel Milk Exosomes: An In Vitro Study.

Camel milk (CM) has potent antibacterial and antifungal effects and camel milk exosomes (CM-EXO) have been shown to inhibit the proliferation of a large variety of cancer cells including HepaRG, MCF7, Hl60, and PANC1. However, little is known regarding the effects of CM-EXO on bacteria, fungi, HepG2, CaCo2, and Vero cells. Therefore, this study aimed to evaluate the antibacterial, antifungal, and anticancer effects of CM-EXO. EXOs were isolated from CM by ultracentrifugation and characterized by transmission electron microscope and flow cytometry. Unlike CM, CM-EXO (6 mg/mL) had no bactericidal effects on Gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus, and Enterococcus feacalis) but they had bacteriostatic effects, especially against Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis), and fungistatic effects on Candida albicans. HepG2, CaCo2, and Vero cells were respectively treated with CM-EXOs at low (6.17, 3.60, 75.35 µg/mL), moderate (12.34, 7.20, 150.70 µg/mL), and high (24.68, 14.40, 301.40 µg/mL) doses and the results revealed that CM-EXOs triggered apoptosis in HepG2 and CaCo2 cells, but not in normal Vero cells, as revealed by high Bax expression and caspase 3 activities and lower expression of Bcl2. Interestingly, CM-EXOs also induced the elevation of intracellular reactive oxygen species and downregulated the expression of antioxidant-related genes (NrF2 and HO-1) in cancer cells but not in normal cells. CM-EXOs have antibacterial and antifungal effects as well as a selective anticancer effect against HepG2 and CaCo2 cells with a higher safety margin on normal cells.

Anti-cancer and antimicrobial potential of five soil Streptomycetes: a metabolomics-based study.

Lack of new anti-cancer and anti-infective agents directed the pharmaceutical research to natural products' discovery especially from actinomycetes as one of the major sources of bioactive compounds. Metabolomics- and dereplication-guided approach has been used successfully in chemical profiling of bioactive actinomycetes. We aimed to study the metabolomic profile of five bioactive actinomycetes to investigate the interesting metabolites responsible for their antimicrobial and anti-cancer activities. Three actinomycetes, namely, Streptomyces sp. SH8, SH10 and SH13, were found to exhibit broad spectrum of antimicrobial activities, whereas isolate SH4 showed the broadest antimicrobial activity against all tested strains. In addition, isolates SH8, SH10 and SH12 displayed potent cytotoxicity against the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), whereas isolates SH4 and SH12 exhibited potent anti-cancer activity against the hepatoma cell line hepatoma G2 (HepG2) compared with their weak inhibitory properties on the normal breast cells MCF-10A and normal liver cells transformed human liver epithelial-2 (THLE2), respectively. All bioactive isolates were molecularly identified as Streptomyces sp. via 16S rRNA gene sequencing. Our actinobacterial dereplication analysis revealed putative identification of several bioactive metabolites including tetracycline, oxytetracycline and a macrolide antibiotic, novamethymycin. Together, chemical profiling of bioactive Streptomycetes via dereplication and metabolomics helped in assigning their unique metabolites and predicting the bioactive compounds instigating their diverse bioactivities.

Ameliorative Effects of Camel Milk and Its Exosomes on Diabetic Nephropathy in Rats.

Contradictory results were obtained regarding the effects of extracellular vesicles such as exosomes (EXOs) on diabetes and diabetic nephropathy (DN). Some studies showed that EXOs, including milk EXOs, were involved in the pathogenesis of DN, whereas other studies revealed ameliorative effects. Compared to other animals, camel milk had unique components that lower blood glucose levels. However, little is known regarding the effect of camel milk and its EXOs on DN. Thus, the present study was conducted to evaluate this effect on a rat model of DN induced by streptozotocin. Treatment with camel milk and/or its EXOs ameliorated DN as evidenced by (1) reduced levels of kidney function parameters (urea, creatinine, retinol-binding protein (RBP), and urinary proteins), (2) restored redox balance (decreased lipid peroxide malondialdehyde (MDA) and increased the activity of antioxidants enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), (3) downregulated expression of DN-related genes (transforming growth factor-beta 1 (TGFß1), intercellular adhesion molecules 1 (ICAM1), and transformation specific 1 (ETS1), integrin subunit beta 2 (ITGß2), tissue inhibitors of matrix metalloproteinase 2 (TIMP2), and kidney injury molecule-1 (KIM1)), and (4) decreased renal damage histological score. These results concluded that the treatment with camel milk and/or its EXOs could ameliorate DN with a better effect for the combined therapy.

Effect of Different TiO2 Morphologies on the Activity of Immobilized Lipase for Biodiesel Production.

Lipase catalytic activity is greatly influenced by immobilization on nanoparticles. In this study, lipase from Aspergillus niger was immobilized on TiO2 nanoparticles with different morphologies: microspheres, nanotubes, and nanosheets. All TiO2 samples were prepared by a hydrothermal method. Lipase/TiO2 nanocomposites were prepared by a physical adsorption method through hydrophobic interactions. The prepared composites were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HRTEM). The catalytic activity of free and immobilized lipases was tested using sunflower oil in the presence of methanol to produce biodiesel at 40 °C for 90 min. The lipase immobilized on TiO2 microspheres showed the highest activity compared to the lipase immobilized on TiO2 nanotubes and nanosheets. To optimize the lipase-to-microsphere ratio, lipase was immobilized on TiO2 microspheres in different microspheres/lipase, w/w, (S/L) ratios of 1:1, 1:0.75, 1:0.5, and 1:0.25. It was noticed that the hydrolytic activity follows the order 1:0.25 > 1:0.5 > 1:75 > 1:1. The immobilization yield activities were found to be 113, 123, 125, and 130% for the microspheres/lipase (S/L) ratios of 1:1, 1:0.75, 1:0.5, and 1:0.25, respectively.

Enhancement of microbial lipase activity via immobilization over sodium titanate nanotubes for fatty acid methyl esters production.

For cost effective fatty acid methyl esters (FAME) production, nanoparticles are used to make microbial lipase more stable and reusable. Sodium titanate nanotubes (TNT) were prepared by simple hydrothermal method for immobilization of different concentrations of lipase. All samples were characterized by XRD, FTIR and HRTEM. Samples of different concentrations of immobilized lipase on titanate nanotubes (TNT-L) were tested for FAME production against free lipase & pure TNT at 40 °C for 90 min. It was found that TNT-L achieved high conversion percentages even at low immobilized lipase concentrations, compared to free lipase. Immobilized lipase on TNT demonstrated enhanced recycling stability for 10 consecutive cycles, suggesting its use for FAME production.

In vivo anti-inflammatory activity and UPLC-MS/MS profiling of the peels and pulps of Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus.

ETHNOPHARMACOLOGICAL RELEVANCE: Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus are the most famous varieties of netted muskmelon or cantaloupe in Egypt. Cantaloupe has a great reputation as an anti-inflammatory drug for hot inflammation of liver, cough, eczema, and kidney disorders such as ulcers in the urinary tract, and our objective was to confirm this use scientifically. MATERIALS AND METHODS: Inflammation was induced in adult male Sprague Dawley rats by subcutaneous injection of 0.05 ml of carrageenan (1% solution in saline) into the plantar surface of the right hind paw 30 min after oral pretreatment of the rats with 95% ethanolic extracts of Cucumis melo var. cantalupensis peels (CCP) and pulps (CCU) and Cucumis melo var. reticulatus peels (CRP) and pulps (CRU) at doses of 25 and 50 mg/kg. Indomethacin (10 mg/kg) was used as a standard drug. The effect of the tested samples was measured on the oedema volume, as well as PGE-2, TNF-α, IL-6 and IL-1ß levels. Metabolic profiling of the extracts was performed using UPLC-MS/MS analysis. RESULTS: Pretreatment of rats with the ethanol extract of the pulps and peels of the two varieties at doses of 25 and 50 mg/kg significantly inhibited the carrageenan-induced increase in the oedema volume of the rat paws after 3 h, except for the low dose of the French cantaloupe pulp. CRP at 50 mg/kg caused the most significant reductions in both TNF-α (P < 0.05) and IL-1ß (P < 0.001) levels, while CCP caused the most significant reductions in PGE-2 and IL-6 (P < 0.05) levels. Increases in PGE-2, TNF-α, IL-6 and IL-1ß levels were also significantly prevented by indomethacin (10 mg/kg). UPLC-MS/MS facilitated the identification of 44 phenolic compounds, including phenolic acids and flavonoids. CONCLUSION: This is the first report of the chemical and biological study of the peels of Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus.