The burden of antibiotic resistance necessitates a continued search for new antimicrobials. We evaluated the antimicrobial activities of novel benzothiazoles synthesized by our group. Antibacterial activity was evaluated in vitro in Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, while the antifungal activity was tested in Candida albicans and Aspergillus niger, and expressed as the minimum inhibitory concentration (MIC; µg/mL). MIC values of benzothiazole compounds ranged from 25 to 200 µg/mL. Compounds 3 and 4 gave high antibacterial and moderate antifungal activities, while 10 and 12 showed moderate activity against all tested organisms. In addition, some benzothiazole compounds significantly suppressed the activity of Escherichia coli dihydroorotase and inhibited the dimorphic transition of Candida albicans. Moreover, the active benzothiazole compounds induced DNA and protein leakage in Aspergillus niger spores. Molecular interactions of benzothiazole derivatives with dihydroorotase revealed the formation of hydrogen bonds with the active site residues LEU222 or ASN44. Strong hydrophobic interactions of the bulky thiazole and naphthalene rings at the entrance to the active site might interfere with the access of substrates to their binding sites, which results in dihydroorotase inhibition. Thus, inhibition of dihydroorotase might contribute to the observed antimicrobial actions of these compounds.

Stroke is one of the main causes of mortality and disability, and it is due to be included in monetary implications on wellbeing frameworks around the world. Ischemic stroke is caused by interference in cerebral blood flow, leading to a deficit in the supply of oxygen to the affected region. It accounts for nearly 80–85% of all cases of stroke. Oxidative stress has a significant impact on the pathophysiologic cascade in brain damage leading to stroke. In the acute phase, oxidative stress mediates severe toxicity, and it initiates and contributes to late-stage apoptosis and inflammation. Oxidative stress conditions occur when the antioxidant defense in the body is unable to counteract the production and aggregation of reactive oxygen species (ROS). The previous literature has shown that phytochemicals and other natural products not only scavenge oxygen free radicals but also improve the expressions of cellular antioxidant enzymes and molecules. Consequently, these products protect against ROS-mediated cellular injury. This review aims to give an overview of the most relevant data reported in the literature on polyphenolic compounds, namely, gallic acid, resveratrol, quercetin, kaempferol, mangiferin, epigallocatechin, and pinocembrin, in terms of their antioxidant effects and potential protective activity against ischemic stroke.

The approaches used for the green biosynthesis of nanoparticles with clinical applications have been widely used in nanotechnology due to their potential to provide safe, eco-friendly, cost effective, high-stability, and high-loading-capacity nanoparticles. This study aimed to evaluate the anti-candidal activity of silver nanoparticles (AgNPs) biosynthesized using the aqueous leaf extract of Calotropis gigantea (CG) alone or in a combination with the plant extract of CG (AgNPs/CG). AgNPs were characterized using UV-Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The results of the standard disk diffusion method revealed that AgNPs alone displayed anti-candidal activity (11.33-mm inhibition zone), while AgNPs/CG displayed a strong synergistic anti-candidal activity (17.76-mm inhibition zone). Similarly, AgNPs/CG completely inhibited the growth of C. albicans after 4 h of incubation, as measured using the time-kill assay. In addition, AgNPs/CG inhibited the dimorphic transition of C. albicans and suppressed both the adhesion and the biofilm formation of C. albicans by 41% and 38%, respectively. The treatment of Candida. albicans with AgNPs/CG showed a significant inhibition of the production of several antioxidant enzymes. Interestingly, AgNPs/CG did not show any cytotoxicity in animal cells, including the MCF-7 cell line and primary mouse bone marrow-derived mesenchymal stem cells (mBMSCs), at the concentration used to completely inhibit the dimorphic transition of C. albicans. In conclusion, we identified AgNPs/CG as a promising natural-product-based nanoparticle that can potentially be used as an anti-candidal drug.

Oral candidiasis (OC) is a fungal infection caused by an opportunistic fungi Candida albicans, which is found in the normal flora of healthy people. In this study, we examined the anti-candidal effect of green synthesized silver nanoparticles using leaf extract of Erodium glaucophyllum (EG-AgNPs) against C. albicans in vitro and in vivo. EG-AgNPs were synthesized for the first time using E. glaucophyllum extract and characterized by imaging (transmission electron microscopy (TEM), UV-VIS spectroscopy, zeta potential, X-ray diffraction (XRD), Energy dispersive x-ray analysis (EDX), and Fourier transform infrared spectroscopy (FTIR). A mouse model of OC was used for in vivo study. The agar well diffusion method showed the anti-candidal activity of EG-AgNPs against C. albicans with MIC 50 µg/mL. EG-AgNPs inhibited the dimorphic transition of C. albicans and suppressed the formation of biofilm by 56.36% and 52%, respectively. Additionally, EG-AgNPs significantly inhibited the production of phospholipases and proteinases by 30% and 45%, respectively. EG-AgNPs cause cytoplasm disintegration and deterioration of cell wall as imaged by SEM and TEM. Interestingly, EG-AgNPs did not display any cytotoxicity on the human gingival fibroblast-1 HGF-1 cell line at MIC concentrations. Topical treatment of the tongue of the OC mouse model with EG-AgNPs showed significant reduction in candidal tissue invasion, less inflammatory changes, and no tissue modification, in association with marked low scare and hyphal counts as compared to control group. In conclusion, our data demonstrated the potent inhibitory action of EG-AgNPs on the growth and morphogenesis of C. albicans in vitro and in vivo. Thus, EG-AgNPs represent a novel plausible therapeutic approach for treatment of OC.

Identifying bone anabolic agents is a superior strategy for the treatment of osteoporosis. Naturally, derived coumarin derivatives have shown osteoanabolic effect in vitro and in vivo. In this study, we investigated the effect of 5′-Hydroxy Auraptene (5′-HA), a coumarin derivative that newly isolated from Lotus lalambensis Schweinf on the differentiation of the mouse bone marrow-derived mesenchymal (skeletal) stem cells (mBMSCs) into osteoblast and adipocyte. The effect of 5′-HA on mBMSCs cell proliferation and osteoblast differentiation was assessed by measuring cell viability, quantitative alkaline phosphatase (ALP) activity assay, Alizarin red staining for matrix mineralization and osteogenic gene array expression. Adipogenesis was measured by Oil Red O staining and quantitative real time PCR (qPCR) analysis of adipogenic markers. Regulation of BMPs signaling pathways by 5′-HA was measured by Western blot analysis and qPCR. 5′-HA showed to stimulate the differentiation of mBMSCs into osteogenic cell lineage in a dose-dependent manner, without affecting their differentiation into adipocytic cell lineage. Treatment of mBMSCs with 5′-HA showed to promote significantly the BMP2-induced osteogenesis in mBMSCs via activating Smad1/5/8 phosphorylation and increasing Smad4 expression. Blocking of BMP signaling using BMPR1 selective inhibitor LDN-193189 significantly inhibited the stimulatory effect of 5′-HA on osteogenesis. Our data identified 5′-HA, as a novel coumarin derivative that function to stimulate the differentiation of mBMSCs into osteoblasts in BMP-signaling dependent mechanism.

The present study was undertaken to investigate the antifungal, antiaflatoxigenic, antioxidant, and anticancer activities of Glycyrrhiza glabra L. and Matricaria chamomilla L.essential oils and their phytochemical composition. The essential oils were obtained by hydrodistillation and their phytochemical composition was determined throughout gas chromatography-mas spectrometry (GC-MS) analysis. Both essential oils and their mixture showed broad antifungal spectrum against Aspergillus flavus, an important food contaminating fungus. The essential oils of G. glabra and M. chamomilla completely inhibited aflatoxin B1 (AFB1) production at 800 ppm. Both oils exhibited antioxidant activity as DPPH free radical scavenger in dose dependent manner. Percentage of radical scavenging activity of G. glabra and M. chamomilla oils at 400 μg/ml were calculated to be 85.2 and 91.7%, respectively as compared to standard (BHT) with 75.6% activity at the same concentration. The anticancer properties of essential oils against cells (MCF-7) were evaluated. In anticancer activity exposure of essential oils caused a significant decrease in cell viability in MCF-7 cell line (breast carcinoma). Exposure of MCF-7 cells with G. glabraessential oils resulted in dose dependent increase in cell growth inhibition (CGI) varying from 3 to 77% at concentration ranging from 10 to 640 μg/ml. Similarly, 7 to 89% CGI was obtained when M. chamomilla essential oils was used. The present study demonstrated that essential oils of G. glabra and M. chamomilla have potent antifungal, antioxidant, and anticancer with the presence of effective phytochemicals. Key words: Glycyrrhiza glabra, Matricaria chamomilla, essential oil, antifungal, antiaflatoxigenic, antioxidant, anticancer.