Unveiling the role of gut dysbiosis in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial complicated condition, reflected by the accumulation of extra fat in the liver. A detailed study of literature throws light on the fascinating connection between gut dysbiosis and NAFLD. The term 'gut dysbiosis' describes an imbalance in the harmony and operation of the gut microflora, which can upshoot a number of metabolic disorders. To recognize the underlying mechanisms and determine treatment options, it is essential to comprehend the connection between gut dysbiosis and NAFLD. This in-depth review discusses the normal gut microflora composition and its role in health, alterations in the gut microflora composition that leads to disease state focusing on NAFLD. The potential mechanisms influencing the advent and aggravation of NAFLD suggested disturbance of microbial metabolites, changes in gut barrier integrity, and imbalances in the composition of the gut microflora. Furthermore, it was discovered that gut dysbiosis affected immune responses, liver inflammation, and metabolic pathways, aggravating NAFLD.

Data on docking of phytoconstituents of Actinidia deliciosa on dengue viral targets.

Major Phytoconstituents of Actinidia deliciosa were explored for their anti-viral potential against dengue virus (DENV). The docking of these phytoconstituents was performed on 7 viral targets- 4 DENV non structural protein (NS5-SAM binding domain, NS5 RdRp domain, NS3 helicase & NS2B-NS3 protease) and 3 DENV structural proteins (Envelope protein-ß-OD domain, stem domain & Domain III). The analysis was done on the basis of binding affinity, type of interactions (bond type and distance) and interaction with amino acids significant in viral replication. The top 5 phytoconstituents with best docking score have been reported.

Computational data of phytoconstituents from Hibiscus rosa-sinensis on various anti-obesity targets.

Molecular docking analysis of twenty two phytoconstituents from Hibiscus rosa-sinensis, against seven targets of obesity like pancreatic lipase, fat and obesity protein (FTO protein), cannabinoid receptor, hormones as ghrelin, leptin and protein as SCH1 and MCH1 is detailed in this data article. Chemical structures of phytoconstituents were downloaded from PubChem and protein structures were retrieved from RCSB protein databank. Docking was performed using FlexX software Lead IT version 2.3.2; Bio Solved IT. Visualization and analysis was done by Schrodinger maestro software. The docking score and interactions with important amino acids were analyzed and compared with marketed drug, orlistat. The findings suggest exploitation of best ligands experimentally to develop novel anti-obesity agent.

Nitrogen Mustards as Alkylating Agents: A Review on Chemistry, Mechanism of Action and Current USFDA Status of Drugs.

BACKGROUND & OBJECTIVE: Nitrogen mustard derivatives form one of the major classes of anti-cancer agents in USFDA approved drugs list. These are polyfunctional alkylating agents which are distinguished by a unique mechanism of adduct formation with DNA involving cross-linking between guanine N-7 of one strand of DNA with the other. The generated cross-linking is irreversible and leads to cell apoptosis. Hence it is of great interest to explore this class of anticancer alkylating agents. METHODS: An exhaustive list of reviews, research articles, patents, books, patient information leaflets, and orange book is presented and the contents related to nitrogen mustard anti-cancer agents have been reviewed. Attempts are made to present synthesis schemes in a simplified manner. The mechanism of action of the drugs and their side effects are also systematically elaborated. RESULTS: This review provides a platform for understanding all aspects of such drugs right from synthesis to their mechanism of action and side effects, and lists USFDA approved ANDA players among alkylating anticancer agents in the current market. CONCLUSION: Perusing this article, generic scientists will be able to access literature information in this domain easily to gain insight into the nitrogen mustard alkylating agents for further ANDA development. It will help the scientific and research community to continue their pursuit for the design of newer and novel heterocyclic alkylating agents of this class in the coming future.

Synthesis and Biological Evaluation of Novel 2-(4-acetyl-3-methyl- 5-(arylamino) thiophen-2-yl)-3-arylquinazolin-4(3H)-one Derivatives as Potential Anti-inflammatory and Antioxidant Agents.

BACKGROUND: A new series of 2-(4-acetyl-3-methyl-5-(arylamino) thiophen-2- yl)-3-arylquinazolin-4(3H)-one derivatives (11a-11j) were synthesized from acetyl acetone, phenyl isothiocyanate and 2-chloromethyl quinazolinone. OBJECTIVE: Due to side effects of Non Steroidal Anti-Inflammatory Drugs (NSAID), an attempt was made to identify the novel tetrasubstituted thiophene lead compound as potential anti-inflammatory and antioxidant agent. METHODS: Then newly synthesized compounds were characterized by IR spectroscopy, 1H NMR and mass spectrometry. The synthesized compounds were screened for their in vivo anti-inflammatory activity in carrageenan-induced rat hind paw edema model at dose 20mg/kg body weight using diclofenac sodium as a standard drug. The compounds were also evaluated for their in vitro DPPH free radical-scavenging activity and nitric oxide radical scavenging activity at the concentrations of 10, 20, 40, 60, 80 and 100 µg/mL using ascorbic acid as standard drug. RESULTS: The results from carrageenan-induced rat hind paw edema showed that compounds 11e, 11f and 11b show a significant anti-inflammatory activity of 46.61%, 48.94% and 47.04 % protection respectively to inflamed paw but less than diclofenac sodium. Compounds 11h and 11e show good DPPH free radical scavenging and nitric oxide radical scavenging activity, respectively. CONCLUSION: From results, it was observed that highly substituted thiophene scaffold exhibits anti-inflammatory and antioxidant activity.

Employing Central Composite Design for Evaluation of Biomass Production by Fusarium venenatum: In Vivo Antioxidant and Antihyperlipidemic Properties.

The present study deals with the cost effective production of biomass from Fusarium venenatum using different carbon sources (cane sugar, brown sugar, malt and fructose). Optimization of selected carbon sources and seed size using Central Composite Response Surface Design (CCRSD) indicated that sucrose (1.64 g/100 mL) and seed size (10% v/v) were optimal in maximizing biomass yield (0.5602 g/100 mL, p < 0.0001) and protein yield (49.99%, p < 0.01) of Fusarium venenatum. The acetonitrile and methanolic extracts of biomass showed promising antioxidant activity (DPPH assay, 59.7 and 51.9% respectively, 250 µg/mL). The mycoprotein, in the Triton-X 100-induced hyperlipidemic model in rats, exhibited significant reduction of serum lipids levels (p < 0.01 at 100, 200 and 400 mg/kg body weight) with significant increase in HDL level. It also exhibited antibacterial activity against S. aureus. LC-MS analysis of ACN extract of biomass showed two major peaks (Compound 3: m/e 701.4941 and Compound 2: m/e 651.4984). Spectral matching with standard MS libraries indicated that compound 3 may be structurally similar to sterol glycoside (m/e 716.99) with absence of methyl group. Also, compound 2 may be cholest-5-en-3-ol (3ß)-, 9-octadecenoate. These results showed that Fusarium venenatum can act as a source of natural antioxidant along with acting as a valuable protein source. It may also prove to be beneficial in treatment of hyperlipidemia and other cardiovascular conditions. Further bioactivity-guided fractionation and isolation will help to obtain bioactives that may serve as leads for design of new class of therapeutic agents.

Microwave-assisted facile synthesis of a new tri-block chitosan conjugate with improved mucoadhesion.

A new chitosan-based tri-block conjugate, O-PEG-chitosan-N-cysteine was synthesized using microwave irradiation. For synthesis of this derivative, chitosan was modified to a PEG-chitosan conjugate followed by PEG-chitosan-cysteine using 6-O PEGylation and 2-N-thiolation, respectively. The synthesized derivative was characterized using various analytical techniques such as FT-IR and (1)H NMR spectroscopy. The conjugate was also analyzed for its biochemical, biodegradation and mucoadhesive properties. The modified chitosan conjugate exhibited improved mucoadhesion behavior (14.0 h) with greater biodegradation compared to the parent polymer (6.3h). The in silico modeling corroborated with the in vitro study demonstrating a stable complex between mucin and O-PEG-chitosan-N-cysteine conjugate (ΔE=-60.100 kcal/mol) compared to mucin and chitosan conjugate. The synthesis proposed herein, involves the use of microwave irradiation which causes a substantial reduction in the reaction time (approximately 2.30 h) compared to conventional method (35 h).

Anti-inflammatory and antiarthritic activity of anthraquinone derivatives in rodents.

Aloe emodin is isolated compound of aloe vera which is used traditionally as an anti-inflammatory agent. In vitro pharmacokinetic data suggest that glucuronosyl or sulfated forms of aloe emodin may provide some limitations in its absorption capacity. Aloe emodin was reported to have in vitro anti-inflammatory activity due to inhibition of inducible nitric oxide (iNO) and prostaglandin E2, via its action on murine macrophages. However, present work evidenced that molecular docking of aloe emodin modulates the anti-inflammatory activity, as well as expression of COX-2 (cyclooxygenase-2) in rodent. The AEC (4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2 carboxylic acid) was synthesized using aloe emodin as starting material. The study was planned for evaluation of possible anti-inflammatory and antiarthritic activity in carrageenan rat induced paw oedema and complete Freund's adjuvant induced arthritis in rats. The AE (aloe emodin) and AEC significantly (P < 0.001) reduced carrageenan induced paw edema at 50 and 75 mg/kg. Complete Freund's adjuvant induced arthritis model showed significant (P < 0.001) decrease in injected and noninjected paw volume, arthritic score. AE and AEC showed significant effect on various biochemical, antioxidant, and hematological parameters. Diclofenac sodium 10 mg/kg showed significant (P < 0.001) inhibition in inflammation and arthritis.

Effect of Woodfordia fruticosa on dexamethasone induced insulin resistance in mice

Diabetes is a group of syndrome characterized by hyperglycemia, altered metabolism of lipids, carbohydrates and proteins, resulting in an increased risk of complications from vascular disease. The flowers of Woodfordia fruticosa (L.) Kurz, Lythraceae, have been used traditionally in the treatment of diabetes, dysentery, diarrhea, other bowel complaints, internal haemorrhages, in leucorrhoea and menorrhagia. Externally powdered flower is sprinkled over foul ulcers and wounds for diminishing their discharge and promoting granulations. In Konkan leaves are used in bilious sickness. W. fruticosa is also reported to have DNA topoisomerase inhibitor, antibacterial, antifertility, antipeptic ulcer, free radical scavenging, and hepatoprotective activity. W. fruticosa is a medicinal plant used to treat a wide range of disorder including diabetes. The present work investigates the effects of the WF in dexamethsone induced insulin resistance in mice. The results of animal study revealed that the extract at dose 100, 200 and 400 mg/kg was found to be significant (p<0.01) after 22 days of treatment. Further isolation studies afforded an anthraquinone glycoside, chrysophanol-8-O-β-D-glucopyranoside. Moreover further experiments will be required to identify their exact mechanism of action.

Spectrophotometric bioassay method for urokinase.

INTRODUCTION: Urokinase is a potent plasminogen activator. Present Bio assay methods of Urokinase are very tedious. So a new simple spectrophotometric Bio assay method was developed to estimate thrombolytic activity of Urokinase. METHODS AND RESULTS: This Bio assay is designed for the quantitative in vitro spectrophotometric determination of Urokinase activity by utilizing its thrombolytic activity to carry out the lysis of plasma clots. The initial concentration of the plasma clots was adjusted to 0.2+/-0.01 absorbance and the linear decrease in the absorbance by addition of Urokinase concentration from 200 to 1200 IU/ml at lambda(max) 530 nm was studied. The activity of sample Urokinase can be quantified by comparing the absorbance of sample Urokinase with Urokinase standard Bio assay calibration curve and predicted in IU. The r(2) value of standard calibration curve was found out to be 0.993. The repeatability of the Bio assay was studied by performing the experiment six times with fresh plasma samples and the results showed significant similarity. DISCUSSION: We can conclude that the novel Bio assay method was found to be simple, economical, reproducible and accurate than the present Bio assay methods.

High-performance liquid chromatographic fingerprint for quality control of Terminalia arjuna containing Ayurvedic churna formulation.

Because Ayurvedic herbal preparations contain a myriad of compounds in complex matrixes, it is difficult to establish quality control standards for raw materials and to standardize finished Ayurvedic drugs. A novel, accurate, and valid fingerprint method was developed using HPLC for quality control of a traditional Ayurvedic Arjuna churna formulation, which is used as a cardiotonic drug. Comprehensive comparison of chromatograms of standardized formulation of Arjuna churna and marketed formulations revealed eight characteristic peaks in chromatograms, which unambiguously confirmed the presence of authentic raw material used in the formulation on the basis of their retention time values and UV data. An HPLC fingerprint was also developed for total sapogenins present in Terminalia arjuna. The six common peaks observed in chromatograms of isolated sapogenins, standardized formulations, and marketed formulations can serve as a quality control tool for qualitative estimation of total saponin glycosides present in an Arjuna churna formulation.

Purification and partial characterization of thermostable serine alkaline protease from a newly isolated Bacillus species HSRB08 from hotspring.

The purpose of the research was to study the purification and partial characterization of thermostable serine alkaline protease from a newly isolated Bacillus species HSRB08, which was isolated from hotspring. The enzyme was purified in a 2-step procedure involving ammonium sulfate precipitation and Sephadex G-200 chromatography. The enzyme was shown to have molecular weight of 66 kD by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Gelatin Zymogram and was purified 15.3-fold with a yield of 7.5%. It was most active at 45 degrees C, pH 9.0, with casein as substrate. It was strongly activated by metal ions such as Ca2+, Mg2+, and Mn2+. Enzyme activity was inhibited strongly by phenylmethyl sulphonyl fluoride (PMSF) but was not inhibited by ethylene diamine tetra acetic acid (EDTA), while a slight inhibition was observed with beta-mercaptoethanol (beta-ME). The compatibility of the enzyme was studied with commercial and local detergents in the presence of 10 mM CaCl2. The addition of 10 mM CaCl2 individually and in combination, was found to be very effective in improving the enzyme stability. This enzyme improved the cleansing power of various detergents. It removed blood stains completely when used with detergents in the presence of 10 mM CaCl2.

Media optimization studies for Serratiopeptidase production from Serratia marcescens ATCC 13880.

Production of an anti-inflammatory enzyme serratiopeptidase by fermentation with Serratia marcescens ATCC 13880 was studied to ascertain optimal nutritional conditions for large scale production. To study biosynthesis and production of serratiopeptidase by Serratia marcescens ATCC 13880, different physicochemical parameters were studied and optimized. The optimized medium contain, (g/l) glycerine 10.0, maltose 10.0 as carbon source, peptone 10.0 as organic nitrogen source, ammonium sulphate 10.0 as inorganic nitrogen source, dihydrogen phosphate 10.0, sodium bicarbonate 10.0, sodium acetate 10.0 as inorganic salt source, ascorbic acid 10.0 as stabilizer, distilled water 1000 ml and the optimized fermentation conditions were pH 7.0, temperature 37 degrees C and duration 24 hr. The modified fermentation medium produced 27.36 IU/ml of serratiopeptidase compared to 17.97 IU/ml in basal medium and the molecular weight of the purified serratiopeptidase was found to be 52 kD.

Simultaneous spectrophotometric estimation of Hydrochlorothiazide, Atenolol and Losartan potassium in tablet dosage form.

Two simple, accurate and reproducible spectrophotometric methods have been developed for the simultaneous estimation of Hydrochlorothiazide (Hctz), Atenolol (Atn) and Losartan potassium (Los) in combined tablet dosage forms. The first method involves determination using the simultaneous equation method, the sampling wavelengths selected are, 272.5 nm, 224 nm and 250 nm over the concentration ranges of 0.5-30 microg/ml, 1-50 microg/ ml and 1-60 microg/ml for Hctz, Atn and Los respectively. The second method is the First order derivative method, the sampling wavelengths selected for estimation of Hctz, Atn and Los are 280.5 nm, 233 nm and 244 nm with linearity in the concentration ranges of 0.5-30 microg/ ml, 1-50 microg/ml and 1-60 microg/ml respectively. The results of the analysis were validated statistically and recovery studies were carried out as per ICH guidelines.

Fermentation, isolation, purification and biological activity of SJA-95, a heptaene polyene macrolide antibiotic produced by the Streptomyces sp. strain S24.

A new strain, Streptomyces sp. S24 was isolated from a soil sample collected from Japan. Preliminary morphological, cultural, physiological and biochemical studies on this strain were carried out. Under submerged culture conditions the strain produced heptaene polyene macrolide (SJA-95), which elicits promising antifungal activity in vitro against yeasts, filamentous fungi including clinical isolates and plant pathogens. Its antifungal activity is comparable to that of hamycin and amphotericin B. SJA-95 was found to be toxic when given by the parenteral route in mice and not absorbed by the oral route like other polyene heptaene macrolides. The physicochemical data, spectral studies and elemental analysis suggest that SJA-95 is a polyene macrolide antibiotic. However, the chemical structure needs to be elucidated by further spectroscopic studies viz. 13C NMR, FEB-MS, EL MS and other tests.