Clerodendrum serratum extract attenuates production of inflammatory mediators in ovalbumin-induced asthma in rats.

In the present study, ethanolic extract of Clerodendrum serratum roots was investigated for its potential to reverse some features of bronchial asthma in ovalbumin-induced murine model of asthma. Clerodendrum serratum commonly called bharangi, (family Solanaceae) is a well-known anti-allergic drug in Asian folk system of medicines. In the present work, pharmacological studies are done to provide scientific evidence for therapeutic potential of plant in allergic asthma. Asthma was induced in experimental rats with allergen suspension of ovalbumin and aluminum hydroxide followed by treatment with dexamethasone (2.5 mg/kg, po) or C. serratum root extract (0.53 and 5.3 mg/kg, b. w., po). Biomarkers of inflammatory response including cell counts, immunoglobulin E, cytokines such as interleukin (IL) -4, -5, -1ß, tumor necrosis factor-α (TNF-α), leukotriene (LTD-4), and nitrite concentration in blood as well as bronchial (BAL) fluid were tested. Lung functions in asthmatic and treated animals were evaluated as breathing rate and tidal volume. Treatment with C. serratum extract markedly (p < 0.001, p < 0.01, and p < 0.05) diminished infiltration of inflammatory cells, IgE, cytokines, and nitrites in blood serum and bronchial fluid. Improvement in lung functions (p < 0.05) of asthmatic animals after CSE treatment also supports our findings. Results of the study suggest therapeutic potential of C. serratum in allergic asthma that can be related to ability of plant to attenuate response of inflammatory cells and thereby, production of inflammatory and proinflammatory cytokines in airways.

Antithrombocytopenic and immunomodulatory potential of metabolically characterized aqueous extract of Carica papaya leaves.

CONTEXT: Carica papaya Linn. (Caricaceae) leaf (CPL) juice has long been traditionally used in ethnomedicine for dengue fever. OBJECTIVE: The study examines the effects of standardized CPL aqueous extract (SCPLE) on platelet count, extramedullary haematopoiesis (EMH), and immunomodulation in cyclophosphamide (CP)-induced animal model of thrombocytopenia. MATERIALS AND METHODS: The extract was analyzed for myricetin, caffeic acid, trans-ferulic acid, and kaempferol using HPTLC for standardization followed by UPLC-qTOF/MS fingerprinting for metabolite signature. The effects of SCPLE (50 and 150 mg/kg p.o.) on proliferative response of platelet count and total leucocyte count (TLC) were observed up to 14 days in Wistar rat. However, delayed-type hypersensitivity (DTH), haemagglutination titre (HT), and in vivo carbon clearance were examined as immunomodulatory parameters in albino mice at 150 mg/kg p.o. against CP. RESULTS: The quantitative HPTLC estimation of SCPLE showed the presence of myricetin, caffeic acid, trans-ferulic acid, and kaempferol up to 280.16 ± 5.99, 370.18 ± 6.27, 1110.86 ± 2.97, and 160.53 ± 2.48 (µg/g), respectively. Twenty-four metabolites were identified using UPLC-qTOF/MS. Oral administration of SCPLE (150 mg/kg) in thrombocytopenic rats exhibited significant (p < 0.01) increase in thrombocytes (1014.83 × 103 cells/mm3), DTH response (0.16 ± 0.004), and phagocytic index (63.15% increase) as compared to CP-induced thrombocytopenia group. Histopathological studies showed minimal fibrosis in spleen histology. DISCUSSION AND CONCLUSIONS: Results suggest CPL can mediate the release of platelets providing the means for the treatment and prevention of dengue.

Development and evaluation of solid dispersion of spironolactone using fusion method.

INTRODUCTION: Solubility and dissolution of a poor water-soluble drug are the two major barriers for formulation scientists in development of drug delivery. Many of the potent drugs do not show the therapeutic effects due to solubility issues but may show toxicity issues when used in high doses. Solid dispersion (SD) technology is an excellent tool for enhancing the solubility and dissolution and hence related bioavailability. MATERIALS AND METHODS: SD of spironolactone (SPL) was developed using an inert carrier polyethylene glycol 4000 (PEG 4000) by the conventional fusion method and characterized for various characterization parameters. RESULTS: Solubility of pure drug and SD of SPL in water was found to be 23.54 ± 1.75 µg/mL and 61.73 ± 1.26 µg/mL, respectively. The maximum cumulative percentage release from pure drug, SPL marketed product (tablet), physical mixture, and SPL SD at 60 min was 27.25 ± 1.83%, 35.64 ± 3.65%, 47.72 ± 2.45%, and 74.24 ± 3.25%, respectively in 0.1 N HCl. CONCLUSIONS: SD of SPL was developed successfully. The solubility of SPL SD was found to be significantly increased (P < 0.05) as compared to SPL active pharmaceutical ingredient (API) and physical mixture of PEG 4000 and SPL. The current study indicated that SD of SPL was a better option for enhancing solubility of a poorly soluble therapeutic agent.

Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy.

Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25 mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia ((§§§)p < 0.001) was observed in all STZ-treated groups except those received insulin (2 U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy.

Enhanced dissolution and bioavailability of grapefruit flavonoid Naringenin by solid dispersion utilizing fourth generation carrier.

CONTEXT: Naringenin (NRG), the aglycone flavonoid present in grapefruits, possesses anti-inflammatory, anti-carcinogenic, anti-lipid peroxidation and hepato-protective effects. However, it is poorly soluble in water and exhibits slow dissolution after oral ingestion, thus restricting its therapeutic efficacy. OBJECTIVE: With the aim to enhance the dissolution rate and oral bioavailability of NRG, solid dispersion technique has been applied using Soluplus® as carrier. METHODS: Solid dispersions of NRG were prepared by solvent evaporation and kneading methods using various ratios (1:4, 3:7, 2:3 and 1:1) of NRG:Carrier. Characterization of the optimized formulations was performed using Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The in vivo behavior of the optimized formulations was also investigated in Wistar Albino rats. RESULTS: NRG solid dispersion showed a significantly higher solubility and drug dissolution rate than pure NRG (p < 0.001) and it followed the Higuchi model. Among the different methods employed for the preparation of solid dispersions, solvent evaporation showed better drug release profile. DSC analysis indicated reduced crystallinity of NRG as no discrete peaks of NRG were observed. This was further substantiated by XRD analysis. Furthermore, area under the drug concentration time-curve (AUC) of NRG from solid dispersion revealed a significant increase in NRG absorption compared to NRG alone. CONCLUSION: Based on these results, it was concluded that solid dispersion technique markedly enhances the in vitro drug release and in vivo behavior of the grapefruit flavonoid NRG.

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization, in vitro and in vivo evaluation.

Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed self-nanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50 nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p < 0.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC(0-24)) of NRG from SNEDDS formulation revealed a significant increase (p < 0.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.

Scintigraphic Evaluation of Decontamination Lotion for Removal of Radioactive Contamination From Skin.

OBJECTIVE: Skin contamination is one of the most likely risks after accidental or occupational radiological accidents. Using scintigraphy, we assessed a topical lotion for its decontamination efficacy (DE) after exposure with short-lived medical radioisotopes technetium Tc 99m (99mTc) and thallium 201Tl (201Tl). METHODS: Using 99mTc (300 ± 5 µCi/100 µl) and 201Tl (100 ± 5 µCi/100 µl), the thoracoabdominal region (shaved skin) of Sprague Dawley rats and human tissue equivalent were contaminated and then decontaminated using cotton swabs soaked in formulated lotion at different time intervals. Static counts were recorded and calculated for DE. Histologic examination was performed on the animal model. RESULTS: The DE of the formulation for 99mTc and 201Tl was 85% ± 5 and 88% ± 2, respectively. The prepared formulation effectively removed the radionuclides from the tissue surface. CONCLUSIONS: The formulated lotion assisted in the effective removal of radiocontaminants by decontaminating the radionuclides. Moreover, minimal and easily manageable radioactive waste was generated by this process. Further investigation regarding the infusion of formulated lotion into ready-to-use skin wipes for self-decontamination may be useful for mass casualty scenarios. (Disaster Med Public Health Preparedness. 2014;0:-).

Comparative evaluation of the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods.

The aim of the present study was to assess the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods. Aqueous and ethanol extracts of Pterocarpus marsupium heartwood were prepared by conventional methods (infusion, decoction, maceration and percolation) and non conventional methods, such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE). The crude aqueous extracts were administered orally to both normal and alloxan induced male albino rats (Sprague-Dawley strain). The experimental set up consisted of 48 male albino rats divided into 6 groups: Normal control, diabetic control (sterile normal saline, 1 ml/100 g body weight), standard (gliclazide, 25 mg/1000g of body weight), groups 4-6 (crude aqueous percolation, optimized UAE and MAE extract, 250 mg/1000g of body weight). In acute treatment, the reduction of blood glucose level was statistically significant with the oral administration of UAE and percolation aqueous extracts to the hyperglycemic rats. In sub-acute treatment, the UAE aqueous extract led to consistent and statistically significant (p<0.001) reduction in the blood glucose levels. There was no abnormal change in body weight of the hyperglycemic animals after 10 days of administration of plant extracts and gliclazide. This study justifies the traditional claim and provides a rationale for the use of Pterocarpus marsupium to treat diabetes mellitus. The antidiabetic activity of Pterocarpus marsupium can be enhanced by extracting the heartwood by non conventional method of UAE.

Skin decontamination cream for radiological contaminants: Formulation development and evaluation.

BACKGROUND: Increased use of the radioactive materials in the field of research, medical, nuclear power plant, and industry has increased the risk of accidental exposure. Intentional use of the radioisotopes by terrorist organizations could cause exposure/contamination of a number of the population. In view of the accidental contamination, there is a need to develop self-usable decontamination formulations that could be used immediately after contamination is suspected. MATERIALS AND METHODS: Present work was planned to optimize and develop self-usable radiation decontamination cream formulation. Various pharmaceutical parameters were characterized. (99m)Tc-sodium pertechnetate was used as radiocontaminant. Static counts were recorded before and after decontamination using single photon emission computed tomography. RESULTS: Decontamination efficacy of the cream was found to be 42% ± 3% at 0-0.5 h after the exposure. Primary skin irritancy test was satisfactory as no erythema or edema was observed visually after 2 weeks of the formulation application. CONCLUSION: The decontamination studies proved the potential of EDTA to remove the radiological contaminants effectively.