Commenced in January 2007
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Edition: International
Paper Count: 19

Search results for: nicotinamide

19 The Role of NAD+ and Nicotinamide (Vitamin B3) in Glaucoma: A Literature Review

Authors: James Pietris

Abstract:

Glaucoma is a collection of irreversible optic neuropathies which, if left untreated, lead to severe visual field loss. These diseases are a leading cause of blindness across the globe and are estimated to affect approximately 80 million people, particularly women and people of Asian descent.1This represents a major burden on healthcare systems worldwide. Recently, there has been increasing interest in the potential of nicotinamide (vitamin B3) as a novel option in the management of glaucoma. This review aims to analyse the currently available literature to determine whether there is evidence of an association between nicotinamide adenine dinucleotide (NAD+) and glaucomatous optic neuropathy and whether nicotinamide has the potential to prevent or reverse these effects. The literature showed a strong connection between reduced NAD+ levels and retinal ganglion cell dysfunction through multiple different studies. There is also evidence of the positive effect of nicotinamide supplementation on retinal ganglion cell function in models of mouse glaucoma and in a study involving humans. Based on the literature findings, a recommendation has been made that more research into the efficacy, appropriate dosing, and potential side effects of nicotinamide supplementation is needed before it can be definitively determined whether it is appropriate for widespread prophylactic and therapeutic use against glaucoma in humans.

Keywords: glaucoma, nicotinamide, vitamin B3, optic neuropathy

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18 Electro-oxidation of Catechol in the Presence of Nicotinamide at Different pH

Authors: M. A. Motin, M. A. Aziz, M. Hafiz Mia, M. A. Hasem

Abstract:

The redox behavior of catechol in the presence of nicotinamide as nucleophiles has been studied in aqueous solution with various pH values and different concentration of nicotinamide using cyclic voltammetry and differential pulse voltammetry. Cyclic voltammetry of catechol in buffer solution (3.00 < pH < 9.00) shows one anodic and corresponding cathodic peak which relates to the transformation of catechol to corresponding o-benzoquinone and vice versa within a quasi reversible two electron transfer process. Cyclic voltammogram of catechol in the presence of nicotinamide in buffer solution of pH 7, show one anodic peak in the first cycle of potential and on the reverse scan the corresponding cathodic peak slowly decreases and new peak is observed at less positive potential. In the second cycle of potential a new anodic peak is observed at less positive potential. This indicates that nicotinamide attached with catechol and formed adduct after first cycle of oxidation. The effect of pH of catechol in presence of nicotinamide was studied by varying pH from 3 to 11. The substitution reaction of catechol with nicotimamide is facilitated at pH 7. In buffer solution of higher pH (>9), the CV shows different pattern. The effect of concentration of nicotinamide was studied by 2mM to 100 mM. The maximum substitution reaction has been found for 50 mM of nicotinamide and of pH 7. The proportionality of the first scan anodic and cathodic peak currents with square root of scan rate suggests that the peak current of the species at each redox reaction is controlled by diffusion process. The current functions (1/v-1/2) of the anodic peak decreased with the increasing of scan rate demonstrated that the behavior of the substitution reaction is of ECE type.

Keywords: redox interaction, catechol, nicotinamide, substituion reaction, pH effect

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17 In Vitro and in Vivo Evaluation of Nano Collagen Molecules to Enhance Mesenchymal Stem Cells Differentiate into Insulin Producing Cells

Authors: Chin-Tsu Ma, Yi-Jhen Wu, Hsia Ying Cheng, Han Hsiang Huang, Shyh Ming Kuo

Abstract:

The use of specific molecules including nutrients and pharmacological agents has been tried in modulation of stem cells differentiation (MSCs) to insulin producing cells. The aim of this study is to investigate the ability of nano collagen molecules (nutrient or scaffold) to enhance the MSCs differentiation into insulin-producing cells in combination with nicotinamide and exendin-4 (pharmacological agents) in vitro and in vivo. The results demonstrated that the cells exhibit morphologically islet-like clusters after treatment with nano collagen molecules, nicotinamide and exendin-4. MSCs extra treated with nano collagen molecules showed significant increases in Nkx6.1 and insulin mRNA expression at 14-d and 21-d culture compared with those merely treated with nicotinamide and exendin-4. Early 7-day elevation in PDX-1 mRNA expression was observed. Furthermore, the MSCs exposed to nano collagen molecules produced the highest secretion of insulin (p < 0.05). Type-2 diabetes induced by high-fat diet and low dose of streptozotocin in rat model was built in this study. This rat exhibited higher food intake, water intake, lower glucose tolerance, lower-insulin tolerance, and higher HbA1C (significant increases, p < 0.01) as compared with the normal rat that demonstrated the model of type-2 diabetes was successfully built. Biopsy examinations also showed that obvious destruction of islet. After injection of differentiated MSCs into the destructed pancreas of diabetes rat, more regenerated islet were observed at the rats that treated with nano collagen molecules and exhibited much lower HbA1C as compared with the normal rat and diabetes rat after 4 weeks (significant deceases, p < 0.001). These results indicate that the culturing MSCs with nano collagen molecules, nicotinamide, and exendin-4 are beneficial for MSCs differentiation into islet-like cells. These nano collagen molecules may lead to alternations or up-regulation of gene expression and influence the differentiated outcomes induced by nicotinamide and exendin-4.

Keywords: nano collagen molecules, nicotinamide, MSCs, diabetes

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16 Effect of Madecassoside on the Antioxidant Status of Streptozotocin-Nicotinamide Induced Diabetes in Sprague-Dawley Rats

Authors: C. Mayuren, C. K. Paul Wang, K. Purushotham, C. Dinesh Kumar

Abstract:

Diabetes Mellitus (DM) is one of the most common non-communicable diseases globally. Although significant advances have led to better understanding of the condition and the development of effective therapies and preventive strategies, the pathway to cure remains elusive and DM prevails as a serious medical challenge in the 21st century. Oxidative stress has been suggested to contribute to the progression and pathophysiological conditions of diabetes. Madecassoside (MA) a major pentacyclic triterpenoid, has been demonstrated to possess various biological activities. However, no attempt has been made to study the antioxidant activity in diabetic rats. Therefore, the present study is aimed to evaluate the antioxidant effect of MA on streptozotocin-nicotinamide induced type-2 diabetes in Sprague-Dawley rats. The study protocol was approved by the institutional ethical committee prior to the conduct of research. Adult male Sprague-Dawley rats weighing 250-300 g were used in the study. The animals were rendered diabetic with a single intraperitoneal dose of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). The diabetic animals after a stabilisation period of 14 days received various treatments (Madecassoside 50 mg/kg; Glimepiride 2.5 mg/kg) suspended in 0.5% carboxymethyl cellulose orally, for a period of 28 days. The animals fasted overnight after the last treatment were sacrificed and the pancreas, liver and kidneys were isolated. The weighted quantity of the samples of various treatments were homogenised in ice-cold condition and were subjected to lipid peroxidation, catalase and superoxide dismutase assay. The data’s obtained were subjected to statistical analysis. Diabetic rats showed significant increase in lipid peroxidation and decrease in enzymatic antioxidant levels. All the treated groups had significantly higher SOD, CAT and reduced LPO activity in the pancreas, liver and kidney. Results suggest madecassoside to have potential antioxidant effect against the diabetic model. However further investigations are necessary to study the mechanism at the cellular level.

Keywords: antioxidant, diabetes, madecassoside, nicotinamide, streptozotocin

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15 Cocrystal of Mesalamine for Enhancement of Its Biopharmaceutical Properties, Utilizing Supramolecular Chemistry Approach

Authors: Akshita Jindal, Renu Chadha, Maninder Karan

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Supramolecular chemistry has gained recent eminence in a flurry of research documents demonstrating the formation of new crystalline forms with potentially advantageous characteristics. Mesalamine (5-amino salicylic acid) belongs to anti-inflammatory class of drugs, is used to treat ulcerative colitis and Crohn’s disease. Unfortunately, mesalamine suffer from poor solubility and therefore very low bioavailability. This work is focused on preparation and characterization of cocrystal of mesalamine with nicotinamide (MNIC) a coformer of GRAS status. Cocrystallisation was achieved by solvent drop grinding in stoichiometric ratio of 1:1 using acetonitrile as solvent and was characterized by various techniques including DSC (Differential Scanning Calorimetry), PXRD (X-ray Powder Diffraction), and FTIR (Fourier Transform Infrared Spectrometer). The co-crystal depicted single endothermic transitions (254°C) which were different from the melting peaks of both drug (288°C) and coformer (128°C) indicating the formation of a new solid phase. Different XRPD patterns and FTIR spectrums for the co-crystals from those of individual components confirms the formation of new phase. Enhancement in apparent solubility study and intrinsic dissolution study showed effectiveness of this cocrystal. Further improvement in pharmacokinetic profile has also been observed with 2 folds increase in bioavailability. To conclude, our results show that application of nicotinamide as a coformer is a viable approach towards the preparation of cocrystals of potential drug molecule having limited solubility.

Keywords: cocrystal, mesalamine, nicotinamide, solvent drop grinding

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14 Antidiabetic and Antioxidant Potential of Aqueous Extract of Jasminum humile Leaves in Nicotinamide/Streptozotocin induced Type-2 Diabetes Mellitus (T2DM) Rat

Authors: Parminder Nain, Jaspreet kaur, Vipin Saini, Sunil Sharma

Abstract:

Jasminum humile commonly known as yellow Jasmine or Pili chameli, is a medicinal plant used in Ayurveda for treating various diseases, one of which is diabetes mellitus. The current study aimed to establish the antidiabetic and antioxidant properties of aqueous extract of Jasminum humile leaves (AEJHL) in nicotinamide/streptozotocin induced type 2 diabetic rats. Phytochemical screening, HPLC analysis, and acute toxicity study of AEJHL were carried out. Male albino wistar rats (n=42) were divided into seven equal groups. Rats with moderate diabetes having hyperglycemia (blood glucose 250-400 mg/dl) were taken for the experiment. Various concentrations of aqueous extract of Jasminum humile leaves (50, 100, 200 and 300 mg/kg, p.o.), and glibenclamide (1mg/kg, p.o.) were orally administered to diabetic rats for 45 days. The effect of AEJHL on blood glucose, plasma insulin and biochemical parameters such as hemoglobin, total protein, serum creatinine, serum urea, alkaline phosphate, Glutamic-oxalacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT), as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. The antioxidant effect of AEJHL was determined by analyzing hepatic and renal antioxidant markers, like superoxide dismutase (SOD), catalase (CAT), reduced Glutathione (GSH), Glutathione peroxidase (GPx), and lipid peroxidation (LPO) in diabetic rats. After 45-days oral administration of aqueous extract of Jasminum humile leaves significantly (p<0.05) reduced blood sugar and increase plasma insulin level and also reverse all above biochemical parameters and antioxidant enzyme level at dose dependent manner. These findings provide in vivo evidence that the aqueous extract of Jasminum humile leaves possess significant antidiabetic and antioxidant potential in nicotinamide/streptozotocin-induced type-2 diabetes mellitus in rats.

Keywords: antidiabetic, antioxidant, jasminum humile, nicotinamide/streptozotocin, type-2 diabetic

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13 Effect of Goat Milk Kefir and Soy Milk Kefir on IL-6 in Diabetes Mellitus Wistar Mice Models Induced by Streptozotocin and Nicotinamide

Authors: Agatha Swasti Ayuning Tyas

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Hyperglycemia in Diabetes Mellitus (DM) is an important factor in cellular and vascular damage, which is caused by activation of C Protein Kinase, polyol and hexosamine track, and production of Advanced Glycation End-Products (AGE). Those mentioned before causes the accumulation of Reactive Oxygen Species (ROS). Oxidative stress increases the expression of proinflammatory factors IL-6 as one of many signs of endothelial disfunction. Genistein in soy milk has a high immunomodulator potential. Goat milk contains amino acids which have antioxidative potential. Fermented kefir has an anti-inflammatory activity which believed will also contribute in potentiating goat milk and soy milk. This study is a quasi-experimental posttest-only research to 30 Wistar mice. This study compared the levels of IL-6 between healthy Wistar mice group (G1) and 4 DM Wistar mice with intervention and grouped as follows: mice without treatment (G2), mice treated with 100% goat milk kefir (G3), mice treated with combination of 50% goat milk kefir and 50% soy milk kefir (G4), and mice treated with 100% soy milk kefir (G5). DM animal models were induced with Streptozotocin & Nicotinamide to achieve hyperglycemic condition. Goat milk kefir and soy milk kefir are given at a dose of 2 mL/kg body weight/day for four weeks to intervention groups. Blood glucose was analyzed by the GOD-POD principle. IL-6 was analyzed by enzyme-linked sandwich ELISA. The level of IL-6 in DM untreated control group (G2) showed a significant difference from the group treated with the combination of 50% goat milk kefir and 50% soy milk kefir (G3) (p=0,006) and the group treated with 100% soy milk kefir (G5) (p=0,009). Whereas the difference of IL-6 in group treated with 100% goat milk kefir (G3) was not significant (p=0,131). There is also synergism between glucose level and IL-6 in intervention groups treated with combination of 50% goat milk kefir and 50% soy milk kefir (G3) and the group treated with 100% soy milk kefir (G5). Combination of 50 % goat milk kefir and 50% soy milk kefir and administration of 100% soy milk kefir alone can control the level of IL-6 remained low in DM Wistar mice induced with streptozocin and nicotinamide.

Keywords: diabetes mellitus, goat milk kefir, soy milk kefir, interleukin 6

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12 Cucurbita pepo L. Attenuates Diabetic Neuropathy by Targeting Oxidative Stress in STZ-Nicotinamide Induced Diabetic Rats

Authors: Navpreet Kaur, Randhir Singh

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Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. The present study targeted oxidative stress mediated nerve damage in diabetic rats using a hydro-alcohol extract of Cucurbita pepo L. (Family: Cucurbitaceae) and its potential in treatment of diabetic neuropathy. Diabetes neuropathy was induced in Wistar rats by injection of streptozotocin (65 mg/kg, i.p.) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Hydro-alcohol extract of C. pepo seeds was assessed by oral administration at 100, 200 and 400 mg/kg in STZ-nicotinamide induced diabetic rats. Thermal hyperalgesia (Eddy's hot plate and tail immersion), mechanical hyperalgesia (Randall-Selitto) and tactile allodynia (Von Frey hair tests) were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy. Tissue (sciatic nerve) antioxidant enzymes (SOD, CAT, GSH and LPO) levels were measured along with the formation of AGEs in serum to assess the effect of hydro-alcohol extract of C. pepo in ameliorating oxidative stress. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test and decreased paw withdrawal threshold in both Randall-Selitto and von-Frey hair test. A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress in sciatic nerve of diabetic rats. Treatment with the C. pepo hydro-alcohol extract significantly attenuated all the behavioral and biochemical alterations in a dose-dependent manner. C. pepo attenuated the diabetic condition and also reversed neuropathic pain through modulation of oxidative stress and thus it may find application as a possible therapeutic agent against diabetic neuropathy.

Keywords: advanced glycation end products, antioxidant enzymes, cucurbita pepo, hyperglycemia

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11 Mitochondrial Energy Utilization is Unchanged with Age in the Trophocytes and Oenocytes of Queen Honeybees (Apis mellifera)

Authors: Chia-Ying Yen, Chin-Yuan Hsu

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The lifespans of queen honeybees (Apis mellifera) are much longer than those of worker bees. The expression, concentration, and activity of mitochondrial energy-utilized molecules decreased with age in the trophocytes and oenocytes of worker bees, but they are unknown in queen bees. In this study, the expression, concentration, and activity of mitochondrial energy-utilized molecules were evaluated in the trophocytes and oenocytes of young and old queen bees by biochemical techniques. The results showed that mitochondrial density and mitochondrial membrane potential; nicotinamide adenine dinucleotide (NAD+), nicotinamide adenine dinucleotide reduced form (NADH), and adenosine triphosphate (ATP) levels; the NAD+/NADH ratio; and relative expression of NADH dehydrogenase 1 and ATP synthase normalized against mitochondrial density were not significantly different between young and old queen bees. These findings reveal that mitochondrial energy utilization maintains a young status in the trophocytes and oenocytes of old queen bees and that trophocytes and oenocytes have aging-delaying mechanisms and can be used to study cellular longevity.

Keywords: aging, longevity, mitochondrial energy, queen bees

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10 Cocrystals of Etodolac: A Crystal Engineering Approach with an Endeavor to Enhance Its Biopharmaceutical Assets

Authors: Sakshi Tomar, Renu Chadha

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Cocrystallization comprises a selective route to the intensive design of pharmaceutical products with desired physiochemical and pharmacokinetic properties. The present study is focused on the preparation, characterization, and evaluation of etodolac (ET) co-crystals with coformers nicotinamide (ETNI) and Glutaric acid (ETGA), using cocrystallization approach. Preliminarily examination of the prepared co-crystal was done by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermographs of ETNI and ETGA cocrystals showed single sharp melting endotherms at 144°C and 135°C, respectively, which were different from the melting of drugs and coformers. FT-IR study points towards carbonyl-acid interaction sandwiched between the involving molecules. The emergence of new peaks in the PXRD pattern confirms the formation of new crystalline solid forms. Both the cocrystals exhibited better apparent solubility, and 3.8-5.0 folds increase in IDR were established, as compared to pure etodolac. Evaluations of these solid forms were done using anti-osteoarthritic activities. All the results indicate that etodolac cocrystals possess better anti-osteoarthritic efficacy than free drug. Thus loom of cocrystallization has been found to be a viable approach to resolve the solubility and bioavailability issues that circumvent the use of potential antiosteoarthritic molecules.

Keywords: bioavailability, etodolac, nicotinamide, osteoarthritis

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9 Renoprotective Effect of Alcoholic Extract of Bacopa monnieri via Inhibition of Advanced Glycation End Products and Oxidative Stress in Stz-Nicotinamide Induced Diabetic Nephropathy

Authors: Lalit Kishore, Randhir Singh

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Diabetic nephropathy (DN) is the major cause of morbidity among diabetic patients. In this study, the effect of Bacopa monnieri Linn. (Brahmi, BM), was studied in a Streptozotocin (STZ)-induced experimental rat model of DN. Diabetic nephropathy was induced in Male Wistar rats (body weight- 300± 10 gms) by single intra-peritoneal injection of STZ (45mg/kg, i.p.) after 15 min of Nicotinamide (230 mg/kg) administration. Different doses of alcoholic extract i.e. 100, 200 and 400 mg/kg was given for 45 days by oral gavage after induction of DN. Blood glucose level, serum insulin, glycosylated haemoglobin, renal parameters (serum urea, uric acid, creatinine and BUN) and lipid profile (total cholesterol, triglycerides, HDL, LDL and VLDL levels) were measured. Concentration of thiobarbituric acid reactive species (TBARS) and levels of antioxidant enzymes of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the kidney, liver and pancreas. At the end of treatment period the alcoholic extract of BM reduced the elevated level of blood glucose, serum insulin, renal parameters, lipid levels, TBARS, AGE’s in kidney and significantly increased body weight, HDL and antioxidant enzymes in dose dependent manner as compared to diabetic control animals. These results suggested the BM possesses significant renoprotective activity.

Keywords: AGE's, lipid profile, oxidative stress, renal parameters

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8 The Effect of Radish (Raphanus Sativus L.) Leaves Ethanol Extract on Blood Glucose Levels in Streptozotocin-Nicotinamide-Induced Type-2 Diabetic Rats

Authors: Satria B. Mahathma, Asri Hendrawati

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Background: Diabetes mellitus (DM) is a metabolic disorder syndrome characterized by chronic hyperglycemia. The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. In general, almost 90% of the prevalence of DM is type 2 DM which marked by insulin resistance and decreased receptor sensitivity. Aside from conventional antidiabetic therapy, the utilization of medicinal plants as alternative medicine has beneficial effects in diabetic patients. Flavonoid contents in radish leaves such as quercetin, pelargonidin, and kaempferol are thought to have antidiabetic activity on decreasing blood glucose levels by tricyclic nucleotide modulation of pancreatic beta cells and ameliorating insulin resistance. This study aimed to determine the effect of variant concentration of radish leaves ethanol extract on blood glucose levels in diabetic rats. Method: This study used pretest-posttest control group design by using 16 male Wistar rats which were induced type-2 diabetic by streptozotocin 60 mg/kg BW-nicotinamide 120 mg/kg BW intraperitoneally. Rats who had developed type-2 DM later divided randomly into 4 groups; negative control received placebo, positive control received glibenclamide 5 mg/kg BW/day, rats intervention I and intervention II received 100% and 50% of radish leaves ethanol extract, respectively. Treatments were administered orally for four weeks. The blood glucose levels were measured using the Enzymatic Colorimetric Test “GOD-PAP”. Data were analyzed by the dependent t-test for pretest-posttest intervention difference and one-way ANOVA followed by post hoc test to determine the significant difference of each treatment to obtain the significant data. Result: The result revealed that intervention group had lower blood glucose levels mean than control group which the lowest was intervention II group (negative control: 540,9 ± 191,7 mg/dl, positive control: 494, 97 ± 64,91 mg/dl, intervention I: 301,92 ± 165,70 mg/dl, and intervention II group: 276,1 ± 139,02 mg/dl. Intervention II group had the highest antidiabetic activity, followed by the intervention I group with the amount of decrease in blood glucose levels were -151,85 ± 77,43 mg/dl and -11,08 ± 186,62 mg/dl, however negative and positive control group didn’t have antidiabetic activity. The dependent t-test result showed there is a significant difference in decreasing blood glucose levels in the intervention II pretest-posttest intervention (p=0,03) while the other group didn’t. Data analyzed by one-way ANOVA also revealed the intervention II group significantly declined blood glucose levels compared to the negative and positive control group (p = 0,033 and p=0,032, respectively). Conclusion: There is a significant effect of radish leaves ethanol extract on blood glucose levels in streptozotocin-nicotinamide-induced diabetic rats with the optimal therapeutic effect at a concentration of 50%.

Keywords: blood glucose levels, medicinal plant, radish leaves, type-2 diabetes mellitus

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7 Mixed Hydrotropic Zaleplon Oral Tablets: Formulation and Neuropharmacological Effect on Plasma GABA Level

Authors: Ghada A. Abdelbary, Maha M. Amin, Mostafa Abdelmoteleb

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Zaleplon (ZP) is a non-benzodiazepine poorly soluble hypnotic drug indicated for the short term treatment of insomnia having a bioavailability of about 30%. The aim of the present study is to enhance the solubility and consequently the bioavailability of ZP using hydrotropic agents (HA). Phase solubility diagrams of ZP in presence of different molar concentrations of HA (Sodium benzoate, Urea, Ascorbic acid, Resorcinol, Nicotinamide, and Piperazine) were constructed. ZP/Sodium benzoate and Resorcinol microparticles were prepared adopting melt, solvent evaporation and melt-evaporation techniques followed by XRD. Directly compressed mixed hydrotropic ZP tablets of Sodium benzoate and Resorcinol in different weight ratios were prepared and evaluated compared to the commercially available tablets (Sleep aid® 5 mg). The effect of shelf and accelerated stability storage (40°C ± 2°C/75%RH ± 5%RH) on the optimum tablet formula (F5) for six months were studied. The enhancement of ZP solubility follows the order of: Resorcinol > Sodium benzoate > Ascorbic acid > Piperazine > Urea > Nicotinamide with about 350 and 2000 fold increase using 1M of Sodium benzoate and Resorcinol respectively. ZP/HA microparticles exhibit the order of: Solvent evaporation > melt-solvent evaporation > melt > physical mixture which was further confirmed by the complete conversion of ZP into amorphous form. Mixed hydrotropic tablet formula (F5) composed of ZP/(Resorcinol: Sodium benzoate 4:1w/w) microparticles prepared by solvent evaporation exhibits in-vitro dissolution of 31.7±0.11% after five minutes (Q5min) compared to 10.0±0.10% for Sleep aid® (5 mg) respectively. F5 showed significantly higher GABA concentration of 122.5±5.5mg/mL in plasma compared to 118±1.00 and 27.8±1.5 mg/mL in case of Sleep aid® (5 mg) and control taking only saline respectively suggesting a higher neuropharmacological effect of ZP following hydrotropic solubilization.

Keywords: zaleplon, hydrotropic solubilization, plasma GABA level, mixed hydrotropy

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6 In vivo Antidiabetic and Antioxidant Potential of Pseudovaria macrophylla Extract

Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

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This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMS-QTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg∙bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid

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5 Pd(II) Complex with 4-Bromo-2,6-Bis-Hydroxymethyl-Phenol and Nikotinamid: Synthesis and Spectral Analysis

Authors: Özlen Altun, Zeliha Yoruç

Abstract:

In the present study, the reactions involving 4-Bromo-2,6-bis-hydroxymethyl-phenol (BBHMP) and nikotinamide (NA) in the presence Pd (II) ion were investigated. Optimum conditions for the reactions were established as pH 7 and λ = 450 nm. According to absorbance measurements, the mole ratio of BBHMP : NA : Pd2+ was found as 1 : 2 : 2. As a result of physico-chemical, spectrophotometric and thermal analysis results, the reactions of BBHMP and NA with Pd (II) is complexation reactions and one molecule BBHMP and two molecules of NA react with two molecules of metal (II) ion.

Keywords: 4-Bromo-2, 6-bis-hydroxymethyl-phenol, nicotinamide, Pd(II), spectral analysis, synthesis

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4 A High-Throughput Enzyme Screening Method Using Broadband Coherent Anti-stokes Raman Spectroscopy

Authors: Ruolan Zhang, Ryo Imai, Naoko Senda, Tomoyuki Sakai

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Enzymes have attracted increasing attentions in industrial manufacturing for their applicability in catalyzing complex chemical reactions under mild conditions. Directed evolution has become a powerful approach to optimize enzymes and exploit their full potentials under the circumstance of insufficient structure-function knowledge. With the incorporation of cell-free synthetic biotechnology, rapid enzyme synthesis can be realized because no cloning procedure such as transfection is needed. Its open environment also enables direct enzyme measurement. These properties of cell-free biotechnology lead to excellent throughput of enzymes generation. However, the capabilities of current screening methods have limitations. Fluorescence-based assay needs applicable fluorescent label, and the reliability of acquired enzymatic activity is influenced by fluorescent label’s binding affinity and photostability. To acquire the natural activity of an enzyme, another method is to combine pre-screening step and high-performance liquid chromatography (HPLC) measurement. But its throughput is limited by necessary time investment. Hundreds of variants are selected from libraries, and their enzymatic activities are then identified one by one by HPLC. The turn-around-time is 30 minutes for one sample by HPLC, which limits the acquirable enzyme improvement within reasonable time. To achieve the real high-throughput enzyme screening, i.e., obtain reliable enzyme improvement within reasonable time, a widely applicable high-throughput measurement of enzymatic reactions is highly demanded. Here, a high-throughput screening method using broadband coherent anti-Stokes Raman spectroscopy (CARS) was proposed. CARS is one of coherent Raman spectroscopy, which can identify label-free chemical components specifically from their inherent molecular vibration. These characteristic vibrational signals are generated from different vibrational modes of chemical bonds. With the broadband CARS, chemicals in one sample can be identified from their signals in one broadband CARS spectrum. Moreover, it can magnify the signal levels to several orders of magnitude greater than spontaneous Raman systems, and therefore has the potential to evaluate chemical's concentration rapidly. As a demonstration of screening with CARS, alcohol dehydrogenase, which converts ethanol and nicotinamide adenine dinucleotide oxidized form (NAD+) to acetaldehyde and nicotinamide adenine dinucleotide reduced form (NADH), was used. The signal of NADH at 1660 cm⁻¹, which is generated from nicotinamide in NADH, was utilized to measure the concentration of it. The evaluation time for CARS signal of NADH was determined to be as short as 0.33 seconds while having a system sensitivity of 2.5 mM. The time course of alcohol dehydrogenase reaction was successfully measured from increasing signal intensity of NADH. This measurement result of CARS was consistent with the result of a conventional method, UV-Vis. CARS is expected to have application in high-throughput enzyme screening and realize more reliable enzyme improvement within reasonable time.

Keywords: Coherent Anti-Stokes Raman Spectroscopy, CARS, directed evolution, enzyme screening, Raman spectroscopy

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3 Sirt1 Promotes C2C12 Myoblast Cell Proliferation by Myostatin Signaling Pathway

Authors: Cuili Yang, Chengcao Sun, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

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Backgrounds: Previous studies showed that Sirt1 plays an important role in C2C12 myoblast cell proliferation, but the mechanism(s) involved in this process remains unclear. This work was undertaken to determine if Myostatin participates in the regulation of C2C12 proliferation by Sirt1. Methods: We administrated the Sirt1 activator resveratrol, inhibitor Nicotinamide (NAM) and Myostatin inhibitor SB431542 on C2C12 myoblast cells. Cell viability was evaluated by CCK8 assay. The expression of Sirt1 and MyoD were detected by qRT-PCR. Utilizing western blot to determinate the expression of myostatin, P107 and p-P107. Results: Our results showed that resveratrol promoted the proliferation of C2C12 myoblast cells, while NAM suppressed the proliferation of C2C12 myoblast cells; SB431542 promoted the proliferation of C2C12 myoblast cells and attenuated the inhibition effect of NAM on C2C12 myoblast cells proliferation; Resveratrol can significantly increase the expression of Sirt1 and MyoD, decrease the expression of Myostatin, while NAM can significantly down-regulate the expression of Sirt1, MyoD and the phosphorylation of P107(p-P107), but up-regulate the expression of Myostatin and the protein P107; SB431542 can significantly mitigate the effect of NAM on the expression of MyoD, P107, and p-P107. Conclusions: Taken together, these results indicate that Sirt1 promotes the proliferation of C2C12 myoblast cells via Myostatin signaling pathway.

Keywords: Sirt1, C2C12 cells, proliferation, myostatin signaling pathway

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2 Application of Mesenchymal Stem Cells in Diabetic Therapy

Authors: K. J. Keerthi, Vasundhara Kamineni, A. Ravi Shanker, T. Rammurthy, A. Vijaya Lakshmi, Q. Hasan

Abstract:

Pancreatic β-cells are the predominant insulin-producing cell types within the Islets of Langerhans and insulin is the primary hormone which regulates carbohydrate and fat metabolism. Apoptosis of β-cells or insufficient insulin production leads to Diabetes Mellitus (DM). Current therapy for diabetes includes either medical management or insulin replacement and regular monitoring. Replacement of β- cells is an attractive treatment option for both Type-1 and Type-2 DM in view of the recent paper which indicates that β-cells apoptosis is the common underlying cause for both the Types of DM. With the development of Edmonton protocol, pancreatic β-cells allo-transplantation became possible, but this is still not considered as standard of care due to subsequent requirement of lifelong immunosuppression and the scarcity of suitable healthy organs to retrieve pancreatic β-cell. Fetal pancreatic cells from abortuses were developed as a possible therapeutic option for Diabetes, however, this posed several ethical issues. Hence, in the present study Mesenchymal stem cells (MSCs) were differentiated into insulin producing cells which were isolated from Human Umbilical cord (HUC) tissue. MSCs have already made their mark in the growing field of regenerative medicine, and their therapeutic worth has already been validated for a number of conditions. HUC samples were collected with prior informed consent as approved by the Institutional ethical committee. HUC (n=26) were processed using a combination of both mechanical and enzymatic (collagenase-II, 100 U/ml, Gibco ) methods to obtain MSCs which were cultured in-vitro in L-DMEM (Low glucose Dulbecco's Modified Eagle's Medium, Sigma, 4.5 mM glucose/L), 10% FBS in 5% CO2 incubator at 37°C. After reaching 80-90% confluency, MSCs were characterized with Flowcytometry and Immunocytochemistry for specific cell surface antigens. Cells expressed CD90+, CD73+, CD105+, CD34-, CD45-, HLA-DR-/Low and Vimentin+. These cells were differentiated to β-cells by using H-DMEM (High glucose Dulbecco's Modified Eagle's Medium,25 mM glucose/L, Gibco), β-Mercaptoethanol (0.1mM, Hi-Media), basic Fibroblast growth factor (10 µg /L,Gibco), and Nicotinamide (10 mmol/L, Hi-Media). Pancreatic β-cells were confirmed by positive Dithizone staining and were found to be functionally active as they released 8 IU/ml insulin on glucose stimulation. Isolating MSCs from usually discarded, abundantly available HUC tissue, expanding and differentiating to β-cells may be the most feasible cell therapy option for the millions of people suffering from DM globally.

Keywords: diabetes mellitus, human umbilical cord, mesenchymal stem cells, differentiation

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1 Innovative Technologies Functional Methods of Dental Research

Authors: Sergey N. Ermoliev, Margarita A. Belousova, Aida D. Goncharenko

Abstract:

Application of the diagnostic complex of highly informative functional methods (electromyography, reodentography, laser Doppler flowmetry, reoperiodontography, vital computer capillaroscopy, optical tissue oximetry, laser fluorescence diagnosis) allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment. Introduction. It is necessary to create a complex of innovative highly informative and safe functional diagnostic methods for improvement of the quality of patient treatment by the early detection of stomatologic diseases. The purpose of the present study was to investigate the etiology and pathogenesis of functional disorders identified in the pathology of hard tissue, dental pulp, periodontal, oral mucosa and chewing function, and the creation of new approaches to the diagnosis of dental diseases. Material and methods. 172 patients were examined. Density of hard tissues of the teeth and jaw bone was studied by intraoral ultrasonic densitometry (USD). Electromyographic activity of masticatory muscles was assessed by electromyography (EMG). Functional state of dental pulp vessels assessed by reodentography (RDG) and laser Doppler flowmetry (LDF). Reoperiodontography method (RPG) studied regional blood flow in the periodontal tissues. Microcirculatory vascular periodontal studied by vital computer capillaroscopy (VCC) and laser Doppler flowmetry (LDF). The metabolic level of the mucous membrane was determined by optical tissue oximetry (OTO) and laser fluorescence diagnosis (LFD). Results and discussion. The results obtained revealed changes in mineral density of hard tissues of the teeth and jaw bone, the bioelectric activity of masticatory muscles, regional blood flow and microcirculation in the dental pulp and periodontal tissues. LDF and OTO methods estimated fluctuations of saturation level and oxygen transport in microvasculature of periodontal tissues. With LFD identified changes in the concentration of enzymes (nicotinamide, flavins, lipofuscin, porphyrins) involved in metabolic processes Conclusion. Our preliminary results confirmed feasibility and safety the of intraoral ultrasound densitometry technique in the density of bone tissue of periodontium. Conclusion. Application of the diagnostic complex of above mentioned highly informative functional methods allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment.

Keywords: electromyography (EMG), reodentography (RDG), laser Doppler flowmetry (LDF), reoperiodontography method (RPG), vital computer capillaroscopy (VCC), optical tissue oximetry (OTO), laser fluorescence diagnosis (LFD)

Procedia PDF Downloads 204