Nickel toxicity pretreatment attenuates salt stress by activating antioxidative system and ion homeostasis in tomato (Solanum lycopersicon L.): an interplay from mild to severe stress.

Plants antioxidative system is the first line of defense against oxidative stress caused secondarily by toxic ions under salinity. Plants with pre-activated antioxidative system can better adapt to salinity and can result in higher growth and yield. The current experiment was conducted to assess the adaptation of two tomato genotypes (Riogrande and Green Gold) with pre-activated antioxidative enzymes against salt stress. Tomato seedlings were exposed to mild stress (Ni: 0, 15 and 30 mg L-1) for three weeks to activate the antioxidative enzymes. The seedlings with pre-activated antioxidative enzymes were then grown under severe stress in hydroponics (0, 75 and 150 mM NaCl) and soil (control, 7.5 and 15 dS m-1) to check the adaptation, growth and yield. The results showed that Ni toxicity significantly enhanced activities of antioxidant enzymes (SOD, CAT, APX and POX) in both the genotypes and reduced growth with higher values in genotype Riogrande than Green Gold. The seedlings with pre-activated antioxidant enzymes showed better growth, low Na+ and high K+ uptake and maintained higher antioxidative enzymes activity than non-treated seedlings after four weeks of salt stress treatment in hydroponics. Similarly, the results in soil salinity treatment of the Ni pretreated seedlings showed higher yield characteristics (fruit yield per plant, average fruit weight and fruit diameter) than non-treated seedlings. However, Ni pretreatment had nonsignificant effect on tomato fruit quality characteristics like fruit dry matter percentage, total soluble solids, fruit juice pH and titratable acidity. The genotype Riogrande showed better growth, yield and fruit quality than Green Gold due to higher activity of antioxidant enzymes and better ion homeostasis as a result of Ni pretreatment. The results suggest that pre-activation antioxidant enzymes by Ni treatment proved to be an effective strategy to attenuate salt stress for better growth and yield of tomato plants.

In Vitro and In Vivo Anti-Arthritic Potential of Caralluma tuberculata N. E. Brown. and Its Chemical Characterization.

Present research was planned to assess the in vitro and in vivo anti-arthritic potential of Caralluma tuberculata N. E. Brown. methanolic (CTME) and aqueous (CTAQ) extracts. Chemical characterization was done by high-performance liquid chromatography and gas chromatography−mass spectrometry analysis. The Complete Freund's Adjuvant (CFA) was injected in left hind paw of rat at day 1 and dosing at 150, 300 and 600 mg/kg was started on the 8th day via oral gavage in all groups except normal and disease control rats (which were given distilled water), whereas methotrexate (intraperitoneal; 1 mg/kg/mL) was administered to standard control. The CTME and CTAQ exerted significant (p < 0.01−0.0001) in vitro anti-arthritic action. Both extracts notably reduced paw edema, and restored weight loss, immune organs weight, arthritic score, RBCs, ESR, platelet count, rheumatoid factor (RF), C-reactive protein, and WBCs in treated rats. The plant extracts showed significant (p < 0.05−0.0001) downregulation of tumor necrosis factor-α, Interleukin-6, -1ß, NF-κB, and cyclooxygenase-2, while notably upregulated IL-4, IL-10, I-κBα in contrast to disease control rats. The plant extracts noticeably (p < 0.001−0.0001) restored the superoxide dismutase and catalase activities and MDA levels in treated rats. Both extracts exhibited significant anti-arthritic potential. The promising potential was exhibited by both extracts probably due to phenolic, and flavonoids compounds.

Silicon-nanoparticles doped biochar is more effective than biochar for mitigation of arsenic and salinity stress in Quinoa: Insight to human health risk assessment.

The increasing contamination of soil with arsenic (As), and salinity has become a menace to food security and human health. The current study investigates the comparative efficacy of plain biochar (BC), and silicon-nanoparticles doped biochar (SBC) for ameliorating the As and salinity-induced phytotoxicity in quinoa (Chenopodium quinoa Willd.) and associated human health risks. Quinoa was grown on normal and saline soils (ECe 12.4 dS m-1) contaminated with As (0, 20 mg kg-1) and supplemented with 1% of BC or SBC. The results demonstrated that plant growth, grain yield, chlorophyll contents, and stomatal conductance of quinoa were decreased by 62, 44, 48, and 66%, respectively under the blended stress of As and salinity as compared to control. Contrary to this, the addition of BC to As-contaminated saline soil caused a 31 and 25% increase in plant biomass and grain yield. However, these attributes were increased by 45 and 38% with the addition of SBC. The H2O2 and TBARS contents were enhanced by 5 and 10-fold, respectively under the combined stress of As and salinity. The SBC proved to be more efficient than BC in decreasing oxidative stress through overexpressing of antioxidant enzymes. The activities of superoxide dismutase, peroxidase, and catalase were enhanced by 5.4, 4.6, and 11-fold with the addition of SBC in As-contaminated saline soil. Contamination of grains by As revealed both the non-carcinogenic and carcinogenic risks to human health, however, these effects were minimized with the addition of SBC. As accumulation in grains was decreased by 65-fold and 25-fold, respectively for BC and SBC in addition to As-contaminated saline soil. The addition of SBC to saline soils contaminated with As for quinoa cultivation is an effective approach for decreasing the food chain contamination and improving food security. However, more research is warranted for the field evaluation of the effectiveness of SBC in abating As uptake in other food crops cultivated on As polluted normal and salt-affected soils.

Pterostilbene improves CFA-induced arthritis and peripheral neuropathy through modulation of oxidative stress, inflammatory cytokines and neurotransmitters in Wistar rats.

Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.

Novel and Alternative Therapeutic Strategies for Controlling Avian Viral Infectious Diseases: Focus on Infectious Bronchitis and Avian Influenza.

The growth of poultry farming has enabled higher spread of infectious diseases and their pathogens among different kinds of birds, such as avian infectious bronchitis virus (IBV) and avian influenza virus (AIV). IBV and AIV are a potential source of poultry mortality and economic losses. Furthermore, some pathogens have the ability to cause zoonotic diseases and impart human health problems. Antiviral treatments that are used often lead to virus resistance along with the problems of side effects, recurrence, and latency of viruses. Though target hosts are being vaccinated, the constant emergence and re-emergence of strains of these viruses cause disease outbreaks. The pharmaceutical industry is gradually focusing on plant extracts to develop novel herbal drugs to have proper antiviral capabilities. Natural therapeutic agents developed from herbs, essential oils (EO), and distillation processes deliver a rich source of amalgams to discover and produce new antiviral drugs. The mechanisms involved have elaborated how these natural therapeutics agents play a major role during virus entry and replication in the host and cause inhibition of viral pathogenesis. Nanotechnology is one of the advanced techniques that can be very useful in diagnosing and controlling infectious diseases in poultry. In general, this review covers the issue of the poultry industry situation, current infectious diseases, mainly IB and AI control measures and, in addition, the setup of novel therapeutics using plant extracts and the use of nanotechnology information that may help to control these diseases.

Senna makki and other active phytochemicals: Myths and realities behind covid19 therapeutic interventions.

This study aims to investigate the binding potential of chemical compounds of Senna in comparison with the experimentally tested active phytochemicals against SARS-CoV-2 protein targets to assist in prevention of infection by exploring multiple treatment options. The entire set of phytochemicals from both the groups were subjected to advanced computational analysis that explored functional molecular descriptors from a set of known medicinal-based active therapeutics followed by MD simulations on multiple SARS-CoV-2 target proteins. Our findings manifest the importance of hydrophobic substituents in chemical structures of potential inhibitors through cross-validation with the FDA-approved anti-3CLpro drugs. Noteworthy improvement in end-point binding free energies and pharmacokinetic profiles of the proposed compounds was perceived in comparison to the control drug, vizimpro. Moreover, the identification of common drug targets namely; AKT1, PTGS1, TNF, and DPP4 between proposed active phytochemicals and Covid19 using network pharmacological analysis further substantiate the importance of medicinal scaffolds. The structural dynamics and binding affinities of phytochemical compounds xanthoangelol_E, hesperetin, and beta-sitosterol reported as highly potential against 3CLpro in cell-based and cell-free assays are consistent with the computational analysis. Whereas, the secondary metabolites such as sennosides A, B, C, D present in higher amount in Senna exhibited weak binding affinity and instability against the spike protein, helicase nsp13, RdRp nsp12, and 3CLpro. In conclusion, the results contravene fallacious efficacy claims of Senna tea interventions circulating on electronic/social media as Covid19 cure; thus emphasizing the importance of well-examined standardized data of the natural products in hand; thereby preventing unnecessary deaths under pandemic hit situations worldwide.

Potassium and Silicon Synergistically Increase Cadmium and Lead Tolerance and Phytostabilization by Quinoa through Modulation of Physiological and Biochemical Attributes.

Cadmium (Cd) and lead (Pb) contaminated soils have increased recently, resulting in limited crop productivity. The ameliorative role of potassium (K) and silicon (Si) is well established in plants under heavy metals stress; however, their combined role under the co-contamination of Cd and Pb is not well understood. We hypothesized that the synergistic application of K and Si would be more effective than their sole treatment for increasing the Pb and Cd tolerance and phytostabilization potential of quinoa (Chenopodium quinoa Willd.). In the current study, quinoa genotype 'Puno' was exposed to different concentrations of Cd (0, 200 µM), Pb (0, 500 µM) and their combination with or without 10 mM K and 1.0 mM Si supplementation. The results revealed that the combined stress of Cd and Pb was more detrimental than their separate application to plant biomass (66% less than the control), chlorophyll content and stomatal conductance. Higher accumulation of Pb and Cd led to a limited uptake of K and Si in quinoa plants. The supplementation of metal-stressed plants with 10 mM K and 1.0 mM Si, particularly in combination, caused a significant increase in the growth, stomatal conductance and pigment content of plants. The combined stress of Cd and Pb resulted in an overproduction of H2O2 (11-fold) and TBARS (13-fold) and a decrease in membrane stability (59%). Oxidative stress induced by metals was lessened by 8-fold, 9-fold, 7-fold and 11-fold increases in SOD, CAT, APX and POD activities, respectively, under the combined application of K and Si. It is concluded that the exogenous supply of K and Si in combination is very promising for increasing Cd and Pb tolerance and the phytostabilization potential of quinoa.

Formulation and Evaluation of a Clove Oil-Encapsulated Nanofiber Formulation for Effective Wound-Healing.

Wound-healing is complicated process that is affected by many factors, especially bacterial infiltration at the site and not only the need for the regeneration of damaged tissues but also the requirement for antibacterial, anti-inflammatory, and analgesic activity at the injured site. The objective of the present study was to develop and evaluate the natural essential oil-containing nanofiber (NF) mat with enhanced antibacterial activity, regenerative, non-cytotoxic, and wound-healing potential. Clove essential oil (CEO) encapsulated in chitosan and poly-ethylene oxide (PEO) polymers to form NFs and their morphology was analyzed using scanning electron microscopy (SEM) that confirmed the finest NFs prepared with a diameter of 154 ± 35 nm. The successful incorporation of CEO was characterized by Fourier transform infra-red spectroscopy (FTIR) and X-ray diffractometry (XRD). The 87.6 ± 13.1% encapsulation efficiency and 8.9 ± 0.98% loading of CEO was observed. A total of 79% release of CEO was observed in acidic pH 5.5 with 117% high degree of swelling. The prepared NF mat showed good antibacterial activity against Staphylococcus aureus and Escherichia coli and non-cytotoxic behavior against human fibroblast cell lines and showed good wound-healing potential.

4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects.

Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), ß-sitosterol (6), and ß-sitosterol ß-D-glucopyranoside (7). Their structures were elucidated using 1D (1H and 13C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with Ki of 5.39 µM and Ki' of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC50-values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC50 = 20.2 µM), breast cancer (MCF7, IC50 = 23.7 µM), and thyroid carcinoma (SW1736, IC50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC50 > 30 µM).

Enhancement of Oral Bioavailability of Ibandronate Through Gastroretentive Raft Forming Drug Delivery System: In Vitro and In Vivo Evaluation.

BACKGROUND: Bisphosphonates have very low bioavailability and cause irritation of the esophagus and stomach. This study was planned to improve the oral bioavailability of ibandronate through the formation of a raft in the stomach. Bisphosphonate-induced irritation of the esophagus and stomach is prevented by the formation of a raft. MATERIALS AND METHODS: The nanostructured raft was developed through the use of nanosized citrus pectin (NCP). The particle size of NCP was measured by zeta sizer and SEM. The percentage of NCP and the neutralization profile of raft was studied. The ibandronate, polymers, and the developed formulation were characterized by FTIR, XRD, TGA, and DSC. The release of ibandronate was studied in 0.1 N HCl, 0.5 N HCl, 1 N HCl, and simulated gastric fluid (SGF) and a cell viability study was performed using Caco-2 cells. The PPR5 formulation and Bonish 150 mg tablets were selected as test and reference formulations, respectively, for pharmacokinetic study. Twelve healthy albino rats were taken and divided into two groups using a Latin square crossover design, and the blood samples were collected for 24 hours. RESULTS: The SEM image showed that the particle size of NCP was 159 nm. The raft of PPR5 showed 94% NCP and 45 minutes duration of neutralization. The FTIR and XRD showed chemical stability and a uniform distribution of ibandronate in the raft. The TGA and DSC indicated the thermal stability of formulation. The release of 99.87% ibandronate at 20 minutes was observed in the SGF. The values of C max for the reference and test formulations were 493±0.237 ng/mL and 653±0.097 ng/mL, respectively. The AUC(0-t) of the reference and test formulations was 3708.25±3.418 ng/mL.h and 6899.25±3.467 ng/mL.h, respectively. CONCLUSION: The NCP has been successfully prepared from citrus pectin and has shown effective porous raft formation. The bioavailability of the ibandronate from newly developed PPR5 was higher than the already marketed formulation.

Cadmium Partitioning, Physiological and Oxidative Stress Responses in Marigold (Calendula calypso) Grown on Contaminated Soil: Implications for Phytoremediation.

Marigold (Calendula calypso) is a multipurpose ornamental plant, but its cadmium (Cd) tolerance and phytoremediation potential is unknown. The proposed study was carried out to unravel Cd partitioning, physiological and oxidative stress responses of C. calypso grown under Cd stress. Plants were grown for four months in pots having different soil Cd levels: 0, 25, 50, 75, and 100 mg kg-1 soil. Plant growth, biomass, photosynthetic pigments, leaf water contents, stomatal conductance, and membrane stability index were not decreased at 25 mg kg-1 Cd. At higher levels of Cd stress, activities of antioxidant enzymes (SOD, APX, CAT, POD) increased to mitigate H2O2 and lipid peroxidation. Cadmium uptake in plants increased with increasing soil Cd levels, and roots accumulated a greater portion of Cd, followed by shoots and flowers, respectively. On the basis of Cd accumulation and its tolerance, it was determined that C. calypso can be successfully grown for phytostabilization of Cd contaminated soils.

Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing.

Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1-9 from L. shawii and 10-20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D (1H and 13C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 µM, followed by compounds 1-3, 7, and 12, which depicted IC50 values in the range of 35-60 µM, while 8, 6, and 9 also demonstrated IC50 values >72 µM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC50 = 14.4 µM), 12 (IC50 = 23.3), and 2 (IC50 = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 µM) activity followed by 14 (241 µM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs.

The management of diabetes mellitus-imperative role of natural products against dipeptidyl peptidase-4, α-glucosidase and sodium-dependent glucose co-transporter 2 (SGLT2).

Diabetes mellitus is a chronic metabolic disorder which is rapidly spreading worldwide. It is characterized by persistent elevated blood glucose level above normal values (hyperglycemia) due to defect in either insulin secretion or in insulin action or both of them. Currently approved oral synthetic antidiabetic drugs such as biguanides, thiazolidinediones, sulfonylureas, and meglitinides have shown undesirable side effects. Therefore, newer approaches and targets for the management of diabetes mellitus are highly desirable. Dipeptidyl peptidase-4 enzyme, α-glucosidase enzyme and sodium-dependent glucose co-transporter 2 (SGLT2) have been recognized as effective therapeutic targets for the management of diabetes mellitus while natural products are alternatives to oral synthetic hypoglycemic agents. During the last two decades, many researchers were working on the identification and the validation of plant-derived products for curing various diseases. Natural products do not only provide useful drugs in their own right but also provide templates for the development of more effective compounds for enhanced therapeutic potential. Herein, we advocated the vital role of natural products as source of new drugs by presenting promising inhibitors of dipeptidyle peptidase-4 enzyme, α-glucosidase enzyme and (SGLT2) obtained from different medicinal plants as potential candidates for drug development against diabetes mellitus. The structure-activity relationship (SAR) of these various inhibitors is also discussed.

Development and pharmacokinetic evaluation of alginate-pectin polymeric rafts forming tablets using box behnken design.

Raft is an emerging drug delivery system, which is suitable for controlled release drug delivery and targeting. The present study aimed to evaluate the physico-chemical properties of raft, in vitro release of pantoprazole sodium sesquihydrate and conduct bioavailability studies. Box behnken design was used with three independent and dependent variables. Independent variables were sodium alginate (X1), pectin (X2) and hydroxypropyl methyl cellulose K100M (X3) while dependent variables were percentage drug release at 2 (Y2), 4 (Y4) and 8 h (Y8). The developed rafts were evaluated by their physical and chemical properties. Fourier transform infrared spectroscopy and differential scanning calorimetry were used to study the chemical interaction and thermal behaviour of drug with polymers. Alginate and pectin contents of R9 formulation were 99.28% and 97.29%, respectively, and acid neutralization capacity was 8.0. R9 formulation showed longer duration of neutralization and nature of raft was absorbent. The raft of R9 formulation showed 98.94% release of PSS at 8 h in simulated gastric fluid. Fourier transform infrared spectroscopy showed no chemical interaction and differential scanning calorimetry indicated endothermic peaks at 250 °C for pantoprazole sodium sesquihydrate. tmax for the test and reference formulations were 8 ± 2.345 h and 8 ± 2.305 h, respectively. Cmax of test and reference formulations were 46.026 ± 0.567 µg/mL and 43.026 ± 0.567 µg/mL, respectively. AUC(0-t) of the test and reference formulations were 472.115 ± 3.467 µg × h/mL and 456.105 ± 2.017 µg × h/mL, respectively. Raft forming system successfully delivered the drug in controlled manner and improved the bioavailability of drugs.

Cytotoxic, embryotoxic, insecticidal and anti-microbial activities of standardized Areca catechu nut.

The study was aimed at evaluating various biological actions of widely consumed Areca catechu nut. The nut's ethanolic extract exhibited cytotoxicity (lung cancer cell line), embryotoxicity (chick embryo), phytotoxicity (Lemna minor), insecticidal (Rhyzopertha dominica), anti-bacterial (Pseudomonas aeruginosa), anti-fungal (Microsporum canis) and mitogenic (human blood lymphocytes) actions. The standardization results revealed presence of 1.7 µ g arecoline per mg of extract. In conclusion, the Areca nut is endowed with both harmful and beneficial biological actions. Keeping in view its wide consumption and ease of availability, the aforesaid information should be channelized for health and agricultural benefits.

Therapeutic potential of glycyrrhetinic acids: a patent review (2010-2017).

INTRODUCTION: Glycyrrhetinic acids (GAs) viz., 18ß-glycyrrhetinic acid and 18α-glycyrrhetinic acid, are oleanane-type triterpenes having a carboxylic acid group at C-30, and are extracted from the Chines herbal medicine licorice (Glycyrrhiza uralensis). Although the pharmacological properties of GAs have long been known, attention to them has greatly increased in recent times due to their cytotoxic activity. AREAS COVERED: This review represents the patents granted about natural and synthetic glycyrrhetinic acid analogs from January 2010 to December 2017, the advances made by research groups in conjunction with pharmaceutical companies in the discovery of new natural or synthetic glycyrrhetinic acid analogs. EXPERT OPINION: GAs demonstrate excellent cytotoxic, antimicrobial, enzyme inhibitory, antiinflammatory, antioxidant, analgesic, and antiviral effects. It is interesting to note that the C-3(OH) and C30-CO2H functional groups make GAs very attractive lead structures for medicinal scientists since these functionalities allow the generation of further chemical diversity for improved pharmacological effects. Moreover, various GA analogues have been prepared via modification of the C30-CO2H. It is noteworthy that the C-30 amide of GA demonstrated better cytotoxic effects compared to the parent compounds. In addition, GAs have the capability to conjugate with other anticancer drugs or be converted into their halo or amino analogs which is expected to stimulate medicinal chemist to synthesize new lead compounds in cancer drug discovery.

Controlling Aedes albopictus and Culex pipiens pallens using silver nanoparticles synthesized from aqueous extract of Cassia fistula fruit pulp and its mode of action.

Mosquitoes act as key vector for transmission of devastating parasites and pathogens which affect millions of people globally. In this research, the green synthesis of silver nanoparticles of Cassia fistula fruit pulp as an innovative and operative tool against vector mosquitoes is presented. Silver nanoparticles were characterized by a series of techniques including Fourier transform infrared spectroscopy, Transmission Electron Microscope and confirmed by Scanning Electron Microscope, UV-Vis spectrophotometry and X-ray diffraction. Silver nanoparticles were highly effective against the larvae (I-IV instar) and pupae of Aedes albopictus and Culex pipiens pallens after 24, 48 and 72 h of treatment. Ae. albopictus had LC50 values ranging from 8.3 mg/L (I instar) to 17.3 mg/L (pupae) and LC50 ranging from 1.1 mg/L (I instar) to 19.0 mg/L (pupae) against Cx. pipiens pallens. The systemic effect of AgNPs was further assessed in the fourth instar larvae of Ae. albopictus and Cx. pipiens pallens by measuring the levels of total proteins and activity of two important marker enzymes: Acetylcholinesterase and α- and ß-carboxylesterase. Overall, the findings of the study suggest that the use of Cassia fistula-fruit pulp extract mediated synthesis of silver nanoparticles can be used for controlling vector mosquitoes. This is the first report on the mosquito larvicidal and pupicidal activity of AgNPs synthesized by Cassia fistula fruit pulp and its possible mechanism of action.

Acyl selenoureido benzensulfonamides show potent inhibitory activity against carbonic anhydrases from the pathogenic bacterium Vibrio cholerae.

A series of acyl selenoureido benzensulfonamides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against two Vibrio cholerae such enzymes (VchCAα over VchCAß) belonging to the α- and ß-classes, potential novel targets for anti-infective drugs development. These compounds showed strong inhibitory action against VchCAα over VchCAß and excellent selectivity over the human (h) off-target isoforms hCA I and II. Identification of potent and possibly selective inhibitors of VchCAα and/or VchCAß over the human counterparts may lead to pharmacological tools useful for understanding the physiological role(s) of these under-investigated proteins, possibly involved in the virulence of the bacterium and colonization of the host in bicarbonate rich regions of the gastro-intestinal tract.

Gamma-linolenic acid ameliorated glycation-induced memory impairment in rats.

CONTEXT: γ-Linolenic acid (GLA) is an important constituent of anti-ageing supplements. OBJECTIVE: The current study investigates the anti-ageing effect of GLA in Sprague-Dawley rats. MATERIALS AND METHODS: GLA (0.1, 0.2, 0.4, 2, 10, 20 and 24 µM) was initially evaluated for its effect on the formation of advanced glycation end products (AGEs) in vitro. For in vivo assessment (1, 5 or 15 mg/kg), the rat model of accelerated ageing was developed using d-fructose (1000 mg/kg (i.p.) plus 10% in drinking water for 40 days). Morris water maze was used to evaluate impairment in learning and memory. The blood of treated animals was used to measure glycosylated haemoglobin (HbA1c) levels. The interaction of GLA with active residues of receptor of AGE (RAGE) was analyzed using AutoDock Vina. RESULTS: Our data showed that GLA inhibited the production of AGEs (IC50 = 1.12 ± 0.05 µM). However, this effect was more significant at lower tested doses. A similar pattern was also observed in in vivo experiments, where the effect of fructose was reversed by GLA only at lowest tested dose of 1 mg/kg. The HbA1c levels also revealed significant reduction at lower doses (1 and 5 mg/kg). The in silico data exhibited promising interaction of GLA with active residues (Try72, Arg77 and Gln67) of RAGE. CONCLUSION: The GLA, at lower doses, possesses therapeutic potential against glycation-induced memory decline.

Pharmacological screening of Hypericum androsaemum extracts for antioxidant, anti-lipid peroxidation, antiglycation and cytotoxicity activity.

Oxidative stress and glycation processes have a combined effect on diabetes related complications. Crude plant extracts and plant derived compounds possessing both antiglycation and antioxidant activities have a high therapeutic potential for treating these complications. Antioxidant, antiglycation, anti-lipid per oxidation and cytotoxic activities of crude methanol extract and solvent fractions of Hypericum androsaemum L. (Hypericaceae) were evaluated and correlated with total content of phenolics and flavonoids. Significant radical scavenging activity was observed for the methanol extract against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical used as a basis for antioxidant activity with IC50 value of 92.70±2.85 µg mL(-1) (96.20±2.34% inhibition at 500 µg mL(-1)). In case of anion scavenging activity the results were not very significant (33.20±1.22% inhibition at 500 µg mL(-1)). Anti-lipid per oxidation activity was highest for n-hexane fraction (67.83±1.33% inhibition at 500 µg mL(-1)) while the ethyl acetate fraction had the highest antiglycation activity (62.77±2.54% inhibition at 500 µg mL(-1)). Statistically significant correlation was determined for antioxidant and antiglycation activity and phenolic and flavonoid contents. In cytotoxicity assay all the extracts had IC50 values >30 µg mL(-1) as compared to the standard cycloheximide (IC50 value 0.084±0.1 µg mL(-1)). The polar extracts of H. androsaemum can be a good source of non-toxic compounds with antioxidant, anti-lipid per oxidation and antiglycation activities.