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Featured researches published by Neelam Balekar.
Asian pacific Journal of Tropical Biomedicine | 2012
Sachin Jain; Dinesh Kumar Jain; Neelam Balekar
Abstract Objective To evaluate the in–vivo antioxidant potential of ethanolic extract of Mentha Pulegium against CCl4 induced toxicity in rats. Methods Animals were treated with plant extract for 7 days and then toxicity was induced with a single CCl4 intraperitoneal injection. Pre–treatment with 600 mg/kg (p.o.) of ethanolic extract of Mentha Pulegium improved the glutathione, SOD, catalase, and peroxidase levels significantly as compared to control group. Results The present studies revealed that Mentha Pulegium has significant in–vivo antioxidant activity and can be used to protect tissue from oxidative stress. The result showed that the activities of glutathione, SOD, catalase and peroxidase in group treated with CCl4 declined significantly than that of normal group. Conclusion Ethanolic extract of Mentha Pulegium in the dose of 600 mg/kg, p.o., has improved the glutathione, SOD, catalase, and peroxidase levels significantly, which were comparable with Liv 52. Based on this study we conclude that Ethanolic extract of Mentha Pulegium possesses in vivo antioxidant activity and can be employed in protecting tissue from oxidative stress.
Chinese Journal of Natural Medicines | 2014
Mithun Singh Rajput; Neelam Balekar; Dinesh Kumar Jain
AIM The fruits of Lagenaria siceraria (Molina) Standl. (Cucurbitaceae), a commonly used vegetable, are reported to possess various medicinal properties. In previous studies, the fibrinolytic potential of an ethanolic extract of fruits of Lagenaria siceraria was investigated in comparison with kaempferol isolated from it. The aim of the present study was to explore its mechanistic antithrombotic potential and antiplatelet activity using a wide dose range in different in vitro and in vivo models, and to quantify the total phenolic, flavonoid, and kaempferol contents using a colorimetric method. METHOD The antithrombotic potential was investigated using tail bleeding time in mice, a plasma recalcification assay, and pulmonary thromboembolism in mice. The antiplatelet activity was studied using an in vitro model to investigate IC50 value. RESULTS A significant amount of total phenols, flavonoids, and kaempferol was quantified in L. siceraria ethanolic extract. An ethanolic extract of the fruits of L. siceraria showed a significant increase in tail bleeding time and plasma recalcification time, significant protection against ADP induced pulmonary thromboembolism in mice, and also inhibited the platelet aggregation induced by ADP in vitro. The study suggested that the fruits of L. siceraria exhibit significant antithrombotic potential due to inhibition of ADP-mediated platelet aggregation and the involvement of various non-cellular chemical mediators of blood. CONCLUSION This finding may be helpful in treating the serious consequences of the thrombus formed in blood vessels which include atherothrombotic diseases, such as myocardial or cerebral infarction. So, further investigation should be done for revealing exact mechanism of action behind these types of activities.
Natural Product Research | 2010
Sachin Jain; Avijeet Jain; Neetesh Jain; Devendra K Jain; Neelam Balekar
We evaluate the in vitro free radical scavenging activity of the leaves of Tabernaemontana divaricata Linn. Petroleum ether, ethanol and aqueous extracts of T. divaricata were prepared with successive extraction in a soxhlet apparatus. Each extract was selected to study the free radical scavenging activity by superoxide scavenging assay method. It was found that the aqueous extract contained carbohydrates, glycosides, amino acids, flavonoids, tannins, alkaloids, and steroids, and the ethanolic extract contained glycosides, amino acids, flavonoids, tannins, alkaloids and steroids. The ethanolic extract of T. divaricata showed 58.7 ± 0.62% inhibition in the superoxide scavenging model. The aqueous extract also showed almost similar activity (54.9 ± 0.53% compared to the ethanolic extract), while petroleum ether extract showed poor inhibition of superoxide scavenging activity. All extracts showed the dose- and time-dependent inhibition of the superoxide scavenging activity.
Journal of acute disease | 2014
Mithun Singh Rajput; Neelam Balekar; Dinesh Kumar Jain
Abstract Objective To investigate the antiatherosclerotic potential of Lagenaria siceraria (L. siceraria) by calculating percentage plaque area in aorta and grade of atheromatous lesions modulated by HMG–CoA reductase enzyme and lipoprotein lipase enzymes levels in hyperlipidemic rats. Methods Rats were divided into different groups, fed with high cholesterol atherogenic diet and in addition supplemented with ethanolic extract of fruits of L. siceraria and standard drug atorvastatin. At the end of the treatment schedule, the atherosclerotic lesion area was measured in cross-sections of the aortic root and grading of atherosclerotic lesions was done. The blood samples from animals of different groups were evaluated for serum lipid profile determination and plasma lipoprotein lipase activity and the hepatic HMG-CoA activity was also determined. Results Treatment of rats with ethanolic extract of fruits of L. siceraria significantly lowers the risk of atherosclerosis by lowering percentage plaque area in aorta and grade of atheromatous lesions in hypercholesterolemic rats and also serum cholesterol, triglyceride, LDL–c, VLDL–c and increased HDL–c levels as well. The extract also induced lipoprotein lipase activity and significantly decreased cholesterogenesis in liver by reducing HMG-CoA reductase activity in hypercholeaterolemic rats. Conclusion It can be concluded that ethanolic extract of fruits of L. siceraria contains active components which ameliorates the atheromatous lesions in rat aorta and lowers the risk of atherosclerosis in hypercholesterolemic rats.
Asian Pacific Journal of Tropical Disease | 2012
Sachin Jain; Dinesh Kumar Jain; Neelam Balekar; Ankit Jain
Abstract Objective To study the antifertility activity of Tabernaemontana divaricata leaf extract on female albino mice. Methods Animals were divided into three groups consisting of five animals in each group. One group served as control and received vehicle orally for 21 days. The other two groups received dried ethanolic extract of leaves orally at a dose of 250 and 450 mg/kg animal body weight per day. After 21 days of treatment, extract was withdrawn from the mice and estrous cycle was studied for another 21 days. Results The results of this study revealed that treatment of mice with extract of 250 and 450 mg/kg body weight for 21 days caused a prolonged eastrous cycle with significant increase in the duration of diestrus phase and elongation of estrus stage in treatment with higher dose (450 mg/kg body weight) and simultaneously decrease in the luteinizing hormone (LH) in both the treated groups and follicle stimulating hormone (FSH) in higher dose of treatment compared to the control animals may indicate the disturbance of estrous cycle and ovulation through suppression of FSH. Conclusions It concludes that disturbance on the estradiol secretion with significant decrease during estrous stage of the cycle observed with the extract treatment may be due to impairment of LH and FSH.
Journal of Drug Delivery and Therapeutics | 2017
Praveen Kumar Sharma; Sachin Jain; Neelam Balekar
Diarrhea is one of the most general causes for thousands of deaths each year. Consequently, identification of new source of antidiarrheal drugs becomes one of the most prominent focuses in modern research. Our aim was to investigate the antidiarrheal activity of methanolic extract of Daemia extensa R. Br. (MEDE) leaves in rats. Antidiarrheal effect was evaluated by using castor oil-induced diarrhea at 200 mg/kg and 400 mg/kg body weight in rats where the extract showed considerable antidiarrheal effect by inhibiting 49.47% and 62.85% of diarrheal period at the doses of 200 and 400mg/kg, correspondingly These observed effects are comparable to that of standard drug loperamide (5mg/kg). So these results indicate that bioactive compounds are present in methanolic extract of Daemia extensa leaves including significant anti-diarrheal activity and could be accounted for pharmacological effects.
Archive | 2015
Neelam Balekar; Dinesh Kumar Jain
T review focuses on ethnopharmacological uses of Peucedanum species, as well as the phytochemical, pharmacological and toxicological studies on this genus. Through this review, I intend to highlight the known and potential effects of the Peucedanum species or their isolated compounds and show which of traditional medicine uses have supported by pharmacological investigations. Several bioactive substances, including coumarins, polyphenols, flavonoids, phenolic acids, essential oils, diterpenes and other components, have been isolated from species of Peucedanum. Coumarins and essential oils are considered the main components of almost all Peucedanum plants and can be responsible for many of their biological and pharmacological activities of Peucedanum species such as anti-inflammatory, antidiabetic, anti-platelet aggregation, and antiproliferative activities, cardiopulmonary protection, neuroprotection and phototoxicity. Moreover, because the botanical classification of Peucedanum species by anatomical and morphological features is difficult, chemicals of essential oils and coumarins have been valuable as chemotaxonomic markers. In this review, I explain the importance of some coumarins, such as praeruptorins A and B, for preventing or treating cancer, cardiovascular problems and some inflammatory diseases. In conclusion, some Peucedanum species have emerged as a good source of the traditional medicine for treatment of inflammation, microbial infections and cardiopulmonary diseases and provides new insights for further investigations on isolated compounds specially on praeruptorins to find novel therapeutics and drug discovery. However, for uses of Peucedanum species to prevent and treat various diseases, the additional pharmacological studies to find the mechanism of action, safety and efficacy of them before starting clinical trials are required.H is a 24-amino acid peptide known for its anti-apoptotic activity, especially against neuronal cell death caused by Alzheimer insults. Herein, we show a novel function of humanin and its derivatives, namely protection against necrosis, demonstrated both in vitro and in vivo. The synthesis of humanin is difficult due to the involvement of the hydrophobic amino acids that impose aggregation on the resin. Solid-phase peptide synthesis of humanin and its three derivatives, AGA-HNG, HNG and HN17 gave low yields. In order to avoid aggregation and overcome difficult sequences couplings, we developed efficient synthetic procedures that are based on fragment condensation in solution. Furthermore, native chemical ligation was applied to overcome resin aggregation for synthesis of peptides that contain cysteine. We found that humanin and its derivatives conferred protection in PC-12 and NSC34 cell lines in which necrosis was induced in glucose-free medium by either chemohypoxia or upon staurosporine/oligomycin-A treatment. Moreover, in vivo protective effect was shown in traumatic brain injury model in mice, where necrosis is the main mode of the neuronal cell death. We show that humanin derivatives antagonize the decrease in ATP levels associated with necrosis and also directly enhance the activity of isolated ATP synthase complex, indicating that humanin derivatives target the mitochondria, regulating ATP levels. The present findings could provide new therapeutic protocols for treatment of brain ischemic states, such as stroke, and traumatic brain injury, conditions for which no efficient drug-based treatment is currently available.Methods: Diabetes was induced in adult male Wister rats by administration of (Streptozotocin; STZ) at a dose of 52.5 mg/kg, i.p. Animals with diabetes were treated with either Ah ethanolic extract or gliclazide (10mg/kg, p.o.) for 14 days. Biochemical analysis was done such as glucose, insulin, homocysteine, lipid profile (cholesterol, triglyceride), liver function tests (T.bilirubin, AST and ALT), kidney function tests (BUN, sr. creatinine) and oxidative stress biomarkers. In addition, pancreas, liver, kidney, heart and aorta tissues were dissected out for pathological examination. Immuno histochemical study was done on pancreatic tissues for determination of insulin and glucagon immune reactivities. Liver tissues were also separated for genetic analysis.T objective of our present research was to identify the novel therapeutic target for diabetic cardiomyopathy. To achieve this level of identifications we try to inspect the genes related to metabolism and its crucial title role in the cardiac functions during diabetes. In this study, via microarray analysis we observed the significant rises of metabolic gene expression such as acyl-CoA thioesterase 1 level in the myocardia of db/db mice when compared to normal group of animals. Consequently, gain-of-function and loss-of-function approaches in db/db mice were studied via acyl-CoA thioesterase 1 gene expression level in cardiac functions. Present investigations also exemplify the significant anti-diabetic potential of ginseng total saponin (GTS). Though, the multifaceted connection between the anti-diabetic effects of Korean Red Ginseng (KRG) and its sound effects on the level of metabolic gene expression on anti-diabetic animal’s heart has not identified. Henceforth, in current research, we attempt to assess the link between the anti-diabetic effects of KRG and the level of metabolic gene expression profiles in the heart of db/db mice. Apoptosis-related genes including Cideb, Bdnf, Myc, Cd74, Inhbb, Lcn2, Cyfip2, Aen, Prune2, Spp1, Gadd45b, and Sphk1 were significantly reduced along with considerable increases of the levels of Gas1, Angptl4, Fn1, Tpx2, Egfr, Snai2, Sfrp2, Gas1, and Lpar1 genes after KRG treatment. Above indicated interesting outputs elucidated that the genes in charge for apoptosis and inflammation processes were downregulated at significant manner by KRG treatment. From these observations, we can conclude that the KRG treatment potentially defending diabetes correlated cardiac problems at the level of its genome.N compounds isolated from Ginseng have been shown to exhibit various biological activities, including antioxidant, anticarcinogenic, anti-mutagenic, and anti-tumor activities. Recent research has focused on the potential values of these compounds in the prevention and treatment of human cancers. The anti-tumor activity of 25-hydroxyprotopanaxadiol (25-OH-PPD), a natural compound isolated from Panax ginseng, has been established in previous study. In the current study, we investigated the anti-tumor activity of three derivatives of 25-OH-PPD, namely xl, 1c, and 8b with respect to lung cancer. All three compounds significantly inhibited the growth of the human lung cancer cells A549 and H460. Oral administration of these compounds significantly inhibited the growth of xenograft tumors in mice without affecting body weight. Further mechanistic study demonstrated that these compounds could decrease the expression levels of β-catenin and its downstream targets Cyclin D1, CDK4, and c-myc in lung cancer cells. Taken together, the results suggested that the anti-growth activity exerted by these 25-OH-PPD derivatives against lung cancer cells probably involved β-catenin-mediated signaling pathway, a finding that could have important implication for chemotherapeutic strategy aiming at the treatment of lung cancer.A sessiliflorus, is a smaller woody shrub and has traditionally been referred to have anticancer activity, but it has not been scientifically explored so far. Therefore, the present study was aimed to elucidate the anticancer effect of Acanthopanax sessiliflorus stem bark extracts (ASSBE). The stem barks was extracted in methanol and then fractionated with hexane, butanol and water. Cytotoxicity of these fractions against MDA-MB-231 and MCF-7 human breast cancer cells was determined by MTT colorimetric assay. The hexane fraction of ASSBE showed greater activity towards both the human breast cancer cells compared to other two fractions at a minimal concentration of 50 μg/ml. Hence, we were further investigated the effects of this bioactive fraction, n-hexane (ASSBE-nHF) on breast cancer cells. ASSBE-nHF significantly reduced the proliferation of breast cancer cells assessed by counting cell numbers after 72 h treatment using hemocytometer. The Annexin V-FITC/PI, Hoechst 33342 staining, DNA fragmentation assays and immunoblotting of apoptosis markers like caspases showed ASSBE-nHF induces necrosis like cell death in MCF-7 and MDA-MB-231 cells. Further, ASSBE-nHF significantly increased the production of ROS and decreased the mitochondrial membrane potential (MMP) in MCF-7 cells. Similarly, it decreased the MMP in MDA-MB-231 cells, but had no effect on ROS production. The cytotoxic effect of ASSBE-nHF in MCF-7 cells was not significantly reversed even in the presence of n-acetylcysteine, an antioxidant. Moreover, ASSBE-nHF significantly decreased the levels of caspase 3, caspase 7, caspase 9, caspase 8, cyclin D1 and including the house keeping protein GAPDH represents the inhibition of protein synthesis in human breast cancer cells. Since, necrotic dying cells retain the process of protein synthesis, Acanthopanax sessiliflorus stem bark extracts induced cytotoxic effects in human breast cancer cells might be through endoplasmic reticulum stress response. In conclusion, the present findings provide evidence that ASSBE-nHF induces non-apoptotic cell death in human breast cancer cells via both ROS dependent and independent pathways associated with mitochondrial membrane depolarization.C a member of the CC-chemokine sub-family, plays an important role in recruiting leukocytes to inflammatory sites. Studies have suggested that CCL2 and its major receptor CCR2 are associated with a variety of neurological disorders. However, emerging evidence indicates that CCL2 exerts neuromodulatory actions and plays a neuroprotective role in certain injuries and insults, although the underlying mechanism remains elusive. The present study investigated the neuroprotective effects of CCL2 against excitotoxic insult and elucidated the intracellular signaling cascades triggered by this chemokine using primary cultured rat cortical neuronal cells as a model. CCL2 alone had no effect on viability and caspase 3 activity of the cultured cells under the prevailed experimental conditions. Rather, it significantly attenuated excitotoxic neuronal damage as well as reactive oxygen species production induced by N-methyl-D-aspartate (NMDA) or L-glutamate, and inhibited the NMDA-induced activation of caspase 3. CCL2 induced phosphorylation of MEK1/2, extracellular regulated kinase (ERK)1/2, p90RSK, and Akt in concentrationand timedependent manners. CCL2-induced activations of ERK1/2 and p90RSK were inhibited by U0126, a MEK1/2 inhibitor, suggesting that CCL2-triggered activation of p90RSK is mediated through the MEK/ERK signaling pathway. CCL2-induced phosphorylations of Akt, ERK1/2, and p90RSK were inhibited by the broad spectrum PI3K inhibitors wortmannin and LY294002, as well as the PI3Kγ inhibitor AS605240, suggesting that these three kinases are downstream modulators of PI3Kγ in the CCL2 signaling pathway. Taken together, these findings contribute to the understanding of the neuroprotective role of CCL2 and its signaling pathways in the brain where PI3Kγ plays a vital role.Objective: Beta-blockers are a heterogeneous class of agents that are used in the treatment of many cardiovascular diseases, especially hypertension and atherosclerosis, and that are commonly prescribed after cardiac surgery. In the present study, the aim is to investigate the vasorelaxant effects of some common beta-adrenoceptor blockers on the human radial artery in vitro, as well as their relaxation mechanisms. Methods: Radial artery rings sourced from human patients were mounted in an organ bath and tested for changes in isometric tension in relaxation response to labetalol, nebivolol, and propranolol in the presence and absence of NG-nitro-L-arginine methyl ester (3310 � 5 mol/L) and tetraethyl ammonium (3310 � 4 mol/L). Results: The labetalol (10 � 8 to 10 � 4 mol/L), nebivolol (10 � 8 to 10 � 4 mol/L), and propranolol (10 � 8 to 10 � 4 mol/L) induced concentration-dependent relaxations on the radial artery rings, which had been precontracted with phenylephrine (10 � 6 mol/L). The relaxation response induced by labetalol in the isolated radial artery rings was significantly higher when compared with the nebivolol and propranolol samples (P < .05). NG-nitro-L-arginine methyl ester significantly reduced the relaxation of nebivolol (P <.05), and tetraethyl ammonium significantly reduced the relaxation of labetalol, nebivolol, and propranolol (P<.05). Conclusions:We speculatedthat therelaxanteffectof labetalol,nebivolol,and propranololwas due partly tothe Ca 2þ -activated K þ channels. In addition, the relaxation induced by nebivolol was largely related with nitric oxide release. Nebivolol, and partly propranolol, may provide significant therapeutic benefit, but labetalol can be a good alternative for coronary artery bypass grafting with radial artery use. (J Thorac Cardiovasc Surg 2015;149:1036-40)O of the methods used to determine water content is Karl-Fischer titration. The aim of this work was to determine the water content of particular matrix tablet’s layer after hydration by Karl-Fischer method. The tablets contained sodium alginate. In order to prepare the samples, a special device (that allow hydrating and subsequent cutting the layers) has been invented. The device contains a holder (to place a tablet) and a micrometric screw wchich allows moving up the tablet in the holder to the reguired height. The device with a tablet inside is placed in a beaker filled with water heated up to 37°C . After reaching a required timepoint (1; 2; 3 or 4 hours), the device is removed from the beaker. Each layer is cut with a spatula (slice of 1 mm) and weighted on analytical weight. After cutting a layer, a tablet is moved 1 mm up with a micrometric screw. In such a way 5 layers (of 1 mm each) are obtained. The samples are put into flasks and filled with metanol.Water content of the samples is determined by Karl-Fischer method. The results show the water migrates into the lower parts of the tablet during hydration, as it was detected both in external and internal layers at each timepoint. What is more, water content decreases according to the distance from the tablet surface. Additionally, each layer (besides the external one) gets more water upon longer hydration. The presented method is the first that allows determination of water content in any layer of the hydrated matrix tablet.O lyophilisates are solid preparations intended either to be placed in the mouth or to be dispersed (or dissolved) in water before administration. They are obtained by freeze-drying (lyophilisation), involving division into single doses, freezing, sublimation and drying of usually aqueous, liquid or semi-solid preparations. They combine the advantages of both solid and liquid forms, particularly useful in the case of patients with dysphagia. The presence of metastable state and the glass transition temperature (Tg) are two important aspects when formulating a freeze drying product. Therefore, thermal analysis studies (differential scanning calorimetry, DSC) were performed in order to determine Tg for each excipient separately, the active substance used as model and also the combinations among them. We have studied two common excipients used in freeze drying formulations: the saccharide mannitol (MNT) in concentrations from 2-7% and the water-soluble polymer polyvynilpirrolidone (PVP)-in concentrations from 1-5%. Only MNT presented metastable state. Three out of nine formulas studied (with the active substance) did not presented metastable state, with a Tg ranging from -27 to -32oC. It was also seen that increasing the concentration of PVP resulted in a slight decreased of Tg.correspondence: sahar Mohamed Kamal Department of Pharmacology, Faculty of Medicine, Ain shams University, cairo, Egypt Tel +202 2418 6992 Fax +202 2418 6992 Email [email protected] Background: Accurate timing of statin administration is considered important to obtain the best hypolipidemic effect. Pravastatin is one of the currently prescribed hepatic 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors, and was chosen in this study to evaluate its antioxidant effect when administered as a single daily dose in the morning versus evening in cholesterol-fed rabbits. Methods: This 12-week study was performed in New Zealand rabbits, divided into four groups (n = 6 each), ie, normocholesterolemic controls; cholesterol 1% diet, nontreated ; cholesterol 1% diet treated with pravastatin in the morning; and cholesterol 1% diet treated with pravastatin in the evening. Plasma total cholesterol levels, superoxide dismutase enzyme levels in erythrocyte lysates, thiobarbituric acid-reactive substance content, catalase, and glutathione enzyme activity in liver homogenates from the tested rabbits were measured. Results: Both morning and evening treatment with pravastatin significantly improved all the measured antioxidant markers in comparison with nontreated cholesterol-fed rabbits. However, results obtained with evening dosing were better than with morning dosing. Conclusion: The antioxidant profile of pravastatin is better when the drug is administered in the evening rather than in the morning.Methods: A descriptive cross-sectional study was conducted among adults 18 years and above in Petaling district, Malaysia. Subjects were interviewed based on a validated questionnaire to elicit information on socio-demographic data, prevalence and level of awareness on skin infection. Whereas the impact of skin infection on quality of life was questioned using a validated questionnaire Dermatology Life Quality Index (DLQI). Data was analyzed using Microsoft Excel and SPSS version 18.0.I Latin America, the implementation of bioequivalence (BE) studies is still unequal. There are remarkable advances, as well as there are some countries without regulations in this field. Despite of this heterogeneity it is possible to recognize efforts from the National Regulatory Agencies (NRA) in discussing bioequivalence criteria, biowaivers based on the concept of the Biopharmaceutical Classification System (BCS), therapeutical equivalence, and interchangeability issues. With this background, regulations have emerged based on in vitro and in vivo assays, but there are differences in terms of the assessment criteria and time elapsed from the application to final approval. However, since the emergence of the BCS there has been an interesting discussion regarding the possibility of including biowaivers in some cases. There is a consensus to apply a biowaiver study for solid oral dosage forms containing an active principle ingredient belonging to Class 1 of BCS (high solubility and high permeability), excluding drugs with narrow therapeutic index, but the interpretation of how to apply biowaivers based on other BCS classes differs between regulatory authorities. Considering that, the pharmaceutical market can reach USD 1,200 billion by 2016, it seems that is necessary to conciliate innovation and implementation of generic drugs. Furthermore, this implementation should be based on the best BE and biowaiver practices and criteria to improve access to safe and effective medicines at reasonable costs.P aeruginosa is a pathogen commonly present in the lungs of patients with chronic airway infection in cystic fibrosis (CF). Pseudomonas aeruginosa produces proteins called proteases that are associated with virulence and disease progression. These proteases were recently shown to recognize and specifically cleave peptides comprising three glycines (3xGly). We believe that this feature can be used to facilitate the specific site-specific delivery of theraupetic agents to the lungs of CF patients. More specifically, nanoparticles capped with 3xGly peptides will release the loaded content only upon proteolytic activity of P. aeruginosa present in the lungs thus providing site specific release of the drug. Furthermore, we have studied the potential of nanoparticles for delivery of antibacterials to gram-negatives to eradicate P. aeruginosa infection in in vitro models for host-pathogen interactions in the lungs.D Acid (DOCA) and 3-Aminomethyl Phenylboronic Acid (AMPB)-conjugated self-assembled Nanoparticles (NPs) of Chondroitin Sulfate A (CSA) were prepared for tumor targeting and penetration. The hydrophobic DOCA derivative was conjugated to the hydrophilic chondroitin sulfate A (CSA) backbone, followed by conjugation of AMPB to CSA-DOCA. Loading doxorubicin (DOX) to these CSA-DOCA and CSA-DOCA-AMPB NPs resulted in NPs of around 230 nm mean diameter, narrow size distribution, negative zeta potential, and relatively high drug encapsulation efficiency (up to 85%). CSA-DOCA and CSADOCA-AMPB NPs exhibit improved in vitro cellular uptake and penetration as evidenced by confocal laser scanning microscopy and flow cytometry. In vivo tumor targeting and penetrating by these NPs, based on both CSA-CD44 receptor and boronic acidsialic acid interactions, was revealed using Near-Infrared Fluorescence (NIRF) imaging in the tumor-xenografted mouse mode. Both passive and active strategies seem to have contributed to the in vivo tumor targetability of the NPs. These NPs could be a promising theranostic nano-platform for cancer therapy and imaging.M Metalloproteinases (MMPs), have long been considered as potential biomarkers in many types and stages of cancer. MMP-9 (gelatinase B), plays important role on extracellular matrix degradation and cell migration and it’s overexpressed in breast cancer resulting with tumor invasion. On the basis of the pivotal roles of MMPs, the pharmaceutical industry has been investigating potent MMP inhibitors for several years and some indole derivatives are known to have inhibitory effects on MMPs. The aim of this study is to evaluate the effects of newly synthesized indoline-2-thione derivatives on proliferation, apoptosis and MMP-9 mRNA expression of human MCF-7 breast adenocarcinoma cells. In this context, the effects of newly synthesized 3-(Substitue-benzylidene)-1,3-dihydro-indoline-2-thione derivatives [compounds 1-3] on cell growth, proliferation and apoptosis of human MCF-7 breast carcinoma cells were evaluated. Quantitative real-time reverse transcription PCR was performed to quantify the mRNA expression of MMP-9. The compounds [1-3] significantly inhibited cell growth with IC values of 0.296, 1.179 and 1.771 μM, respectively. Although the BrdU-treated cells demonstrated a statistically significant dose-responsive decrease in cell numbers for all compounds, compound [3] was the most potent anti-proliferative agent that the proliferating cell amount decreased to 38.40% when compared with control. The results also showed that compound [3] inhibited the expression of MMP-9 protein even at 10 μM concentration. In conclusion, the newly synthesized indole derivatives inhibited cell growth and proliferation of MCF-7 cells significantly. The results also showed that these compounds display their cytotoxic effects through inhibition of MMP-9 mRNA expression.G is a novel ginseng-derived Lysophosphatidic Acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer’s Disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using AD animal models. Gintonin induced [Ca2+]i transient in cultured mouse hippocampal Neural Progenitor Cells (NPCs). Gintonin-mediated [Ca2+]i transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin (25, 50, or 100 mg/kg.day for 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg for 2 weeks) also significantly attenuated Amyloid-β protein (Aβ)induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased Choline Acetyltransferase (ChAT) activity and immunoreactivity, and increased Acetylcholine Esterase (AChE) activity. In a transgenic AD mouse model, longterm oral administration of gintonin (25 or 50 mg/kg for 3 months) also attenuated AD-related cholinergic impairments, such as decreased acetylcholine concentration, decreased ChAT activity and immune-reactivity, and increased AChE activity. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to Aβ and could be utilized for AD prevention or therapy.Methods: A descriptive cross-sectional study was conducted among adults 18 years and above in Petaling district, Malaysia. Subjects were interviewed based on a validated questionnaire to elicit information on socio-demographic data, prevalence and level of awareness on skin infection. Whereas the impact of skin infection on quality of life was questioned using a validated questionnaire Dermatology Life Quality Index (DLQI). Data was analyzed using Microsoft Excel and SPSS version 18.0.N Fatty Liver Disease (NAFLD) has been recognized as the most common hepatic inflammatory disorders caused by an accumulation of fat deposits in the liver. COX-2 expression is related to the inflammatory phenomena in the early phases of chronic liver diseases and to the induction of hepato-carcinogenesis. The present study investigated the anti-inflammatory effects of a root extract of Cynanchum wilfordii in order to elucidate the molecular mechanisms of action of the protective properties on NAFLD. Mice were randomly divided into 6 groups with 6 mice in each group: (1) normal control chow diet plus vehicle (NC); (2) high-cholesterol diet with 10% fructose in the drinking water (HCD+FRU); (3) HCD+FRU plus 50 mg/kg.bw/day; (4) HCD+FRU plus 100 mg/kg.bw/day of CWE; (5) HCD+FRU plus 200 mg/kg.bw/ day of CWE or (6) HCD+FRU plus 10 mg/kg.bw/day of simvastatin via oral gavage for 12 weeks. Our results indicate that the severity of histological changes and lipid accumulation in the liver were decreased by CWE treatment. Moreover, GOT, GPT, and cholesterol levels showed significantly and dose-dependently reduced in the CWE treatment groups (50, 100, and 200 mg/ kg) compared with HCD. We observed a significant high expression of COX-2 in the liver of HCD group and administration of CWE significantly reduced the expression of COX-2. These results suggested that the root of C. wilfordii may be used for the prevention and treatment of non-alcoholic fatty liver disease.A allergy is a hypersensitivity disorder of the immune system. Arctium lappa L., known as a Burdock, is a popular edible vegetable but its anti-allergic potential remains unknown. In this study, the anti-allergic effect of A. lappa extracts was determined using Sprague-Dawley rats, ICR mice, and RBL-2H3 mast-like cells. Among fractions extracted with several solvents, EtOH fraction of A. lappa (ALE) at 100 μg/ml showed the maximal inhibitory effect on β-hexosaminidase release and the high cell viability in RBL-2H3 cells. Administration of ALE (100 mg/kg) highly suppressed the passive cutaneous anaphylaxis (PCA) induced by anti-DNP-specific IgE insult in rats, and attenuated the compound 48/80-induced systemic allergic reaction, anaphylaxis, and histamine release in mice. In order to identify the active compound from ALE with antiallergic action, we subsequently performed further fractionation with determining β-hexosaminidase assay in every subfractions and its main active component was identified as an oleamide. Oleamide attenuated the secretion of histamine and β-hexosaminidase, and the production of allergic-related cytokines such as IL-4 and TNF-α in RBL-2H3 cells treated with compound 48/80 or A23187/PMA. In addition, oleamide administration suppressed FceRI-tyrosine kinase Lyn-mediated pathway. The anti-allergic effect of ALE and its bioactive component oleamide may have beneficial effects in the treatment of human allergic diseases.
Archive | 2012
Neelam Balekar; Dinesh Kumar Jain; Pankaj Dixit; Veena Nair
Journal of Drug Delivery and Therapeutics | 2017
Aayushi Kavachale; Taru Shrivastava; Neelam Balekar
Archive | 2013
Neelam Balekar; Anil Kumar Pasi; Gaurav Parihar; Devendra K Jain