Insight into antioxidant and anti-inflammatory effects of marine bacterial natural exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats.

Inflammation is a part of the body's intricate biological reaction to noxious stimuli and defensive reactions. So, the aim of this investigation was to study the anti-inflammatory activity of exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats. A halophilic bacterial strain was isolated from marine sediments in the Red Sea in Egypt. The isolate has been visually and physiologically recognized, as well as by analyzing its 16S rRNA gene, which confirms Kocuria sp. clone Asker4. This particular isolate can be referenced using the accession number OL798051.1. EPSSM was subjected to purification and fractionation by a DEAE-cellulose column. Preliminary chemical analysis of EPSSM indicated that the monosaccharides were fructose, glucuronic acid, and xylose, with 2.0, 0.5, and 1.0, respectively. The antioxidant potential of EPSSM was investigated, and it was discovered that the level of activity increased independently of the concentrations, reaching a maximum threshold of 94.13% at 100 µg/mL of EPSSM for 120 min. Also, EPSSM at 50 mg/kg orally produced a significant anti-inflammatory effect on the carrageenan model at 2, 3, and 4 intervals. The EPSSM intervention resulted in reductions in the levels of catalase and superoxide dismutase enzymes, as well as a decrease in glutathione. Furthermore, the levels of nitric oxide, lipid peroxidation, and reactive oxygen species resulting from carrageenan-induced edema showed a significant reduction subsequent to the administration of EPSSM. Moreover, the findings indicated that the protein expression levels of cyclooxygenase-2 and interleukin-6 were reduced following treatment with EPSSM, resulting in a reduction of paw edema.

Structural, dielectric, and antimicrobial evaluation of PMMA/CeO2 for optoelectronic devices.

In the current report, we have successfully synthesized nanocomposites of PMMA incorporating different doping of CeO2 through a chemical approach. XRD results reflects decent matching for CeO2 nanoparticles with 29 nm crystallite size. FTIR spectroscopy demonstrates the characteristic functional groups validating the successful formation of the composite. The optical study of PMMA and the nanocomposites has proven that the optical properties such as band gap, refractive index, optical permittivity, and loss tangent factor are affected by adding CeO2 to the PMMA matrix.The peak residing around 420 nm by UV measurements is allocated to occurring electrons photoexcitation from the valence to conduction band inherent in CeO2. The dielectric measurements were achieved using broadband dielectric spectroscopy upon a wide span of frequencies (10-1-107 Hz) and within temperatures from - 10 to 80 °C with a step of 10 °C. The permittivity decreases by adding CeO2 and the dielectric parameters are thermally enhanced, however, the temperature influence is based on CeO2 content, the higher the CeO2 amount, the higher the influence of temperature. The results of the nanocomposites revealed antibacterial activity counter to gram-positive bacteria strain (S. aureus, and B. subtilis), and gram-negative bacteria (E. coli, and K. pneumoniae), yeast (C. albicans, as well as fungi (A. niger). Inherently, the change in CeO2 concentration from 0.01 to 0.1 wt% delivers maximum influence against gram-negative bacteria. These PMMA CeO2-doped composites are beneficial for optoelectronic areas and devices.

Characterization and in-vitro Alzheimer's properties of exopolysaccharide from Bacillus maritimus MSM1.

Four bacterial isolates were obtained from marine sediments collected from Sahl Hashish, Hurghada Red Sea, Egypt. This study was designed to search for promising anti-Alzheimer natural polysaccharide; therefore, four isolates were screened for exopolysaccharides (EPSs) production and acetylcholinesterase inhibition. The isolate S16 provided the highest EPS yield (7.51 g/L) and acetylcholinesterase inhibition. It was identified morphologically and genetically using 16S rRNA gene sequence analysis as Bacillus maritimus. A Physicochemical analysis of S16 exopolysaccharide (BMEPS) was estimated, which pointed to the presence of uronic acid and sulfate (24.7% and 18.3%, respectively). HPLC analysis indicated that mannuronic acid, glucuronic acid, glucose, and mannose are presented in a molar ratio of 0.8:1.0:2.8:2.3, respectively. Furthermore, FT-IR revealed an abundance of ß-configurations. The GPC estimated the average molecular weight (Mw) as 4.31 × 104 g/mol. BMEPS inhibited AChE (IC50; 691.77 ± 8.65 µg/ ml), BChE (IC50; 288.27 ± 10.50 µg/ ml), and tyrosinase (IC50; 3.34 ± 0.09, 14.00 ± 0.14, and 22.96 ± 1.23 µg/ ml during incubation durations of 10, 20, and 40 min). It also demonstrated a selective anti-inflammatory action against COX-2 rather than COX-1. Moreover, BMEPS exhibited antioxidant capabilities as free radical and oxygen reactive species (ROS) scavenger, metal chelator, reductant agent, and lipid peroxidation suppressor. These activities are due to the distinct chemical composition. The findings of this study indicate that BMEPS could be considered as promising anti-disease Alzheimer's (AD) material in an in-vitro model, which qualifies it for advanced in-vivo studies in the discovery of alternative Alzheimer's treatment.

Study of exopolysaccharide produced by Streptomyces rochie strain OF1 and its effect as ameliorative on osteoarthritis in rats via inhibiting TNF-α/COX2 pathway.

BACKGROUND: Carbohydrates are known as the main natural products of life activities. RESULTS: Streptomyces rochie strain OF1 isolated from a mangrove tree produced exopolysaccharide S5 (EPSS5) (14.2 gl-1) containing uronic acid 21.98% sulfate content of 11.65 mg/ml, and a viscosity of 1.35 mm2/s. while total hexose amine content was 24.72%. The high performance liquid chromatography (HPLC) analysis of mono sugars revealed that EPS was composed of manouronic acid, glucuronic acid, xylose, and fructose at a molar ratio of 1.0:0.5:1.0:2.0, respectively. It showed that the whole antioxidant activity was 92.06%. It showed antibacterial activity against Staphylococcus aureus, and E. coli, MRSA and Klebsiella pneumoniae. But, EPSS5 displayed low antifungal activity against Candida albicans. While no antifungal activity has been detected against Aspergillus niger. EPSS5 has antibiofilm action that is noticeable toward S. aureus with an inhibition ratio of biofilm up to 50%. Effect of EPS on serum levels of TNF-α and COX2 by 2 fold and 1.9 fold of EPS reduced serum levels of Tumor necrosis factor-α (TNF-α) by 38%, 12%, 49%, and Cyclooxygenase-2 (COX2) by 61%, 34%, and 62%, respectively. By affected of EPSS5 on arthritis in rats stimulated by carrageenan. CONCLUSIONS: Administration of EPS ameliorated carrageen-induced elevation in inflammatory mediators; TNF-α/COX and suppressed the expressions of metalloproteinase 9 (MMP9) by 68%, 86%, and 75% correspondingly in comparison to the group of carrageenans. Then again, therapy involving a high dose only reduced MMP9 level by 57%, compared to free drug suggesting that EPSS5 is a good inhibitor of the MMP9, as it brought MMP9 back to normal levels via the signaling pathway.

Synthesis, Molecular Docking and Biological Evaluation of Novel Flavone Derivatives as Potential Anticancer Agents Targeting Akt.

BACKGROUND: Flavonoids are naturally occurring compounds with versatile healthpromoting effects against various diseases. OBJECTIVE: This aim of this paper is to synthesize and evaluate the biological activity of novel flavone derivatives against cancer. METHODS: A new series of 2-hydroxy-α,ß-unsaturated ketones 2a-h, was synthesized via the reaction of N-substituted-indole-3-carboxaldehyde 1a-h with 2-hydroxy acetophenone in the presence of piperidine. The oxidative cyclization of 2a-h using hydrogen peroxide/KOH and/or dimethyl sulfoxide/I2 produced the corresponding 2-(N-substituted-1H-indol-3-yl)-3-hydroxy-4H-chromen- 4-ones 3a-h and 2-(N-substituted-1H-indol-3-yl)-4H-chromen-4-ones 4a-h, respectively. Antiproliferative activities for synthesized series were investigated against HCT-116 colon and MCF- 7 breast cancer cell lines. Molecular downstream effects were evaluated using RT-PCR. Moreover, molecular docking was carried out to pinpoint the binding mode of the most active compounds into the active site of Akt enzyme (PDB ID: 3QKK). RESULTS: All compounds exhibited an anti-proliferative activity range of 52-97% and 67.2-99% against HCT-116 and MCF-7, respectively. Compounds 3b, 3h, 3g and 4h had a minimal inhibitory effect on normal BJ1 cells indicating their safety profile. Compounds 3b and 4h, in particular, exhibited the most potent antiproliferative activity against HCT116 and MCF7, meanwhile compounds 3g, 3h and 4g showed potent to moderate activity. Compound 3b had IC50 of 78.3 µM and 53.9 µM against HCT-116 and MCF-7 respectively with comparable IC50 for doxorubicin of 65.1 µM and 45.02 µM. Compound 3b exhibited significant down-regulation for Akt and significant up-regulation of CAS9 and CDKN1genes in all tested cell lines. CONCLUSION: The synthesized flavone derivatives and particularly compound 3b exhibited promising anticancer activity through Akt inhibition.

Diverse bioactive metabolites from Penicillium sp. MMA derived from the red sea: structure identification and biological activity studies.

A soft coral-derived fungus Penicillium sp. among other isolates e high antibacterial, anti-yeast and cytotoxic activities. The fungus, Penicillium sp. MMA, isolated from Sarcphyton glaucoma, afforded nine diverse compounds (1-9). Their structures were identified by 1D and 2 D NMR and ESI-MS spectroscopic data as two alkaloids: veridicatol (1), aurantiomide C (2); one sesquiterpene, aspterric acid (3); two carboxylic acids, 3,4-dihydroxy-benzoic acid; (4) and linoleic acid (5); three steroids, ergosterol (6), ß-Sitosterol (7), ß-Sitosterol glucoside (8) along with the sphingolipid, cerebroside A (9). Biologically, the antimicrobial, antioxidant, in vitro cytotoxicity and antibiofilm activities were studied in comparison with the fungal extract. The in silico computational studies were implemented to predict drug and lead likeness properties for 1-4. The fungus was taxonomically characterized by morphological and molecular biology (18srRNA) approaches.

Exopolysaccharide from Marine Bacillus velezensis MHM3 Induces Apoptosis of Human Breast Cancer MCF-7 Cells through a Mitochondrial Pathway

Objective: The production of new natural pharmaceutical agents that increase the efficiency of chemotherapy without affecting the normal cells is the goal of all researchers. Therefore, the present study expects to evaluate the antioxidant and anticancer studies against MCF-7 cell lines of EPS produced by novel Egyptian marine bacterial strain. Methods: Marine bacterium was isolated, purified and identified by 16S rRNA gene amplification and sequence analyses. MHMEPS (the produced EPS) was analyzed by Fourier Transform Infra-red (FTIR), monosugars identification by HPLC, molecular weight estimation and sulfur content were determined. While, in-vitro antioxidants characters was determined using various methods and anticancer studies against MCF-7 cell lines. Results: Bacillus velezensis MHM3 produced 5.8 g/L of MHMEPS. The chemical analysis of MHMEPS showed 24% uronic acid and 18.19% sulfate and monosugars glucuronic acid, glucose, fructose and rhamnose with molar ratio of 4.00: 2.00: 1.00: 0.13, correspondingly, with an overall weight average molecular weight Mw of 1.145×104 g/mol and the number average of molecular weights Mn of 5.155 ×103 g/mol. The FTIR analysis and periodate oxidation indicate the existence of ß-(1­4) linkage acidic polysaccharide. MHMEPS showed antioxidant scavenging activity against DPPH•, H2O2 and Metal chelating activity, respectively. So, reducing power method give high activity at 500 µg/ml. MHMEPS hinder the proliferation of MCF-7 cells at 5-80 µg/ml compared to the control group. Moreover, induced apoptosis was associated with activation of caspase-3. Also increased cytochrome C levels significantly in a dose-dependent manner compared with the control. The Caspase-3 activity was raised in MHMEPS treated MCF-7 cells compared with the control (p<0.05) in a dose-dependent manner. Therefore, the result of DNA fragmentation was confirmed by DNA ladder assay. We presume that MHMEPS has high potential at its low concentration, as a novel restorative agent for the treatment of MCF-7 cells, with no cytotoxicity against normal cells.

Production, characterization and biological activities of acidic exopolysaccharide from marine Bacillus amyloliquefaciens 3MS 2017.

OBJECTIVE: To evaluate in-vitro antioxidant, anti-inflammatory and antitumor abilities against human breast adenocarcinoma (MCF7) and human prostate cancer (PC3) as well as the suppressor effect of bacterial exopolysaccharide (BAEPS) on Ehrlich ascites carcinoma (EAC). METHODS: In-vitro antioxidants characters of BAEPS were determined using various methods, while anti-inflammatory activity was estimated against cyclooxygenase (COX-1 and COX-2). In-vitro study, anticancer against MCF7 and PC3 were assessed by the mitochondrial dependent reduction of yellow MTT. In in-vivo study against EAC progression, mice were inoculated with EAC cells and then were orally administered BAEPS at 200 mg/kg after 24 h (equals to 0.10 of determined LD50)/10 d. RESULTS: BAEPS was acidic exopolysaccharide contained uronic acid (12.3%) and sulfate (22.8%) with constitution of glucose, galactose and glucuronic acid in a molar ratio 1.6:1.0:0.9, respectively, with a molecular mass of 3.76 × 104 g/mol. BAEPS appeared potent antioxidant characters as free radical scavenging, oxygen reactive species scavenging and metal chelation, while its reducing power was low. BAEPS showed selective anti-inflammatory activity against COX-2 than COX-1, COX-2 selective. BAEPS exhibited potent and selective effect to breast cell cancer MCF7, the death percentage was 65.20% with IC50 = 70 µg/mL and IC90 = 127.40 µg/mL. BAEPS decreased counted viable EAC cells and induced non-viable cells. BAEPS improved all assessed hematological parameters. These improvements were reflected in the increasing median survival time and significant increment (P < 0.05) in life span. CONCLUSIONS: BAEPS has anti-tumor activity with a good margin of safety. The anti-tumor activity of BAEPS may be due to its content from sulfated groups and uronic acids and they have antioxidant and anti-inflammatory properties.

Production of hydroxy marilone C as a bioactive compound fromStreptomyces badius.

Hydroxy marilone C is a bioactive metabolite produced from the culture broth of Streptomyces badius isolated from Egyptian soil. Hydroxy marilone C was purified and fractionated by a silica gel column with a gradient mobile phase dichloromethane (DCM):methanol then Sephadex LH-20 column using methanol as a mobile phase. It was subjected to many procedures such as infrared (IR), nuclear magnetic resonance (NMR), Mass spectroscopy (MS) and UV spectroscopy for elucidation of its structure. It was evaluated for antioxidant, cytotoxicity against human alveolar basal epithelial cell line (A-549) and human breast adenocarcinoma cell line (MCF-7) and antiviral activities; showed that the maximum antioxidant activity was 78.8% at 3 mg/ml after 90 min. and the IC50 value against DPPH radical found about 1.5 mg/ml after 60 min. Using MTT assay the effect of the pure compound on the proliferation of A-549 cells and MCF-7 cells was 443 µg/ml and 147.9 µg/ml, respectively, while for detection of antiviral activity using Madin-Darby canine kidney (MDCK) cells the maximum cytotoxicity was at 27.9% and IC50 was 128.1 µg/ml. The maximum concentration required for protecting 50% of the virus-infected cells against H1N1 viral cytopathogenicity (EC50) was 33.25% for 80 µg/ml. These results indicated that the hydroxy marilone C has potential antitumor and antiviral activities.