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BACKGROUND: Bauhinia variegata, a ayurvedic medicinal plant reported for its valuable effects in various diseases. It has shown significant effects in type 1 and type 2 diabetes. OBJECTIVE: The present work was designed to study effects of aqueous and alcoholic extract (AE and AlcE) of Bauhinia variegata Linn. leaves in diabetic neuropathy. METHODS: Male Sprague Dawley rats become diabetic using intraperitoneal injection of streptozotocin (STZ) at 55 mg/kg dose. After 6 weeks, animals were divided and were treated with AE and AlcE at a dose of 250, 500, and 1000 mg/kg (p. o.) for the next four weeks. Various parameters such as glucose, thermal hyperagesia, mechanical allodynia, MNCV and oxidative stess were assessed at the end of the study. RESULTS: Diabetic animals showed a significant reduction in response time in tail immersion and hot plate test as compared to animals in normal control group. AE and AlcE at 250, 500, and 1000 mg/kg dose significantly increased response time in the tail immersion test. Whereas, AE and AlcE at doses 500 and 1000 mg/kg showed significant improvement and in response time in the hot plate test. AlcE at 250, 500 and 1000 mg/kg dose increased the nociceptive threshold significantly. AE at doses 500 and 1000 mg/kg showed significant improvement in the nociceptive threshold. The decrease in motor nerve conduction velocity was observed in diabetic control animals, which was significantly improved after AlcE treatment as compared to AE treatment. Treatment with AE and AlcE decreased the lipid peroxidation and increased the antioxidant enzyme activity significantly in the sciatic nerve. CONCLUSION: The results showed that Bauhinia variegata extracts may be considered as a effective option for management of diabetic neuropathy.

Apocynin is a naturally occurring acetophenone, found in the roots of Apocynum cannabinum and Picrorhiza kurroa. Various chemical and pharmaceutical modifications have been carried out to enhance the absorption and duration of action of apocynin, like, formulation of chitosan-based apocynin-loaded solid lipid nanoparticles, chitosan-oligosaccharide based nanoparticles, and biodegradable polyanhydride nanoparticles. Apocynin has been subjected to a wide range of experimental screening and has proved to be useful for amelioration of a variety of disorders, like diabetic complications, neurodegeneration, cardiovascular disorders, lung cancer, hepatocellular cancer, pancreatic cancer, and pheochromocytoma. Apocynin has been primarily reported as an NADPH oxidase (NOX) inhibitor and prevents translocation of its p47phox subunit to the plasma membrane, observed in neurodegeneration and hypertension. However, recent studies highlight its off-target effects that it is able to function as a scavenger of non-radical oxidant species, which is relevant for its activity against NOX 4 mediated production of hydrogen peroxide. Additionally, apocynin has shown inhibition of eNOS-dependent superoxide production in diabetic cardiomyopathy, reduction of NLRP3 activation and TGFβ/Smad signaling in diabetic nephropathy, diminished VEGF expression and decreased retinal NF-κB activation in diabetic retinopathy, inhibition of P38/MAPK/Caspase3 pathway in pheochromocytoma, inhibition of AKT-GSK3β and ERK1/2 pathways in pancreatic cancer, and decreased FAK/PI3K/Akt signaling in hepatocellular cancer. This review aims to discuss the pharmacokinetics and mechanisms of the pharmacological actions of apocynin.

Objective: To prepare naringenin herbosome and evaluate its antidiabetic activity. Methods: Herbosomes were prepared by the solvent evaporation method. In vitro parameters like particle size, polydispersity index, zeta potential, and entrapment efficiency were estimated and in vitro diffusion study was performed. The in vivo studies were also performed in streptozotocin-induced diabetic male Sprague Dawley rats to evaluate blood glucose, total cholesterol, triglyceride, blood urea nitrogen, total protein, albumin level, aspartate aminotransferase, and alanine aminotransferase levels. Results: The optimized herbosome batch showed a particle size of 564.4 nm, a polydispersity index of 0.412, and zeta potential of -39.3 mV. The percentage entrapment of this formulation was 84.04%, with complete drug release within 8 h. Treatment of diabetic rats with naringenin herbosomes for 28 d significantly reduced the elevated level of plasma glucose as compared to plain naringenin. In biochemical parameters, the treatment showed a significant decrease in total cholesterol, triglyceride, and blood urea nitrogen; while elevated levels of aspartate aminotransferase and alanine aminotransferase were returned to normal. Pure naringenin and herbosome formulation at high dose increased the total protein whereas albumin level significantly increased in naringenin herbosomes at the highest dose but not in the pure naringenin treatment group. Conclusions: Naringenin herbosomes could improve the metabolic profile of diabetic rats, indicating enhanced antidiabetic activity of herbosome formulation.

Daidzein is a naturally occurring compound belonging to the class isoflavones and found in soya beans and other legumes. Acute oral toxicity was performed as per OECD guideline (TG 423) with slight...

An isocratic reverse phase HPLC method were described to determined chrysophanol contain in cassia tora meal powder obtained during the split manufacturing process of cassia tora seed husk and germs which are used as a valuable cattle feed and poultry feed as they are quite rich in protein. The method involves methanol: water (90:10) with 0.05% Ortho-Phosphoric acid as solvent system and chromatogram detection was done on 254 nm using photodiode array detector. Chrysophanol were extracted using methanol, 70% methanol, acid hydrolysis and Oxidative hydrolysis by different concentration of the Hydrochloric acid and ferric chloride respectively. An average chrysophanol content was observed in cassia tora meal powder was 0.066 percent. In an efforts to develop an improved method for the determination of content of chrysophanol which is important marker compound in cassia tora meal and also improve method of an extraction methods. The solvents for extraction of chrysophanol from cassia tora were examined in order to increase the chrysophanol contents in cassia tora meal powder. It was found that 70% methanol, 20% HCL (v/v) and 3% FeCl3 (v/v) was capable of increasing the chrysophanol contain up to 0.099 percent. Keywords: HPLC, Chrysophanol, Extraction, Cassia tora meal powder

Schiff's bases are condensation products of primary amines with carbonyl compounds. Schiff bases (imines) possess wide variety of biological activities that include antibacterial and antifungal activity. In present work, Schiff bases from 3,5- Dimethoxyphenol (aryloxy moiety) as starting material synthesized. Esterification of 3,5- Dimethoxyphenol led to formation of (3,5-Dimethoxy-phenoxy)-acetic acid ethyl ester (1). (3,5-Dimethoxy-phenoxy)-acetic acid hydrazide (2) is derived from Compound (1) by hydrazination. Compound (2) was reacted with different aromatic aldehydes to yield novel imines or Schiff bases (3A-I). The newly synthesized compounds were characterized on the basis of spectral studies and evaluated for antibacterial and antifungal activities. All the synthesized compounds had shown antibacterial and antifungal activity. Schiff bases 3C, 3D, 3E and 3I had shown good antimicrobial activity among all newly synthesized compounds. Keywords: Schiff base, aryloxy moiety, imines

The endothelial cells play a crucial role in the progression of angiogenesis, which causes cell re-modulation, proliferation, adhesion, migration, invasion and survival. Angiogenic factors like cytokines, cell adhesion molecules, growth factors, vasoactive peptides, proteolytic enzymes (metalloproteinases) and plasminogen activators bind to their receptors on endothelial cells and activate the signal transduction pathways like epidermal growth factor receptor (EGFR phosphatidylinositol 3-kinase and (PI3K)/AKT/mammalian target of rapamycin (mTOR) which initiate the process of angiogenesis. Cytokines that stimulate angiogenesis include direct and indirect proangiogenic markers. The direct proangiogenic group of markers consists of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and hepatocyte growth factor (HGF) whereas the indirect proangiogenic markers include transforming growth factor-beta (TGF-β), interleukin 6 (IL-6), interleukin 8 (IL-8) and platelet-derived growth factor (PDGF). VEGF and FGF-2 are the strongest activators of angiogenesis which stimulate migration and proliferation of endothelial cells in existing vessels to generate and stabilize new blood vessels. VEGF is released in hypoxic conditions as an effect of the hypoxia-inducible factor (HIF-1α) and causes re-modulation and inflammation of bronchi cell. Cell re-modulation and inflammation leads to the development of various lung disorders like pulmonary hypertension, chronic obstructive pulmonary disease, asthma, fibrosis and lung cancer. This indicates that there is a firm link between overexpression of VEGF and FGF-2 with lung disorders. Various natural and synthetic drugs are available for reducing the overexpression of VEGF and FGF-2 which can be helpful in treating lung disorders. Researchers are still searching for new angiogenic inhibitors which can be helpful in the treatment of lung disorders. The present review emphasizes on molecular mechanisms and new drug discovery focused on VEGF and FGF-2 inhibitors and their role as anti-angiogenetic agents in lung disorders.

Herein, we are reporting a facile route to synthesize magnetically separable copper loaded L-DOPA functionalized magnetite nanoparticles (Fe3O4-DOPA-CuNPs), which are well characterized by FT-IR, PXRD, SEM, EDAX, HRTEM, XPS, TGA and VSM techniques. This single catalyst exhibits excellent catalytic activity towards (i) synthesis of DHPMs via Biginelli reaction (ii) synthesis of imidazoles (iii) synthesis of 2-amino-4H-chromenes (iv) 1,2,3-triazole derivatives by ‘Click reaction’ under microwave irradiation (MWI). Interestingly it can be easily recovered and reused for subsequent cycles for above mentioned four important multicomponent reactions without any significant decrease in its catalytic activity.

The present work mainly deals with the study of blue colored dye, synthesized from an iridoid glycoside loganin from strychnos fruits (Strychnos nux-vomica). The efficacy of synthesized blue dye wa...

Diabetic retinopathy is one of the worst complications of diabetes and it is treated by invasive method. We prepared a surface modified poly (D, L-lactide-co-glycolide) i.e. PLGA nanoparticles for delivery of pioglitazone-a peroxisome proliferator-activated receptor-gamma agonist to posterior segment of the eye by topical administration. The present study investigated two grades of PLGA viz. 75:25 and 50:50. Surface modification was performed using polysorbate 80. Nanoparticles were prepared by single emulsion solvent evaporation method and optimized by using 3-factor 3-level Box-Behnken statistical design. Mean particle size, PDI and entrapment efficiency for optimized batch of PLGA 75:25 was found to be 163.23 nm, 0.286 and 91%, whereas; for PLGA 50:50 it was 171.7 nm, 0.280 and 93% respectively. DSC confirms the molecular dispersion of drug in polymer. In vitro release study showed biphasic drug release pattern with 58.48 ± 1.38% and 74.17 ± 1.38% cumulative drug release by PLGA 75:25 and 50:50 nanoparticles at the end of 10h. The release profile of pioglitazone from nanoparticles appeared to fit best with Higuchi model. In vivo study on rat showed dose dependent reduction in vascular endothelial growth factor concentration in vitreous fluid. The study reveals significance of peroxisome proliferator-activated receptor-gamma in management of diabetic retinopathy., Nanoparticle; PPAR-gamma; VEGF; diabetic retinopathy; Box-Behnken statistical design; PLGA; Nanomaterials; Pharmaceutical Science; Pharmacology; Ophthalmology; Alternative Medicine.

The present work envisages assessment of microwave assisted extraction (MAE) followed by comparison with that of conventional methods for effective extraction of colchicine from Gloriosa superba tu...

A simple, accurate, and precise bioanalytical method was developed and validated for the determination of pharmacokinetic parameters of sodium copper chlorophyllin, a USFDA approved food additive and colorant in rat plasma. The column used was Luna® C18 250×4.6 mm, 100 A, having particle size 4.5 μm, and the mobile phase used was methanol (MeOH), and 10 mM ammonium acetate buffer in the ratio of 90 : 10, the flow rate was 1 ml/min, and the injection volume of 20 μL. The retention time of sodium copper chlorophyllin was obtained at 9 min. The method was found to be linear at the range of 0.50-8.00 μg mL-1 .

Aim Present study focuses on the effect of daidzein in an experimental model of diabetic cardiomyopathy in rats. Materials and methods Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of STZ at dose 55 mg/kg. Daidzein treatment was started after six weeks of diabetes induction. Animals received daidzein at a dose of 25, 50, and 100 mg/kg orally for the next four weeks. Key findings Diabetic control animals showed significant prolongation in QT interval, PR interval, and R wave amplitude as compared to normal control animals. Treatment with daidzein at dose 100 mg/kg significantly normalized the QT interval, PR interval, and R wave amplitude. A significant reduction in QRS duration was observed in diabetic animals. Treatment with daidzein significantly improved the QRS duration after treatment. Hemodynamic parameters like systolic pressure (SBP), diastolic pressure (DBP) and mean atrial pressure (MAP) were found to be significantly decreased in diabetic animals. Treatment with daidzein at dose 100 mg/kg significantly improved the SBP, DBP, and MAP. Daidzein treatment prevented the loss of cardiac marker enzyme from heart tissue and also increased the level of AMPK and SIRT1 in plasma. Protein expression of NOX-4 and RAC-1 was also found to be reduced in cardiac tissue of daidzein treated animals. Daidzein treatment improved oxidative defense mechanism and reduced cardiac tissue necrosis and fibrosis. Significance From the results, it can be concluded that daidzein mitigates the progression of diabetic cardiomyopathy by inhibiting NOX-4 induced oxidative stress in cardiac tissue.

In this work, an optochromogenic receptor NC, (E)-2-(2-hydroxyethyl)-6-(2-(1-(6-nitro-2-oxo-2H-chromen-3-yl)ethylidene)hydrazinyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione has been designed and developed from 1,8-naphthalimide and 3-acetyl-6-nitro-2H-chromen-2-one moieties which provides multidimensional options for the rapid, selective, economical and reliable monitoring of fluoride in water (i.e. naked-eye, colorimetric, fluorometric, test strip, electrochemical and smartphone based response). Pick and choose assay process can be adopted depending upon the available instruments and skill of the analyzer impacting uniqueness to the developed receptor. Colorimetric detection of F− in water is possible, which can be monitored by UV-vis spectroscopy (detection limit as low as 8.468 × 10−7 M), test strips, and perceived by the naked eye. Excellent colorimetric response can be elucidated by augmented intramolecular charge transfer process within the molecule after anionic deprotonation interactions. The receptor exhibits a "turn-off" fluorescence response towards F− due to enhanced photoinduced charge transfer (PET) process with the detection limit up to 7.413 × 10−7 M. The binding interaction between receptor NC and F− is confirmed by DFT/TD-DFT calculations, 1H NMR and 19F NMR titration. The anodic and cathodic potential become flattened and shifted in NC + F− complex in the cyclic voltammetry study. Increased number of smartphone users and its user-friendly property initiated us to develop a simple and efficient protocol based on a digital image colorimetry using smartphones of different companies for the detection and quantification of fluoride ion. The lowest limit of detection from the smartphone protocol was found to be 3.368 × 10−6 M. A comparative study was carried out to check the versatility and accuracy of F− ion concentration determined through different microanalytical techniques. Fluoride ion concentration in real life samples like toothpaste, mouthwash, and groundwater collected from various regions were analyzed and found to be in agreement with standard Ion-selective electrode method. Thus, it holds promise for being developed as a futuristic tool for the real-time water quality monitoring.

Syngas to higher oxygenates conversion was carried out on a series of potassium-promoted cobalt-based catalysts. Catalysts with different potassium composition were prepared by metal organic framework-mediated synthesis, which is the calcination of the ZIF-67 metal organic framework (MOF). Cobalt skeleton structure that originated from the MOF is preserved after the calcination. The calcined catalysts consist of Co3O4 nanoparticles and surface carbon. The catalysts were reduced by H2/He prior to the reaction. CO hydrogenation was carried out at various temperatures (270 °C, 300 °C and 325 °C) and at 40 bar, with H2/CO = 1/1. The formation of methane and higher hydrocarbons is suppressed by potassium, and cobalt carbide is formed from metallic cobalt during the reaction. Thus, the K-promoted cobalt based catalyst synthesized by the MOF-mediated synthesis shows higher selectivity to ethanol, acetaldehyde and higher oxygenates, even at high temperatures.

SummaryBackground Oxidative stress is considered to be the initial event during the course of vitiligo. Catalase is mainly involved in the defense against oxidizing agents in the cell through detoxifying H2O2. Objectives Aims of the present study were 1) to assess the erythrocyte catalase activity and LPO levels, as well as CAT mRNA expression in skin and blood; 2) to investigate CAT promoter rs7943316, rs1001179; 5′-UTR rs1049982 and exon (rs17886350, rs11032709, rs17880442, rs35677492) polymorphisms and; 3) to perform genotype-phenotype/ haplotype correlation analyses, in vitiligo patients and controls from Gujarat. Methods Catalase activity and lipid peroxidation levels were measured spectrophotometrically. CAT mRNA levels were estimated using Real-time PCR by SYBR-Green method. SNP genotyping was performed using PCR-RFLP/ ARMS-PCR methods. Results Vitiligo patients showed significantly decreased CAT mRNA-expression in lesional, non-lesional skin and in blood with reduced catalase activity compared to that of controls. CAT -89A/T and -20T/C polymorphisms were significantly associated with patients, especially with active and generalized vitiligo whereas, no association was observed for -262G/A and exon polymorphisms. ‘A-262T-89C-20′ haplotype with variant alleles was found to be associated with 6.4-fold risk of vitiligo. Genotype/ haplotype-phenotype correlation analyses revealed that individuals with susceptible genotypes/ haplotype for CAT -89 A/T and -20 T/C polymorphisms showed significantly decreased catalase mRNA/activity, and only -89 A/T polymorphisms showed significantly increased lipid peroxidation levels, as compared to wild type genotypes/ haplotype. Conclusions In conclusion, the present study proposes the crucial role of catalase and its allelic variants in oxidative stress mediated pathogenesis of vitiligo. This article is protected by copyright. All rights reserved.

This study was undertaken to isolate and quantify aristolochic acid in Aristolochia indica stem and Apama siliquosa root. Aristolochic acid is an important biomarker component present in the Aristolochiaceae family. The isolation method involved simple solvent extraction, precipitation and further purification, using recrystallization. The structure of the compound was confirmed using infrared spectroscopy, mass spectrometry and nuclear magnetic resonance. A specific and rapid high-performance thin layer chromatography (HPTLC) method was developed for analysis of aristolochic acid. The method involved separation on the silica gel 60 F254 plates using the single solvent system of n-hexane: chloroform: methanol. The method showed good linear relationship in the range 0.4–2.0 μg/spot with r2 = 0.998. The limit of detection and limit of quantification were 62.841 ng/spot and 209.47 ng/spot, respectively. The proposed validated HPTLC method was found to be an easy to use, accurate and convenient method that could be successfully used for standardization and quality assessment of herbal material as well as formulations containing different species of the Aristolochiaceae family.

Thraustochytrids have predominantly been grown on hydrophilic substrates i.e. by “de novo” fermentation. The fatty acid composition of thraustochytrids oil in “de novo” mode is enriched in saturated palmitic acid and polyunsaturated docosahexaenoic acid. The “ex novo” fermentation of a novel Aurantiochytrium limacinum ICTSG-17 with waste acid oil altered the fatty acid composition of produced oil. This led to increased total unsaturated fatty acids (TUFA) and concomitant decrease in the total saturated fatty acids (TSFA) resulting in higher TUFA/TSFA ratio. However, cell growth and DHA content in “ex novo” were lower than that of “de novo” fermentation. Integration of “de novo” and “ex novo” fermentation modes were devised to attain high biomass and lipids enriched in DHA. Sequential “de novo”-“ex novo” fermentation resulted in ~20 g/L biomass and ~40% DHA content and higher TUFA/TSFA ratio as compared to that of “de novo” mode.

The superalloys are the better candidate materials for the high temperature application due to their superior mechanical strength and higher corrosion resistance at service temperature. Nickel-based superalloys are used as components of gas turbines of jet engines. Since these components are subjected to high temperature, their performance is drastically affected by environmental conditions. The studies were performed on bare Substrate as well as on coated samples in the super heater zone of a coal fired boiler where the temperature was around 700±10°C for 500 hours. The morphologies of the scale and compositional analysis were characterized by using Atomic Force Microscopy, XRD and field emission scanning electron microscopy / energy dispersive analysis. The coated specimen showed good adherence to the substrate with negligible microspalling of the scales. The nanostructured coating imparted better hot corrosion resistance than the bare substrate in the given environment.

Digital data has changed the use and access of information. Everyday lot of data is produced and this requires highdensity storage devices which can retain values for a long time[1]. Deoxyribonucleic acid (DNA) can be potentially used for these purposes as it is not much different from the conventional method used in a computer. DNA can be used as a robust and high-density storage device even under unfavourable conditions[2]. Theoretically, one can encode 2 bits per nucleotide in DNA which can store 455 exabytes per gram maximum data in single-stranded DNA (ssDNA)[3]. In this paper, the method described can be used to store text data in DNA by compressing, storing multiple copies along with providing security to data. General Terms Storage method and compression.

Rheum emodi —a culinary plant used across the world, is known to contain bioactive anthraquinoids which find extensive use in the chemical, pharmaceutical and cosmetic industry and exhibit diverse pharmacological actions. The current work envisages development of a microwave assisted extraction (MAE) for extraction of total anthraquinones (AQs) and five 1,8-dihydroxyanthraquinones (DHAQs) from Rheum emodi. In the initial part of the work, a rapid and facile method was developed for determining total AQs using UV spectroscopy. Preliminary screening experiments were performed to select choice of solvent, extraction time, microwave power and solvent: sample ratio. Subsequently, optimum conditions for MAE were determined using RSM by employing a Box-Behnken design. Extraction rate of total AQs and five DHAQs reached maximum at time 7.5 min, microwave power 490 W, solvent: sample ratio 15: 0.1 ml/g and concentration of aqueous NaOH solution 0.255 M. Furthermore, MAE offered significantly higher yields for total AQs and five DHAQs and also a high DPPH-scavenging and hydrogen peroxide scavenging potential than the extracts obtained by conventional extraction methods. The proposed method was fast, energy-saving, environment-friendly and can find a potential industrial use in the extraction of the bioactive DHAQs.

The present study investigates the cardioprotective activity of the Macrotyloma uniflorum seed extract (MUSE) and its phenolic acids (p-coumaric acid and ferulic acid) in isoproterenol (ISO)-induced myocardial infarction in rats. The previously mentioned phenolic acids were isolated and quantified from MUSE by HPLC. Pretreatment of gemfibrozil (reference standard), MUSE (250 and 500 mg/kg) and the phenolic acids for 30 days to rats treated with ISO (85 mg/kg) on the last 2 days resulted in a significant attenuation of the ISO-elevated levels of serum marker enzymes (aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase MB), total cholesterol, triglycerides, uric acid, C-reactive protein and malondialdehyde and a restoration of the levels of the ISO-depleted marker enzymes, reduced glutathione and the antioxidant enzymes-superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in heart. Restoration of the ISO-altered electrocardiogram pattern and haemodynamic parameters (left ventricular end diastolic pressure, heart rate, systolic, diastolic and mean arterial pressure) was also brought about by treatment with MUSE and the phenolic acids. It may be concluded that MUSE treatment to ISO-challenged rats exhibits a significant cardioprotective effect probably because of the potent antioxidant activity of its phenolic acids that salvage the myocardium from the deleterious effects of ISO. Copyright © 2016 John Wiley & Sons, Ltd.

A novel hydrazone Schiff's base, (E)-6-(2-(2,4-dihydroxybenzylidene)hydrazinyl)-2-(2-hydroxyethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione, DHB based on 1,8-naphthalimide has been designed and synthesized that acts as a dual mode chromofluorogenic sensor with a noticeable color change from orange to blue and fluorometric “turn-off” response towards F− with high sensitivity and selectivity. A detailed study to establish the binding mechanism of the receptor DHB with F− ion has been carried out by visual colorimetric (naked eye), UV–visible and fluorescence spectroscopy which was then further validated by 1H NMR titration studies and theoretical calculations. Interestingly, color response towards chromogenic model formed between receptor DHB and F− ion were explored by reading RGB values of digital image using smartphone. Smartphones based quantification of F− minimizes expensive, sophisticated instruments handled by trainers and provide the simple, cheap, rapid, handy, and easy available analytical tool that any person can easily use in remote areas. Test strips validate that DHB acts as a cheaper and proficient solid-state probe for the quantification of F− ion. The association constant and limit of detection for F− were determined as 0.817 × 1013 M−3 and 1.34 nM respectively. Further, the proposed smartphone-based method quantified fluoride in real water samples and obtained promising results that make it a more futuristic, hassle free and straightforward approach to the common man without requiring a skilled person to monitor F− in environmental water samples.

Dry eye disorder is the most common ophthalmic complication which has already affected millions of people worldwide. Due to protective response of eye, conventional drops get rapidly eliminated from eye site. Moreover; current treatment of dry eye syndrome demands frequent administration of formulation. Henceforth; there is need to develop novel ocular drug delivery system to meet the need. By considering the involvement of Peroxisome proliferator-activated receptor-γ in dry eye, we prepared Pioglitazone loaded Poly (D, L-lactide-co-glycolide) nanoparticles which were then suspended in temperature sensitive in situ gel prepared by combination of Poloxamer 407 and HPMC K4M those also contribute in treatment as lubricant. Nanoparticle system and in situ formulation was optimised by 32 factorial design. Optimized nanoparticle system was evaluated for particle size, PDI, % entrapment efficiency, XRD, DSC and then suspended in polymeric in situ gel. In situ gel was characterized by viscosity, %drug release, gelation temperature, gelling strength, sterility test, preservative efficacy test. Ocular irritation potential was confirmed by histology study on goat eye cornea. Formulation retained the normal structure of cornea and found non-irritant. Effectiveness of optimised formulation in comparison to existing marketed formulation was estimated by Schirmer’s test on mice. Prepared formulation showed induced tear production and further stabilised tear film for long period in comparison to marketed formulation. It can be concluded that prepared formulation can be consider as alternative for existing treatment.

The present study was designed to check the effect of daidzein in the management of diabetic retinopathy.Streptozotocin at dose 55 mg/kg was used for inducing diabetes in rats. After 28 days of diabetic induction, animals were treated with daidzein at dose 25, 50, and 100 mg/kg for the next 28 days. Electroretinography, estimation of plasma glucose, lactate dehydrogenase, aldose reductase, sorbitol dehydrogenase and oxidative stress parameters were performed at the end of the study. Histopathology of retina was carried out at the end of the study.Diabetic control animals showed a significant increase in levels of plasma glucose and plasma lactate dehydrogenase (p 0.001). Treatment with daidzein at a dose of 50 and 100 mg/kg significantly reduced the elevated level of blood glucose (p 0.01 and p 0.01). Whereas, treatment with daidzein at a dose 100 mg/kg significantly reduced the elevated level of lactate dehydrogenase in plasma after 28 days of treatment (p 0.01). Treatment with daidzein at a dose of 100 mg/kg significantly reduced the level of aldose reductase and sorbitol dehydrogenase (p 0.01 and p 0.001 respectively). Electroretinography revealed that daidzein treatment at a dose of 100 mg/kg significantly prevented the change in 'a' and 'b' wave amplitude and latency. Oxidative stress was also found to be significantly reduced after 28 days of daidzein treatment. Histopathological findings showed a reduction in retinal thickness after daidzein treatment.Daidzein treatment protected retina from damage in hyperglycaemic conditions. Thus, Daidzein can be considered as an effective treatment option for diabetic retinopathy.

The human body has a mechanism for balancing the generation and neutralization of reactive oxygen species. The body is exposed to many agents that are responsible for the generation of reactive oxygen/nitrogen species, which leads to disruption of the balance between generation of these species and oxidative stress defence mechanisms. Diabetes is a chronic pathological condition associated with prolonged hyperglycaemia. Prolonged elevation of level of glucose in the blood leads to the generation of reactive oxygen species. This generation of reactive oxygen species is responsible for the development of diabetic vasculopathy, which includes micro- and macrovascular diabetic complications. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a membrane-bound enzyme responsible for the development of reactive oxygen species in hyperglycaemia. Phosphorylation of the cytosolic components of NOX, such as p47phox, p67phox, and RAC-1, in hyperglycaemia is one of the important causes of conversion of oxygen to reactive oxygen. Overexpression of NOX in pathological conditions is associated with activation of aldose reductase, advanced glycation end products, protein kinase C and the hexosamine pathway. In addition, NOX also promotes the activation of inflammatory cytokines, such as TGF-β, TNF-α, NF-kβ, IL-6, and IL-18, the activation of endothelial growth factors, such as VEGF and FGF, hyperlipidaemia, and the deposition of collagen. Thus, overexpression of NOX is linked to the development of diabetic complications. The present review focuses on the role of NOX, its associated pathways, and various NOX inhibitors in the management and treatment of diabetic complications, such as diabetic nephropathy, retinopathy, neuropathy and cardiomyopathy.

Plumbagin, a naturally occurring naphthoquinone derivative, is known to possess various pharmacological activities. A rapid, sensitive, and specific high-performance liquid chromatographic method using fluorescence detection is reported for the determination of plumbagin in two Plumbago species and five polyherbal formulations. The method employed a reverse phase C18 column with isocratic elution using 65:35 pH 3.2 methanol and 0.1% aqueous o-phosphoric acid at a flow rate of 1.0 mL/min. Plumbagin displayed maximal fluorescence with excitation at 264 nm and emission at 605 nm. A linear calibration relationship was obtained for 1 to 10 µg/mL plumbagin with limits of detection and quantitation of 8 ng/mL and 30 ng/mL, respectively. The relative standard deviation values for intraday and interday precision were less than 2%. The recoveries were greater than 97% with relative standard deviations less than 3%. This is the first study to employ high-performance liquid chromatography with fluorescence detection ...

Rheum emodi is principally known to consist 1,8-dihydroxyanthraquinones (DHAQs) that find immense use in the chemical, pharmaceutical, cosmetic industries and in herbal medication and food sector. The aim of this study was to compare non-conventional and classical methods for extraction of anthraquinones from R. emodi. Optimisation of the extraction parameters for various methods was done and their extraction efficiency was evaluated. In preliminary screening experiments, choice of solvent and solid : solvent ratio was optimised. Comparison of extraction efficiency for classical methods like maceration, heat-reflux, soxhletion and non-conventional methods like ultra-sonication and sublimation was done for five DHAQs - aloe emodin, rhein, emodin, chrysophanol and physcion using HPLC-UV and fluorescence detection in native and acid hydrolysed samples. It was observed that ethanol was the best solvent for extraction of anthraquinones with a solid : solvent ratio of 1:20. A prior acid hydrolysis led to significant increase in anthraquinone extraction. Among the extraction methods heat reflux for 45 min was the most prominent extraction method with highest recovery of the DHAQs. In ultrasonic assisted extraction, an increase in the anthraquinone extraction was seen till 45 min after which the concentration declined. A novel, solvent-free, green and selective method of extraction by sublimation was found to be effective for extraction of anthraquinones.

Rheum emodi is used as a culinary plant across the world and finds an eminent role in the Ayurvedic and traditional Chinese systems of medicine. The plant is known to principally contain 1,8-dihydroxyanthraquinones (DHAQs) like rhein, aloe emodin, emodin, chrysophanol and physcion that possess diverse pharmacological and therapeutic actions. The present work deals with developing a platform technology for isolation of these DHAQs and evaluating their anti-diabetic potential. Herein, we report the anti-hyperglycemic activity and alpha glucosidase (AG) inhibitory actions of five isolated DHAQs from R. emodi. All the five isolated DHAQs showed good anti-hyperglycemic activity with aloe emodin exhibiting maximum lowering of blood glucose in an oral glucose tolerance test. However, on evaluation of the AG inhibitory potential of the DHAQs only emodin exhibited potent intestinal AG inhibition (93 ± 2.16%) with an IC50 notably lower than acarbose. Subsequent kinetic studies indicated a mixed type of inhibition for emodin. In vivo studies using oral maltose load showed almost total inhibition for emodin when compared to acarbose. Molecular docking studies revealed the presence of an allosteric topographically distinct 'quinone binding site' and showed that interaction with Ser 74 occurs exclusively with emodin, which is vital for AG inhibition. The net benefit from the glucose lowering effect and mixed type inhibition by emodin would enable the administration of a small dosage that is safe and non-toxic in the case of prolonged use in treating diabetes.

Introduction: Alzheimer′s disease (AD) has increased at an alarming rate and is now a worldwide health problem. Inhibitors of acetylcholinesterase (AChE) leading to inhibition of acetylcholine breakdown constitute the main therapeutic strategy for AD. Psoralen was investigated as inhibitor of AChE enzyme in an attempt to explore its potential for the management of AD. Materials and Methods: Psoralen was isolated from powdered Psoralea corylifolia fruits. AChE enzyme inhibitory activity of different concentrations of psoralen was investigated by use of in vitro enzymatic and molecular docking studies. Further, the enzyme kinetics were studied using Lineweaver-Burk plot. Results: Psoralen was found to inhibit AChE enzyme activity in a concentration-dependent manner. Kinetic studies showed psoralen inhibits AChE in a competitive manner. Molecular docking study revealed that psoralen binds well within the binding site of the enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein. Conclusion: The result of AChE enzyme inhibitory activity of the psoralen in this study is promising. It could be further explored as a potential candidate for further development of new drugs against AD.

Editing in microRNAs, particularly in seed can significantly alter the choice of their target genes. We show that out of 13 different human tissues, different regions of brain showed higher adenosine to inosine (A-to-I) editing in mature miRNAs. These events were enriched in seed sequence (73.33%), which was not observed for cytosine to uracil (17.86%) editing. More than half of the edited miRNAs showed increased stability, 72.7% of which had ΔΔG values less than −6.0 Kcal/mole and for all of them the edited adenosines mis-paired with cytosines on the pre-miRNA structure. A seed-editing event in hsa-miR-411 (with A – C mismatch) lead to increased expression of the mature form compared to the unedited version in cell culture experiments. Further, small RNA sequencing of GBM patients identified significant miRNA hypoediting which correlated with downregulation of ADAR2 both in metadata and qRT-PCR based validation. Twenty-two significant (11 novel) A-to-I hypoediting events were identified in GBM samples. This study highlights the importance of specific sequence and structural requirements of pre-miRNA for editing along with a suggestive crucial role for ADAR2. Enrichment of A-to-I editing in seed sequence highlights this as an important layer for genomic regulation in health and disease, especially in human brain.

The creation of single, negatively charged silicon vacancy ( SiV −) centers in well-defined diamond layers close to the host surface is a crucial step for the development of diamond-based quantum optic devices with many applications in nanophotonics, quantum sensing, or quantum information science. Here, we report on the creation of shallow (10 nm below the surface), single SiV − centers in diamond using low energy Si + ion implantation with subsequent high temperature annealing at 1500 °C. We show transition linewidths down to 99 MHz and narrow inhomogeneous distributions. Furthermore, we achieved a reduction of homogeneous linewidths by a factor of 2 after removing subsurface damage using oxygen plasma processing. These results not only give insights into the formation process of SiV − centers but also indicate a favorable processing method to fabricate shallow single quantum emitters in diamond perfectly suited for coupling to nanostructures on the diamond surface.

The aim of the study was to isolate important bioactive phenethylisoquinoline alkaloid, colchicine, from Gloriosa superba (Liliaceae) tubers. A facile and efficient method for isolation of proto alkaloid, colchicine, involves defatting, solvent extraction of the dried tuber powder and further purification by recrystallization. The compound was characterized and confirmed by Thin Layer Chromatography, ultraviolet spectroscopy, infrared spectroscopy, mass spectroscopy and Nuclear Magnetic Resonance (NMR) analysis. The proposed method can be used for isolation of colchicine on a commercial scale from G. superba tubers.

The surge of interest in naturally occurring phytochemicals with high therapeutic potential has led to the discovery of many molecules, out of which naturally occuring coumarins such as marmelosin, umbelliferone and scopoletin present in Aegle marmelos (Bael) fruit shows good therapeutic potential. The aim of the present work is to develop and validate Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) method for simultaneous determination of marmelosin, umbelliferone and scopoletin in A. marmelos fruit extracts. The chromatographic separation was performed with isocratic elution of 55:45 (%, v/v) methanol-water containing 0.1 % acetic acid as mobile phase. The method used to analyse the extract of A. marmelos showed good resolution with retention time within 12 min. The relative concentrations of above phytoconstituent were determined in A. marmelos fruits. The method was found to give compact peaks for scopoletin, umbelliferone and marmelosin (Rt of 4.6, 6.5 and 11.3 min respectively) and were linear over the range 5-30 μg ml(-1) (R(2) = 0.9655), 2-10 μg ml(-1) (R(2) = 0.9964) and 2-10 μg ml(-1) (R(2) = 0.9862) respectively. The mean recoveries for marmelosin, umbelliferone and scopoletin at three concentrations were in the range of 98.8-102.9, 98.8-101.1 and 94.2-98.3 % respectively. The relative standard deviation of accuracy, precision and repeatability were within 2 %, indicating the method produced highly reproducible results. Therefore this simple, precise and accurate method enables simultaneous separation of this phytoconstituent and hence can be successfully applied in analysis and routine quality control of herbal material and formulation containing A. marmelos.

A series of alkyl derivatives of plumbagin (2-methyl-5-hydroxy-1,4-naphthoquinone), analogous to Vitamin K, have been synthesized. Plumbagin reacts with carboxylic acid in presence of silver nitrate and ammonium peroxydisulphate to form its alkyl derivatives. The compounds synthesized were characterized by MS, IR, 1 H and 13C-NMR Spectroscopy. The derivatives prepared may find application as antithrombotic agents and may facilitate designing of similar newer analogues.

Droserone (2,5-dihyrdoxy-3-methyl-1,4- naphthoquinone) was prepared from naturally occurring naphthoquinone plumbagin. Plumbagin was isolated from roots of Plumbago zeylanica. Plumbagin was first brominated at C-3 which was subsequently substituted with hydroxy group by a nucleophilic substitution to obtain Droserone. The synthesized compounds were characterized by IR, MS, 1H and 13C NMR spectral data. RP-HPLC was used to ascertain the purity of the obtained compound.

Because of the avoidance of first pass metabolic effects due to direct and rapid absorption with improved permeability, intranasal route represents a good alternative for extravascular drug administration. The aim of the study was to investigate the intranasal pharmacokinetics of two anti-migraine drugs (zolmitriptan and eletriptan), using retro-orbital sinus and jugular vein sites sampling. In a parallel study design, healthy male Sprague-Dawley (SD) rats aged between 8 and 12weeks were divided into groups (n=4 or 5/group). The animals of individual groups were dosed intranasal (~1.0mg/kg) and oral doses of 2.1mg/kg of either zolmitriptan or eletriptan. Serial blood sampling was performed from jugular vein or retro-orbital site and plasma samples were analyzed for drug concentrations using LC-MS/MS assay. Standard pharmacokinetics parameters such as Tmax, Cmax, AUClast, AUC0-inf and T1/2 were calculated and statistics of derived parameters was performed using unpaired t-test. After intranasal dosing, the mean pharmacokinetic parameters Cmax and AUCinf of zolmitriptan/eletriptan showed about 17-fold and 3-5-fold higher values for retro-orbital sampling as compared to the jugular vein sampling site. Whereas after oral administration such parameters derived for both drugs were largely comparable between the two sampling sites and statistically non-significant. In conclusion, the assessment of plasma levels after intranasal administration with retro-orbital sampling would result in spurious and misleading pharmacokinetics.

Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis, linked with both genetic and non-genetic factors. The precise modus operandi for vitiligo pathogenesis has remained elusive. Theories regarding loss of melanocytes are based on autoimmune, cytotoxic, oxidant-antioxidant and neural mechanisms. Reactive oxygen species (ROS) in excess have been documented in active vitiligo skin. Numerous proteins in addition to tyrosinase are affected. It is possible that oxidative stress is one among the main principal causes of vitiligo. However, there also exists ample evidence for altered immunological processes in vitiligo, particularly in chronic and progressive conditions. Both innate and adaptive arms of the immune system appear to be involved as a primary event or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The article focuses on the scientific evidences linking oxidative stress and immune system to vitiligo pathogenesis giving credence to a convergent terminal pathway of oxidative stress-autoimmunity-mediated melanocyte loss.

The aim of the present work was to develop and validate a reversed-phase high-performance liquid chromatography method for the simultaneous estimation of picroside I, plumbagin, and Z-guggulsterone in a polyherbal formulation containing Picrorhiza kurroa, Plumbago zeylanica, and Commiphora wightii extracts. The analysis was performed on a C18 column using the mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% orthophosphoric acid in water) with the following gradient: 0-12 min, 25% A; 12-17 min, 25-80% A; 17-32 min, 80% A; and 32-37 min, 80-25% A at a flow rate of 1 ml/min. Ultraviolet detection was at 255 nm. The method was validated for accuracy, precision, linearity, specificity, and sensitivity as per the norms of the International Conference on Harmonization. From the validation study, it was found that the method is specific, accurate, precise, reliable, and reproducible. Good linear correlation coefficients (r 2 >0.900) were obtained for calibration plots in the ranges tested. Limits of detection were 2.700, 0.090 and 0.099 μg/ml and limits of quantification were 9.003, 0.310, and 0.330 μg/ml for picroside I, plumbagin, and Z-guggulsterone, respectively. Intra and interday relative standard deviation (RSD) of retention times and peak areas was less than 3.0%. Recovery was found to be 100.21% for picroside I, 102.5% for plumbagin, and 103.84% for Z-guggulsterone. The established method was appropriate and the three markers were well resolved, enabling efficient quantitative analysis of picroside I, plumbagin and Z-guggulsterone. The method is a rapid and cost-effective quality control tool for routine quantitative analysis of picroside I, plumbagin, and Z-guggulsterone in tablet dosage form.

Autophagy degrades and is thought to recycle proteins, other macromolecules, and organelles. In genetically engineered mouse models (GEMMs) for Kras-driven lung cancer, autophagy prevents the accumulation of defective mitochondria and promotes malignancy. Autophagy-deficient tumor-derived cell lines are respiration-impaired and starvation-sensitive. However, to what extent their sensitivity to starvation arises from defective mitochondria or an impaired supply of metabolic substrates remains unclear. Here, we sequenced the mitochondrial genomes of wild-type or autophagy-deficient (Atg7−/−) Kras-driven lung tumors. Although Atg7 deletion resulted in increased mitochondrial mutations, there were too few nonsynonymous mutations to cause generalized mitochondrial dysfunction. In contrast, pulse-chase studies with isotope-labeled nutrients revealed impaired mitochondrial substrate supply during starvation of the autophagy-deficient cells. This was associated with increased reactive oxygen species (ROS), lower energy charge, and a dramatic drop in total nucleotide pools. While starvation survival of the autophagy-deficient cells was not rescued by the general antioxidant N-acetyl-cysteine, it was fully rescued by glutamine or glutamate (both amino acids that feed the TCA cycle and nucleotide synthesis) or nucleosides. Thus, maintenance of nucleotide pools is a critical challenge for starving Kras-driven tumor cells. By providing bioenergetic and biosynthetic substrates, autophagy supports nucleotide pools and thereby starvation survival.

Study was undertaken with an objective to develop a simple method for isolation of ursolic acid from Nerium indicum Mill leaves and to prepare synthetic derivatives of ursolic acid. The leaves were defatted with petroleum ether and then extracted with methanol. Methanol extract was basified and subsequently acidified, followed by charcoal treatment to isolate ursolic acid. Synthetic derivatives were prepared from isolated ursolic acid by substitution at C-3 position. The structure of ursolic acid and its derivatives were confirmed by IR, MS, 1H NMR, 13C NMR studies.