Modification of ibuprofen to improve the medicinal effect; structural, biological, and toxicological study.

Ibuprofen is classified as a non-steroidal anti-inflammatory drug (NSAID) that is employed as an initial treatment option for its non-steroidal anti-inflammatory, pain-relieving, and antipyretic properties. However, Ibuprofen is linked to specific well-known gastrointestinal adverse effects like ulceration and gastrointestinal bleeding. It has been linked to harmful effects on the liver, kidney, and heart. The purpose of the study is to create novel and potential IBU analogue with reduced side effects with the enhancement of their medicinal effects, so as to advance the overall safety profile of the drug. The addition of some novel functional groups including CH3, F, CF3, OCF3, Cl, and OH at various locations in its core structure suggestively boost the chemical as well as biological action. The properties of these newly designed structures were analyzed through chemical, physical, and spectral calculations using Density Functional Theory (DFT) and time-dependent DFT through B3LYP/6-31 g (d,p) basis set for geometry optimization. Molecular docking and non-bonding interaction studies were conducted by means of the human prostaglandin synthase protein (PDB ID: 5F19) to predict binding affinity, interaction patterns, and the stability of the protein-drug complex. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and PASS (Prediction of Activity Spectra for Substances) predictions were employed to evaluate the pharmacokinetic and toxicological properties of these structures. Importantly, most of the analogues displayed reduced hepatotoxicity, nephrotoxicity, and carcinogenicity in comparison to the original drug. Moreover, molecular docking analyses indicated improved medicinal outcomes, which were further supported by pharmacokinetic calculations. Together, these findings suggest that the modified structures have reduced adverse effects along with improved therapeutic action compared to the parent drug.

Preparation and characterization of naproxen solid dispersion using different hydrophilic carriers and in-vivo evaluation of its analgesic activity in mice.

Background: Solid dispersion (SD) has been used conventionally as a successful technique for improving the dissolution profile and bioavailability of poorly water-soluble drugs. The aim of this study was to progress the dissolution rate and bioavailability of naproxen (BCS class II) by SD technique. Materials & methods: In this study, hydrophilic carriers are used for preparing solid dispersion of naproxen by evaporation method. The prepared optimized SDNs were evaluated by in-vitro drug dissolution test, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The in-vivo analgesic effects tests of the optimized SDNs (SDN-2 and SDN-5) were performed by tail immersion method and writhing method. Results: All the prepared SDNs exhibited a significant increase in the dissolution of naproxen compared to that of the pure drug. Among them, SDN-2 (the dispersion with sodium starch glycolate at 1:2 ratio of naproxen and sodium starch glycolate) and SDN-5 (using the combination of PEG-8000 and sodium starch glycolate with naproxen at 1:1:1 ratio) showed faster dissolution rate as compared to other solid dispersions (SDNs) and pure naproxen. SDN-2 showed 5.4 times better dissolution rate and SDN-5 depicted 6.5-fold increment of dissolution rate compared to pure naproxen drug. DSC, PXRD and SEM microscopy showed that the drugs crystallinity was decreased during the preparation process. FTIR study revealed that naproxen was stable in polymeric dispersions and there was no interaction among the drug and polymers. In writhing method, the percentage inhibition of the number of writhes showed significantly greater (p < 0.01), (p < 0.0001) analgesic activity for the higher dose treatment groups SDN-2(H), and SDN-5(H), respectively, when contrasted to the pure drug naproxen. For tail immersion test, there is increase in latency time at 90 min which is significantly greater (P < 0.01), (P < 0.05), (P < 0.01) for treatment groups SDN-2(H), SDN-5(L), and SDN-5(H), respectively that ultimately authenticates that the optimized SDNs (SDN-2, SDN-5) showed better analgesic activity in mice in comparison with the pure drug. Conclusion: It can be concluded that dissolution of the naproxen could be improved by the making solid dispersion using sodium starch glycolate and/or combination of sodium starch glycolate and PEG 8000 due to the complete transformation of drug into amorphous form with the entire loss of crystallinity, as evidenced by DSC, PXRD, and SEM and also consequences the enhanced analgesic activity in mice.

Cilnidipine and magnesium sulfate supplement ameliorates hyperglycemia, dyslipidemia and inhibits oxidative-stress in fructose-induced diabetic rats.

The study was designed to evaluate the safety and efficacy of cilnidipine (CLN) and Mg-supplementation in fructose-induced diabetic rats. Diabetes was induced into male Wister rats by feeding fructose (10% solution) in drinking water for 8 weeks. Diabetic rats were subjected for the oral administration of CLN1 (1 mg/kg/day) and CLN10 (10 mg/kg/day), and/or methyl cellulose (0.5%) as vehicle for 28 days. After 14 days of CLN treatment, MgSO4 (1%) was added to CLN1 and CLN10 groups for another 14 days. Age-matched healthy rats were used as normal control. After 28 days body weights were measured and organ weight to body ratio was calculated. Serum samples were analysed for fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), uric acid, lipid profiles, tri-iodothyronine (T3) and thyroid stimulating hormone (TSH), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), creatine phosphokinase myocardial-band (CK-MB), creatinine, albumin, electrolytes. Oral glucose tolerance tests (OGTT), liver histopathology and in-vivo antioxidant activities were also performed. The survival rate in diabetic rats was 100% after the oral administration of CLN, Mg-supplement and/or vehicle. A significant reduction in FBS levels and improvement in OGTT were observed in CLN10, CLN1+Mg and CLN10 + Mg groups after 28 days. Further, the treatment ameliorated serum lipid profile, uric acid, and albumin levels. The groups CLN10 and CLN10 + Mg improved HbA1c, liver glycogen, creatinine, T3, TSH levels and electrolytes in diabetic rats. Moreover, liver from CLN10 and CLN10 + Mg groups showed preservation of cellular architecture as evidenced by attenuation of inflammatory markers SGPT, SGOT and CK-MB; and the levels of superoxide dismutase (SOD), catalase (CAT), glutathione, malondialdehyde (MDA), markers of oxidative stress were significantly improved. CLN exerted prominent effects in the amelioration of hyperglycemia, dyslipidemia and reduced hepatic inflammation; and Mg-supplementation might have some beneficial effects on diabetic complications and oxidative stress in fructose-induced diabetic rats.

Dairy-Derived and Egg White Proteins in Enhancing Immune System Against COVID-19.

Coronavirus disease (COVID-19) is a global health challenge, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) triggers a plethora of respiratory disturbances and even multiple organs failure that can be fatal. Nutritional intervention is one of the key components toward to a proper management of COVID-19 patients, especially in those requiring medication, and should thus be considered the first-line treatment. Immuno-modulation and -stimulation are currently being explored in COVID-19 management and are gaining interest by food and pharmaceutical industries. Various dietary combinations, bioactive components, nutrients and fortified foods have been reported to modulate inflammation during disease progression. Dietary combinations of dairy-derived products and eggs are gaining an increasing attention given the huge immunomodulatory and anti-inflammatory properties attributed to some of their chemical constituents. Eggs are complex dietary components containing many essential nutrients and bioactive compounds as well as a high-quality proteins. Similarly, yogurts can replenish beneficial bacteria and contains macronutrients capable of stimulating immunity by enhancing cell immunity, reducing oxidative stress, neutralizing inflammation and regulating the intestinal barriers and gut microbiome. Thus, this review highlights the impact of nutritional intervention on COVID-19 management, focusing on the immunomodulatory and inflammatory effects of immune-enhancing nutrients.

Genetic Diversity of SARS-CoV2 and Environmental Settings: Possible Association with Neurological Disorders.

The new coronavirus (CoV), called novel coronavirus disease 2019 (COVID-19), belongs to the Coronaviridae family which was originated from the sea market in Wuhan city in China, at the end of the year 2019. COVID-19 and severe acute respiratory syndrome (SARS) are belonging to the same family (Coronaviridae). The current outbreak of COVID-19 creates public concern and threats all over the world and now it spreads out to more than 250 countries and territories. The researchers and scientists from all over the world are trying to find out the therapeutic strategies to abate the morbidity and mortality rate of the COVID-19 pandemic. The replication, spreading, and severity of SARS-CoV2 depend on environmental settings. Noteworthy, meteorological parameters are considered as crucial factors that affect respiratory infectious disorders, although the controversial effect of the meteorological parameter is exposed against COVID-19. Besides, COVID-19 accelerates the pathogenesis of the neurological disorders. However, the pathogenic mechanisms between COVID-19 and neurological disorders are still unclear. Hence, this review is focused on the genomics and ecology of SARS-CoV2 and elucidated the effects of climatic factors on the progression of COVID-19. This review also critically finds out the vulnerability between COVID-19 and neurological disorders based on the latest research data.

COVID-19 Outbreak: Pathogenesis, Current Therapies, and Potentials for Future Management.

At the end of 2019, a novel coronavirus (CoV) was found at the seafood market of Hubei province in Wuhan, China, and this virus was officially named coronavirus diseases 2019 (COVID-19) by World Health Organization (WHO). COVID-19 is mainly characterized by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) and creates public health concerns as well as significant threats to the economy around the world. Unfortunately, the pathogenesis of COVID-19 is unclear and there is no effective treatment of this newly life-threatening and devastating virus. Therefore, it is crucial to search for alternative methods that alleviate or inhibit the spread of COVID-19. In this review, we try to find out the etiology, epidemiology, symptoms as well as transmissions of this novel virus. We also summarize therapeutic interventions and suggest antiviral treatments, immune-enhancing candidates, general supplements, and CoV specific treatments that control replication and reproduction of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).

Pumpkin (Cucurbita maxima) seeds protect against formaldehyde-induced major organ damages.

Exposures to hazardous chemicals including formaldehyde are harmful to human health. In this study, the authors investigate the protective effects of pumpkin seed oil (PSO) extract against formaldehyde-induced major organ damages in mice. Administration of formaldehyde (FA) caused significant elevation of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum creatinine, etc. Histopathological examinations of liver, kidney, and brain tissues showed the degenerations of those organs. Mice pretreated with PSO extract significantly attenuated the FA-induced elevation of SGOT (39.0 ± 1.30 vs 20.5 ± 0.65 IU/L; FA-group vs PSO treatment group), SGPT (91.8 ± 1.65 vs 51.0 ± 1.29 IU/L), serum creatinine (1.05 ± 0.07 vs 0.65 ± 0.07 IU/L), and preserved the normal histology of organ tissues. The FA-induced elevation of malondialdehyde (MDA) in the brain, liver, and kidneys was suppressed by pretreatment with PSO extract. The extract also attenuated the FA-induced reduction of endogenous antioxidant pools. In vitro phytochemical analyses showed that PSO extract possesses free radical scavenging and total antioxidant activities due to the presence of phenolic and flavonoid compounds. Thus, PSO extract has significant protective effects against FA-induced organ toxicities by scavenging oxidative stress and inhibiting lipid peroxidation.

Pharmacological screening of fenofibrate-loaded solid dispersion in fructose-induced diabetic rat.

OBJECTIVES: Hyperlipidaemia is a common phenomenon in diabetes mellitus. Fenofibrate (FF) is a good candidate for the treatment of lipid abnormalities in patients with type 2 diabetes. But the bioavailability as well as therapeutic efficacy of this drug is limited to its dissolution behaviour. Here, the authors assess the therapeutic efficacy of a newly formulated solid dispersion of fenofibrate (SDF) having enhanced dissolution profiles in contrast to pure FF using fructose-induced diabetic rat model. METHODS: Fructose-induced diabetic rat model was developed to assess the pharmacological efficacy of the formulated SDF, and the results were compared with the effects of conventional FF therapy. KEY FINDINGS: The 14 days treatment showed better improvement in lipid-lowering potency of SDF than pure FF. SDF containing one-third dose of pure FF showed similar effect in terms of triglyceride, total cholesterol and low-density lipoprotein lowering efficacy, whereas increased high-density lipoprotein at same extent. The similar dose of SDF produced more prominent effect than FF. Histological studies also demonstrated the enhanced lipid clearance from liver by SDF than FF that was concordant with the biochemical results. CONCLUSIONS: This newly formulated SDF would be a promising alternative for conventional fenofibrate in treating hyperlipidaemia.

Circadian and sleep dysfunction in Alzheimer's disease.

Alzheimer's disease (AD) is a devastating and irreversible cognitive impairment and the most common type of dementia. Along with progressive cognitive impairment, dysfunction of the circadian rhythms also plays a pivotal role in the progression of AD. A mutual relationship among circadian rhythms, sleep, and AD has been well-recommended. The etiopathogenesis of the disturbances of the circadian system and AD share some general features that also unlock the outlook of observing them as a mutually dependent pathway. Indeed, the burden of amyloid ß (Aß), neurofibrillary tangles (NFTs), neuroinflammation, oxidative stress, and dysfunction of circadian rhythms may lead to AD. Aging can alter both sleep timings and quality that can be strongly disrupted in AD. Increased production of Aß and reduced Aß clearance are caused by a close interplay of Aß, sleep disturbance and raised wakefulness. Besides Aß, the impact of tau pathology is possibly noteworthy to the sleep deprivation found in AD. Hence, this review is focused on the primary mechanistic complexities linked to disruption of circadian rhythms, sleep deprivation, and AD. Furthermore, this review also highlights the potential therapeutic strategies to abate AD pathogenesis.

Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation.

Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1ß and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation.

Antidiabetic, antihyperlipidemic and antioxidant properties of ethanol extract of Grewia asiatica Linn. bark in alloxan-induced diabetic rats.

BACKGROUND: Inspite of introduction of oral hypoglycemic agents, diabetes and its related complications remains to be a major clinical problem. The aim of this study was to investigate the antidiabetic, antihyperlipidemic and antioxidant activities of Grewia asiatica (Linn) stem bark in alloxan induced diabetic rats. METHODS: Diabetes was induced by a single dose of intraperitoneal injection of alloxan (110 mg/kg) in Norwegian Long Evans rats. Ethanol extract of barks from Grewia asiatica (GAE 200 and 400 mg/kg) and metformin (150 mg/kg) were orally administered once daily for 15 days. Blood glucose levels and body weights of rats were measured on 0, 5, 10 and 15 days of oral treatment. At the end of the experiment the rats were sacrificed and blood sample were collected for the measurement of total cholesterol (TC), triglycerides (TG), very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), SGOT and CK-MB. Analysis of liver glycogen content and histopathlogy of pancreas were carried out. In vitro DPPH free radical scavenging activity, total phenolic and total flavonoid content of GAE were also determined. RESULTS: After 15 days of oral administration of GAE at doses of 200 and 400 mg/kg increased survival rate and showed a significant attenuation in blood glucose and lipid profile in diabetic rats. Oral ingestion of GAE significantly reduced the SGOT and CK-MB levels and restored liver glycogen content when compared to diabetic control. The effects of GAE on SGOT, CK-MB and liver glycogen content were dose-dependent. The diabetic rats treated with GAE showed significant improvement in normal cellular population size of islets. Phytochemical screening of GAE revealed the presence of flavonoid, steroid, tannin and phenolic compounds. Total phenolic content was 44.65 ± 3.17 mg of gallic acid equivalent per gm of GAE extract and the total flavonoid content was 39.11 ± 4.65 mg of quercetin equivalent per gm of GAE extract. In DPPH scavenging assay, IC50 values of GAE and ascorbic acid were found 76.45 and 12.50 µg/ml, respectively. CONCLUSION: We demonstrated that ethanol extract of barks from G. asiatica possess glucose, lipid lowering efficacy, restored liver glycogen and protects pancreas from oxidative damage in alloxan-induced diabetic rats. Thus, the results of the present study provide a scientific rationale for the use of G. asiatica in the management of diabetes and its related complications.

Attenuation of Endoplasmic Reticulum Stress-Mediated Liver Damage by Mulberry Leaf Diet in Streptozotocin-Induced Diabetic Rats.

Endoplasmic reticulum stress (ERS) plays a crucial role in the development of insulin resistance and diabetes mellitus. Although antidiabetic use of mulberry leaves (MLs) has been popular due to their many anti-oxidative flavonoid compounds and free radical scavenging effects, ML's effects on ERS in experimental diabetic hepatocyte injury remain unknown. To investigate how ML affect ERS in diabetic liver, Sprague-Dawley (SD) rats were assigned to induce diabetes by a single intraperitoneal injection of streptozocin (STZ; 55 mg/kg) and fed with either normal chow or a diet containing 25% mulberry leaf powder diet (MLD) and examined for 56 days. We observed that MLD improved the rats' morphological and histopathological changes. Levels of ERS markers such as phosphorylated double-stranded RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) and X-box binding protein 1 (XBP1) and the protein expression of glucose regulated protein 78 (GRP78) were significantly higher in the diabetic liver compared to normal liver. MLD for 8 weeks significantly reduced all of these markers. MLD also significantly decreased hepatocyte apoptosis, hepatic macrophage recruitment, cellular infiltration, and CCAAT/enhancer-binding protein homologous protein (CHOP), tumor necrosis factor receptor associated factor 2 (TRAF2), interleukin 1[Formula: see text] (IL-1[Formula: see text]) and sterol regulatory element binding protein isoform 1c (SREBP 1c) levels in diabetic liver. These results may suggest that MLs can preserve hepatic function in experimental diabetes by modulating ERS mediated apoptosis and liver damage.

Antidiabetic and antioxidant activities of ethanolic extract of Semecarpus anacardium (Linn.) bark.

BACKGROUND: Diabetes mellitus is a global health problem and constantly increasing day by day. The number of diabetic people in world is expected to rise to 366 million in 2030. The available drugs for diabetes, insulin or oral hypoglycemic agents have one or more side effects and search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenging for us. The present study was undertaken to investigate the antidiabetic and antioxidant activity of Semecarpus anacardium (Linn.) (abbreviated as SF). METHODS: The antidiabetic activity was determined by using alloxan-induced diabetic rats. After 15 days of treatment, serum biochemical parameters such as TC, TG, LDL, HDL, SGOT and SGPT were estimated. The survival rate, body weight, organ weight, liver glycogen and blood parameters (RBC and Hb) were also measured. The antioxidant activity was measured by DPPH free radical scavenging assay. Phytochemical screening, total phenolic and total flavonoid content were determined by using standard methods. RESULTS: The results showed that the survival rate was 100% in rats of Group SA 400. The effect of extract on blood glucose level in Groups SA 100, SA 200 and SA 400 were dose-dependent throughout the treatment period. No significant changes in organ weight to body weight ratio were observed, liver weights significantly improved in Groups SA 200 and SA 400. The bark extract exhibited significant (p < 0.05) anti-diabetic activity with lowering TC, TG, LDL level dose-dependently and protected liver which may be partially explained by attenuation of SGOT and SGPT levels and increases liver glycogen. The percentage of Hb and RBC counts were negatively correlated with the doses of extracts. In DPPH scavenging assay, IC50 values of SA extract and ascorbic acid were found 72.24 µg/ml and 17.81 µg/ml, respectively. Phytochemical screening showed the presence of steroids, triterpenoids, flavonoids, glycosides, saponins, and tannins that were contribute to biological activity. CONCLUSIONS: These results indicated that stem barks of S. anacardium possess strong anti-diabetic and antioxidant potentials and support traditional medicinal use for the treatment of diabetes mellitus and good source for natural antioxidants.

Development of highly stable nifedipine solid-lipid nanoparticles.

To improve the solubility of the drug nifedipine (NI), highly stabilized solid-lipid nanoparticles (SLNs) of nifedipine (NI-SLNs) were prepared by high pressure homogenization using two phospholipids, followed by lyophilization with individual sugar moieties (four monosaccharides and four disaccharides). The mean particle diameter, polydispersity index (PDI), zeta potential, drug loading, and the encapsulation efficiency of the NI-SLN suspension were determined to be 68.5 nm, 0.3, -62.1 mV, 2.7%, and 97.5%, respectively. In comparison with the NI-SLNs, the NI-SLNs lyophilized with trehalose (NI-SLN-Tre) showed a slight increase in the particle size from 68.5 to 107.7 nm, but the PDI decreased from 0.38 to 0.33, and no significant change in zeta potential was observed. Aqueous re-dispersibility study demonstrated that NI-SLNs lyophilized with trehalose had the maximum concentration (14.7 µg/mL) at 5 min, compared with lyophilized SLNs using other sugars; the use of other sugars also resulted in significant changes in the particle size, PDI, and zeta potential. A trehalose concentration of 2.5% w/v and a two-fold dilution of the SLN suspension were found to be the best conditions for lyophilization. Data from lyophilized SLNs using differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, and scanning electron microscopy indicated eventual transformation of NI-SLN-Tre from a crystalline to an amorphous state during the homogenization process. Finally, a stability study was performed with NI-SLN-Tre for up to 6 months at 30°C and 65% relative humidity, with no significant deterioration observed, suggesting that trehalose might be a useful cryoprotectant for NI-SLNs.

Antidiabetic and hypolipidemic effects of different fractions of Coccinia cordifolia L. on normal and streptozotocin-induced diabetic rats.

The present study was carried out to observe the antidiabetic and hypolipidemic effects of petroleum-ether, ethyl acetate and chloroform fractions isolated from ethanolic extract of the leaves of Coccinia cordifolia Linn. (150 mg/kg body weight) on normal and streptozotocin (STZ)-induced diabetic rats for one day experiment. Single doses (150 mg/kg, i.p.) of C. cordifolia extracts were given to normal and diabetic rats. The fasting blood glucose (FBG), serum triglyceride (TG) and serum total cholesterol (TC) levels were investigated in normal and STZ-diabetic rats on 0, 1, 2, 3, 6, 10, 16, and 24th hours. In normoglycemic rats the pet-ether and ethyl acetate fractions of C. cordifolia reduced blood glucose level significantly (39.66% and 40.68% at 16th and 24th hour respectively). In the STZ-diabetic rats pet-ether and ethyl acetate fractions also reduced blood glucose level significantly (50.39% and 50% at 10th and 24th hour respectively). Ethyl acetate fraction is most effective which reduced total cholesterol level by 31.04% and 36.69% in normal and STZ-diabetic rats respectively. Ethyl acetate fraction reduced triglyceride level by 43.82% and 42.01% in normal and STZ-diabetic rats respectively. Our results indicate that pet-ether and ethyl acetate fractions of C. cordifolia have potentiality against diabetes.

Oral glucose tolerance test (OGTT) in normal control and glucose induced hyperglycemic rats with Coccinia cordifolia l. and Catharanthus roseus L.

The aim of this study is to investigate the hypoglycemic effects of petroleum ether, chloroform and ethyl acetate fractions isolated from ethanolic extracts of Coccinia cordifolia and Catharanthus roseus on normal control and orally glucose-induced hyperglycemic rats. Single doses (150 mg/kg) of different fractions of C. cordifolia and C. roseus extracts were intraperitonelly administered. The serum blood glucose level was obtained by pricking the tail vein using glucometer at time 0, 30, 60, 90, 150 and 270 minutes. In the orally glucose induced hyperglycemic rats, chloroform-coccinia (CHCl3-CC) fraction showed maximum reduction of blood glucose level by 21.94% on 60 minute of the experiment. On the other hand maximum reduction (p<0.05) of 17.92% was observed for petroleum ether-catharanthus (PET-CR) on 30 minute of the experiment. Metformin HCl was used as standard drug. Our results indicate that the CHCl3-CC fraction is relatively more potent than other fractions of C. cordifolia. Similarly the PET-CR is found to be better than other fractions of catharanthus. Phytochemical screening test results showed that chloroform fraction of C. cordifolia contain saponins and flavonoids compounds, which are known to be hypoglycemic. On the other hand petroleum ether fraction of C. roseus contains tannins, flavonoids and alkaloid compounds produced varying degree of blood sugar reduction. On the pharmacological point of view C. cordifolia and C. roseus appears to be a valuable plant, which can be useful, at least as an adjunct, in the therapy of diabetes.

Effect of starch 1500 as a binder and disintegrant in lamivudine tablets prepared by high shear wet granulation.

High shear wet granulation is a preferred manufacturing method of tablets. It allowed for rapid production of compressible granulations. The resultant granulation characteristics depend on a combination of formulation properties and processing parameters. Fully pregelatinized starches are currently being used as binders in wet granulated formulations. But due to the gelatinization, much of the disintegration properties are lost. Partially pregelatinized starches (starch 1,500) have a mixture of properties of both native and fully gelatinized starches; made them useful as both a binder and a disintegrant in wet granulated formulations. Starch 1,500 performed as an excellent binder producing a granulation that was compressible and produced lamivudine tablets of improved hardness and friability compared with those prepared with povidone. The formulation of lamivudine tablets with starch 1,500 exceeded the disintegration and dissolution performance of the povidone formulation that utilized a super disintegrant. High shear wet granulation is also well suited for the use of partially pregelatinized starches.

Simultaneous high-performance liquid chromatographic determination of atenolol and amlodipine in pharmaceutical-dosage form.

A simple, rapid and precise method is developed for the quantitative simultaneous determination of atenolol and amlodipine in a combined pharmaceutical-dosage form. The method is based on High Performance Liquid Chromatography (HPLC) on a reversed-phase column, shim-pack CLC, ODS (C18), 4.6 mmx25 cm & 0.5 mm, using a mobile phase of ammonium acetate buffer (the pH was adjusted to 4.5+/-0.05 with glacial acetic acid), acetonitrile and methanol (35::30:35 v/v). The buffer used in the mobile phase contains ammonium acetate in double-distilled water. The chromatographic conditions are- flow rate of 1.5 ml/min, column temperature at 40 degrees C and detector wavelength of 237 nm. Both the drugs were well resolved on the stationary phase and the retention times were around 1.5 minute for atenolol and 3.4 minute for amlodipine. The method was validated and shown to be linear for atenolol and amlodipine. The correlation coefficients for atenolol and amlodipine are 0.999963 and 0.999979, respectively. The relative standard deviations for six replicate measurements in two sets of each drug in the tablets is always less than 2% and mean % error of active recovery not more than +/-1.5%. The method was validated for precision and accuracy. The proposed method was successfully applied to the pharmaceutical dosage forms containing the above-mentioned drug combination without any interference by the excipients.

Comparative effects of pranidipine with amlodipine in rats with heart failure.

The aim of the present study was to compare the cardioprotective properties of long-acting calcium channel antagonist pranidipine with amlodipine in rat model of heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were randomized for the oral administration of low-dose amlodipine (1 mg/kg/day), high-dose amlodipine (5 mg/kg/day), pranidipine (0.3 mg/kg/day) or vehicle (0.5% methylcellulose). After oral administration for 1 month, the animals underwent echocardiography and hemodynamic analysis. Histopathology, immunohistochemistry, and Western immunoblotting were carried out in the heart samples. Both pranidipine and high-dose amlodipine increased survival rate. Although the heart rate did not differ among the four groups, left ventricular end-diastolic pressure was significantly decreased and +/-dP/dt was increased in the pranidipine- and high-dose amlodipine-treated rats, but not in low-dose amlodipine-treated rats. In comparison to amlodipine treatment, pranidipine treatment significantly reduced myocyte size and central venous pressure. Furthermore, both pranidipine and high-dose amlodipine treatment significantly reduced myocardial protein levels of atrial natriuretic peptide and inducible nitric oxide synthase, whereas pranidipine only significantly decreased tumor necrosis factor-alpha, and improved sarcoplasmic reticulum Ca2+ ATPase2 protein levels. We conclude that pranidipine ameliorates the progression of left ventricular dysfunction and cardiac remodeling in rats with heart failure after autoimmune myocarditis in a lower dose when compared to amlodipine and which may be a clinically potential therapeutic agent for the treatment of heart failure.

Effects of angiotensin-II receptor blocker candesartan cilexetil in rats with dilated cardiomyopathy.

We examined effects of an angiotensin-II receptor blockers, candesartan cilexetil, in rats with dilated cardiomyopathy after autoimmune myocarditis. Candesartan cilexetil showed angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Twenty-eight days after immunization, surviving Lewis rats were divided into four groups and given candesartan cilexetil at 0.05 mg/kg, 0.5 mg/kg or 5 mg/kg per day (Group-C0.05, n = 15, Group-C0.5, n = 15 and Group-C5, n = 15, respectively) or vehicle alone (Group-V, n = 15). After oral administration for 1 month, the left ventricular end-diastolic pressure and heart weight/body weight ratio were lower in Group-C0.05 (13.3+/-1.1 mmHg and 3.7+/-0.2 g/kg, respectively), in Group-C0.5 (8.0+/-0.9 mmHg and 3.3+/-0.1 g/kg, respectively) and in Group-C5 (5.5+/-1 mmHg and 3.1+/-0.1 g/kg, respectively) than in Group-V (13.5+/-1.0 mmHg and 3.8+/-0.2 g/kg, respectively). The area of myocardial fibrosis was also lower in Group-C0.05 (25+/-3%), in Group-C0.5 (20+/-3%), and in Group-C5 (12+/-1%) than in Group-V (32+/-4%). Furthermore, expressions of transforming growth factor-beta1 and collagen-III mRNA were suppressed in Group-C0.05 (349+/-23% and 395+/-22%, respectively), Group-C0.5 (292+/-81% and 364+/-42%, respectively) and in Group-C5 (204+/-63% and 259+/-33%, respectively) compared with those in Group-V (367+/-26% and 437+/-18%, respectively). These results suggest that candesartan cilexetil can improve the function of inefficient heart.