Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizi... more Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizine fluoroquinolone, levonadifloxacin, was evaluated in lipopolysaccharide-stimulated human whole-blood (HWB) and mouse acute lung injury (ALI) models. Levonadifloxacin significantly mitigated the inflammatory responses in an HWB assay through inhibition of proinflammatory cytokines and in the ALI model by lowering lung total white blood cell count, myeloperoxidase, and cytokine levels. The immunomodulatory effect of levonadifloxacin, along with promising antibacterial activity, is expected to provide clinical benefits in the treatment of infections.
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. Though different types ... more Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. Though different types of oral hypoglycemic agents are available, there is a growing interest in herbal remedies due to effectiveness, minimal side effects in clinical experience and relatively low cost. We investigated effect of oral administration of 100 and 200 mg/kg of ethanolic extract of Mukia maderaspatana in diabetic and normal rats for hypoglycemic activity and antihypergylcemic activity. Diabetes was induced in male wistar albino rats of body weight 150–200 g by intraperitoneal administration of ice-cold aqueous alloxan monohydrate at dose of 150 mg/kg. Blood samples were collected for the measurement of blood glucose from the tail vein at 0, 1, 3, and 5 hr post treatment with plant extract. Glibenclamide was used as standard drug. The fasting blood glucose levels of diabetic untreated rats were significantly higher than those of normal. The ethanolic extracts of Mukia maderaspatana at 100 and 200 mg/kg showed 20% and 24.4% decrease in blood glucose level respectively in diabetic rats after 5 h of treatment. Treatment with glibenclamide at 0.2 g/kg dose level show 31.8% decrease in blood glucose level in diabetic rats. The present study revealed that the oral administration of ethanolic extracts at 100 and 200 mg/kg doses exhibited a significant antihyperglycemic activity in alloxan induced diabetes and also no hypoglycemic effect was observed in normal rats.
International Journal of Diabetes in Developing Countries, 2013
ABSTRACT ‘Diabetic encephalopathy’ refers to diabetes associated cognitive decline (DACD), which ... more ABSTRACT ‘Diabetic encephalopathy’ refers to diabetes associated cognitive decline (DACD), which involves oxidative-nitrosative stress, inflammation and cholinergic dysfunction. Current study was designed to investigate the effect of Adhatoda vasica, a known anti-inflammatory, antioxidant, anti-cholinesterase and anti-hyperglycemic plant, on diabetic encephalopathy. Streptozotocin (STZ)-induced diabetic Wistar rats were treated with Adhatoda vasica leaves ethanolic extract (AVEE) for 6 weeks at 100, 200 and 400 mg/kg/day dose. During fifth week of treatment, learning and memory was investigated in single Y-maze and passive avoidance test. At the end of the study biochemical parameters like acetylcholinesterase (AchE) activity, nitrite levels, tumor necrosis factor-alpha (TNF-α) and oxidative stress was measured from cerebral cortex and hippocampus regions of brain. AchE activity was found increased by 70 % in the cerebral cortex of diabetic rat brain. Lipid peroxidation (LPO) levels were increased by 100 % and 94 % in cerebral cortex and hippocampus of diabetic rats, respectively. Non-protein thiol levels, enzymatic activities of superoxide dismutase and catalase were found decreased in cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in both regions of diabetic brain were increased by 170 % and 137 % respectively. TNF-α, a pro-inflammatory cytokine, was found significantly increased in diabetic rats. Conversely, animal groups treated with AVEE significantly attenuated these behavioral and biochemical abnormalities. The results suggest a protective role of Adhatoda vasica Nees against diabetic encephalopathy, which may be sum of its anti-oxidant, anti-cholinesterase, anti-inflammatory and glucose lowering action.
Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as... more Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin.
Three series of novel glitazones were designed and prepared by using appropriate synthetic scheme... more Three series of novel glitazones were designed and prepared by using appropriate synthetic schemes to incorporate glycine, aromatic and alicyclic amines via two carbon linker. Compounds were synthesized both under conventional and microwave methods. Nineteen out of twenty four synthesized compounds were evaluated for their in vitro glucose uptake activity using isolated rat hemi-diaphragm. Compounds, 6, 9a, 13a, 13b, 13c, 13f and 13h exhibited significant glucose uptake activity. Illustration about their synthesis and in vitro glucose uptake activity is described along with the structure-activity relationships.
Ivabradine, a selective inhibitor of the pacemaker current in the sinoatrial node, has shown pure... more Ivabradine, a selective inhibitor of the pacemaker current in the sinoatrial node, has shown pure heart rate (HR)-reducing effects with anti-ischemic efficacy as well as improvement in heart failure outcomes. The purpose of this study was to explore pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and tolerability in healthy male Korean volunteers, as well as to compare them with PK/PD profiles of white subjects. This was a randomized, double-blind, placebo-controlled Phase I study conducted in healthy male subjects. For each of the 3 dosing groups, 9 subjects were randomized to receive ivabradine and 3 to receive placebo. Subjects received a single oral dose of ivabradine 2.5, 5, or 10 mg and after a 3-day washout period, repeat doses of 2.5, 5, or 10 mg BID for 4.5 days. Blood and urine samples were collected over 72 hours during each period, and levels of ivabradine and its metabolite S18982 were determined by using validated LC-MS/MS, followed by noncompartmental PK analysis. For PD properties and tolerability, 24-hour Holter recordings were obtained: at baseline, after a single dose, after repeated doses, and after the last dose. Serial resting 12-lead ECG assessments were also performed throughout the study. Forty-eight subjects were enrolled, and 45 completed the study. After single doses of 2.5, 5, and 10 mg, respective mean Cmax levels of ivabradine were 9, 15, and 39 ng/mL, and mean AUC0-last values were 30, 52, and 121 ng h/mL. At steady state, mean Cmax,ss levels were 11, 19, and 42 ng/mL, reached at a median Tmax of 0.67 hour for all 3 doses. The mean AUC0-τ levels were 43, 58, and 139 ng h/mL, respectively. The PK findings were linear with dose and time. Decreases in mean HR on both the Holter recordings and ECGs were observed in all of the ivabradine groups compared with placebo. After the repeated doses, mean decreases in HR were greater than those for the single doses for the same period. Statistically significant differences were observed between the 5- and 10-mg ivabradine groups and placebo. A total of 3 adverse events were reported in 2 subjects receiving ivabradine; both fully recovered without sequelae. Single and repeated administration of ivabradine were generally well tolerated in these healthy male Korean volunteers. Ivabradine induced significant reductions in HR, especially at doses of 5 and 10 mg. PK/PD characteristics were similar to those found in white subjects, suggesting that the dose concentration-response relationship of ivabradine is similar between Korean and white subjects.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizi... more Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizine fluoroquinolone, levonadifloxacin, was evaluated in lipopolysaccharide-stimulated human whole-blood (HWB) and mouse acute lung injury (ALI) models. Levonadifloxacin significantly mitigated the inflammatory responses in an HWB assay through inhibition of proinflammatory cytokines and in the ALI model by lowering lung total white blood cell count, myeloperoxidase, and cytokine levels. The immunomodulatory effect of levonadifloxacin, along with promising antibacterial activity, is expected to provide clinical benefits in the treatment of infections.
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. Though different types ... more Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. Though different types of oral hypoglycemic agents are available, there is a growing interest in herbal remedies due to effectiveness, minimal side effects in clinical experience and relatively low cost. We investigated effect of oral administration of 100 and 200 mg/kg of ethanolic extract of Mukia maderaspatana in diabetic and normal rats for hypoglycemic activity and antihypergylcemic activity. Diabetes was induced in male wistar albino rats of body weight 150–200 g by intraperitoneal administration of ice-cold aqueous alloxan monohydrate at dose of 150 mg/kg. Blood samples were collected for the measurement of blood glucose from the tail vein at 0, 1, 3, and 5 hr post treatment with plant extract. Glibenclamide was used as standard drug. The fasting blood glucose levels of diabetic untreated rats were significantly higher than those of normal. The ethanolic extracts of Mukia maderaspatana at 100 and 200 mg/kg showed 20% and 24.4% decrease in blood glucose level respectively in diabetic rats after 5 h of treatment. Treatment with glibenclamide at 0.2 g/kg dose level show 31.8% decrease in blood glucose level in diabetic rats. The present study revealed that the oral administration of ethanolic extracts at 100 and 200 mg/kg doses exhibited a significant antihyperglycemic activity in alloxan induced diabetes and also no hypoglycemic effect was observed in normal rats.
International Journal of Diabetes in Developing Countries, 2013
ABSTRACT ‘Diabetic encephalopathy’ refers to diabetes associated cognitive decline (DACD), which ... more ABSTRACT ‘Diabetic encephalopathy’ refers to diabetes associated cognitive decline (DACD), which involves oxidative-nitrosative stress, inflammation and cholinergic dysfunction. Current study was designed to investigate the effect of Adhatoda vasica, a known anti-inflammatory, antioxidant, anti-cholinesterase and anti-hyperglycemic plant, on diabetic encephalopathy. Streptozotocin (STZ)-induced diabetic Wistar rats were treated with Adhatoda vasica leaves ethanolic extract (AVEE) for 6 weeks at 100, 200 and 400 mg/kg/day dose. During fifth week of treatment, learning and memory was investigated in single Y-maze and passive avoidance test. At the end of the study biochemical parameters like acetylcholinesterase (AchE) activity, nitrite levels, tumor necrosis factor-alpha (TNF-α) and oxidative stress was measured from cerebral cortex and hippocampus regions of brain. AchE activity was found increased by 70 % in the cerebral cortex of diabetic rat brain. Lipid peroxidation (LPO) levels were increased by 100 % and 94 % in cerebral cortex and hippocampus of diabetic rats, respectively. Non-protein thiol levels, enzymatic activities of superoxide dismutase and catalase were found decreased in cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in both regions of diabetic brain were increased by 170 % and 137 % respectively. TNF-α, a pro-inflammatory cytokine, was found significantly increased in diabetic rats. Conversely, animal groups treated with AVEE significantly attenuated these behavioral and biochemical abnormalities. The results suggest a protective role of Adhatoda vasica Nees against diabetic encephalopathy, which may be sum of its anti-oxidant, anti-cholinesterase, anti-inflammatory and glucose lowering action.
Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as... more Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin.
Three series of novel glitazones were designed and prepared by using appropriate synthetic scheme... more Three series of novel glitazones were designed and prepared by using appropriate synthetic schemes to incorporate glycine, aromatic and alicyclic amines via two carbon linker. Compounds were synthesized both under conventional and microwave methods. Nineteen out of twenty four synthesized compounds were evaluated for their in vitro glucose uptake activity using isolated rat hemi-diaphragm. Compounds, 6, 9a, 13a, 13b, 13c, 13f and 13h exhibited significant glucose uptake activity. Illustration about their synthesis and in vitro glucose uptake activity is described along with the structure-activity relationships.
Ivabradine, a selective inhibitor of the pacemaker current in the sinoatrial node, has shown pure... more Ivabradine, a selective inhibitor of the pacemaker current in the sinoatrial node, has shown pure heart rate (HR)-reducing effects with anti-ischemic efficacy as well as improvement in heart failure outcomes. The purpose of this study was to explore pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and tolerability in healthy male Korean volunteers, as well as to compare them with PK/PD profiles of white subjects. This was a randomized, double-blind, placebo-controlled Phase I study conducted in healthy male subjects. For each of the 3 dosing groups, 9 subjects were randomized to receive ivabradine and 3 to receive placebo. Subjects received a single oral dose of ivabradine 2.5, 5, or 10 mg and after a 3-day washout period, repeat doses of 2.5, 5, or 10 mg BID for 4.5 days. Blood and urine samples were collected over 72 hours during each period, and levels of ivabradine and its metabolite S18982 were determined by using validated LC-MS/MS, followed by noncompartmental PK analysis. For PD properties and tolerability, 24-hour Holter recordings were obtained: at baseline, after a single dose, after repeated doses, and after the last dose. Serial resting 12-lead ECG assessments were also performed throughout the study. Forty-eight subjects were enrolled, and 45 completed the study. After single doses of 2.5, 5, and 10 mg, respective mean Cmax levels of ivabradine were 9, 15, and 39 ng/mL, and mean AUC0-last values were 30, 52, and 121 ng h/mL. At steady state, mean Cmax,ss levels were 11, 19, and 42 ng/mL, reached at a median Tmax of 0.67 hour for all 3 doses. The mean AUC0-τ levels were 43, 58, and 139 ng h/mL, respectively. The PK findings were linear with dose and time. Decreases in mean HR on both the Holter recordings and ECGs were observed in all of the ivabradine groups compared with placebo. After the repeated doses, mean decreases in HR were greater than those for the single doses for the same period. Statistically significant differences were observed between the 5- and 10-mg ivabradine groups and placebo. A total of 3 adverse events were reported in 2 subjects receiving ivabradine; both fully recovered without sequelae. Single and repeated administration of ivabradine were generally well tolerated in these healthy male Korean volunteers. Ivabradine induced significant reductions in HR, especially at doses of 5 and 10 mg. PK/PD characteristics were similar to those found in white subjects, suggesting that the dose concentration-response relationship of ivabradine is similar between Korean and white subjects.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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