Neurodegenerative Shielding by Curcumin and Its Derivatives on Brain Lesions Induced by 6-OHDA Model of Parkinson's Disease in Albino Wistar Rats.

Study was undertaken to evaluate the neurodegenerative defending potential of curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) on 6-hydroxydopamine-(6-OHDA) induced Parkinsonism model in rats. Curcuminoids were administered (60 mg/kg, body weight, per oral) for three weeks followed by unilateral injection of 6-OHDA on 22nd day (10 µg/2 µL) into the right striatum leading to extensive loss of dopaminergic cells. The behavioral observations, biochemical markers, quantification of dopamine (DA), DOPAC, and HVA followed by dopamine (D(2)) receptor binding assay and tyrosine hydroxylase (TH, using immunohistochemistry) were evaluated using HPLC after three weeks of lesion. Pretreated animals showed significant protection against neuronal degeneration compared to lesion animals by normalizing the deranged levels of biomarkers and showed the potency in the order CUR > DMC > BDMC. The same order of effectiveness was observed in D(2) receptors binding assay and TH immunohistochemistry study. We conclude that curcuminoids appear to shield progressive neuronal degeneration from increased oxidative attack in 6-OHDA-lesioned rats through its free radical scavenging mechanism, and DA, DOPAC, and HVA enhancing capabilities in the sequence of efficacy CUR > DMC > BDMC. Further, curcuminoids may have potential utility in treatment of many more oxidative stress-induced neurodegenerative disorders.

Formulation and evaluation of delayed-onset extended-release tablets of metoprolol tartrate using hydrophilic-swellable polymers.

In view of the circadian rhythm of cardiovascular diseases, a delayed-onset extended-release (DOER) formulation of metoprolol tartrate (MT) was prepared. This was achieved through dissolution-guided optimization of the proportion of Methocel K4M and Methocel K15M. Core erosion ratio was greater than 50 %, thereby showing steady release of the drug after the lag time until complete dissolution. Optimized formulation produced a lag phase of 6 h followed by complete release of 98.7 ± 2.1 % in 24 h. Water uptake study revealed that Methocel K15M has lower water uptake (30 ± 1 %) than Methocel K4M (40 ± 2 %) after 24 h. Axial swelling of polymers was higher than swelling in the radial direction. Drug-polymer interaction study precludes any interaction between drug and polymer. Such a drug delivery system may provide a viable alternative for effective management of hypertension and other related disorders. This work also proposes an approach to attain DOER for a hydrophilic drug by using a hydrophilic swellable polymer in press coat.

Development and evaluation of matrix type transdermal patch of ethinylestradiol and medroxyprogesterone acetate for anti-implantation activity in female Wistar rats.

BACKGROUND: Medroxyprogesterone acetate (MPA), which increases high-density lipoprotein level, has not been used as a progestin in combination with estrogen in a transdermal patch to date. The aim of the research was to develop and evaluate a matrix-type transdermal drug delivery (TDD) system of a combination of ethinylestradiol (EE) and MPA for interception. STUDY DESIGN: The transdermal patch of EE and MPA was prepared using various film-forming polymers with and without n-dibutyl phthalate as plasticizer and with glycerol and sodium lauryl sulphate as penetration enhancer. All formulations were assayed using UV spectrophotometer by Vierordt's equation for EE and MPA. RESULTS: The percentage cumulative release of F6 (optimized formulation) named as 'AGARPRU' was found to be 99.94%±1.25% and 69.99%±1.02% (mean±SD) through rat skin and 92.69%±2.22% and 53.51%±2.11% (mean±SD) through cadaver skin for EE and MPA, respectively. Pharmacodynamic studies of 'AGARPRU' in female Wistar rats showed 100% anti-implantation activity. The in vivo results showed prolonged T(max) of 36 h for both EE and MPA after transdermal administration compared to oral route (2 h). Moreover, the area under the curve of EE and MPA revealed an increase in bioavailability after transdermal administration as compared to oral route. CONCLUSION: These findings suggested that TDD formulation aimed for postcoital antifertility activity has been successfully developed in female Wistar rats.

Curcumin prevents experimental diabetic retinopathy in rats through its hypoglycemic, antioxidant, and anti-inflammatory mechanisms.

PURPOSE: The purpose of this study was to evaluate the therapeutic potential of oral curcumin (1 g/kg body weight of rat) in the prevention and treatment of streptozotocin-induced diabetic retinopathy in Wistar albino rats. METHODS: The treatment was carried out for a period of 16 weeks in diabetic rats and evaluated for hyperglycemic, antioxidant (superoxide dismutase, catalase, and glutathione), and inflammatory parameters (tumor necrosis factor-α, vascular endothelial growth factor). Rat fundus was observed weekly to see any visible changes in the retina, such as tortuosity and dilation of retinal vessels. Histological changes were evaluated by transmission electron microscopy. RESULTS: Treatment with curcumin showed significant hypoglycemic activity compared with the diabetic group. Retinal glutathione levels were decreased by 1.5-fold, and antioxidant enzymes, superoxide dismutase and catalase, showed >2-fold decrease in activity in the diabetic group; on the other hand, curcumin positively modulated the antioxidant system. Proinflammatory cytokines, tumor necrosis factor-α and vascular endothelial growth factor, were elevated >2-fold in the diabetic retinae, but prevented by curcumin. Transmission electron microscopy showed degeneration of endothelial cell organelles and increase in capillary basement membrane thickness in diabetic retina, but curcumin prevented the structural degeneration and increase in capillary basement membrane thickness in the diabetic rat retinae. CONCLUSION: Based on the above results, it may be concluded that curcumin may have potential benefits in the prevention of retinopathy in diabetic patients.

Therapeutic potential of Curcuma longa, the golden spice of India, in drug discovery for ophthalmic diseases.

BACKGROUND: Curcuma longa is among the most commonly used spices in India and other Asian countries. The herb has also been used in Ayurveda and other traditional systems of medicine for the prevention and treatment of a variety of ailments. Curcuminoids are the major chemical constituents of C. longa that are of medicinal importance. Today, a large body of scientific evidence exists to indicate potential therapeutic benefits of C. longa. Several preclinical and clinical studies have investigated the pharmacological properties of C. longa and results indicate strong therapeutic potential for anti-inflammatory, antioxidant, antibacterial, anticancer and many other properties. OBJECTIVE: This review summarizes the scientific evidences showing possible benefits of C. longa in a variety of ophthalmic diseases. CONCLUSION: Although the putative mechanism(s), molecular targets and range of therapeutic applications have been researched widely, further investigations are needed to explore the true therapeutic potential and future of curcuminoids as novel drug molecules in ophthalmic diseases.

Development of atropine sulphate nasal drops and its pharmacokinetic and safety evaluation in healthy human volunteers.

INTRODUCTION: The increased use of organophosphate (OP) insecticides and the ever increasing possibility of terror groups using nerve agents underscore the need to develop effective and safe antidotes against OP poisoning. While intramuscular administration of nerve gas antidotes like atropine sulphate has certain lacunae, intravenous route is neither practical nor feasible in the field conditions for mass casualties. The objective was to develop a novel atropine sulphate nasal drop formulation, evaluate and characterize it using scintigraphy and to carry out safety-efficacy study in human volunteers with a view to obtain early pharmacological effects in comparison to the existing options, particularly the conventional intramuscular route. METHODS: Permeability studies were done using atropine sulphate solution containing variable amount of chitosan. Radiometric method was developed for scintigraphy studies while standard spectroscopy was used for the quantification of atropine sulphate in fluids. Concentration of atropine sulphate in nasal drops to produce therapeutic concentration in blood was calculated. Six volunteers (age range 18-53 years) were administered the formulation delivering 6mg of atropine sulphate each. Bioavailability and atropinization were noted serially. RESULTS: Based on the results of in vitro, human scintigraphy and analytical data, 1% atropine sulphate-0.5% chitosan was chosen as the final nasal formulation. Human bioavailability curve was created which showed that the therapeutic concentration of the drug in blood was reached within 5min with nasal drops suggesting that drug delivery through the nasal route is significantly better than the intramuscular route. Unpaired t-test between the means of baseline value of heart rate and that of each time interval showed that increase in heart rate of all the volunteers became significant at 15min (P<0.01) and extremely significant at 30min (P<0.001). Correlation was evident from 5min (c>0.7). Pupil diameter showed maximal increase at 30min (P<0.01). CONCLUSIONS: This novel product, 1% atropine sulphate-0.5% chitosan nasal drops might be a safe and efficacious emergency treatment of organophosphorous poisoning with several advantages over the present management, including early atropinization and capability of mass treatment in least amount of time.

Oculohypotensive effects of foeniculum vulgare in experimental models of glaucoma.

PURPOSE: Evaluation of oculohypotensive activity of single drop application of aqueous extract of Foeniculum vulgare in experimental models of glaucoma. METHODS: The evaluation of oculohypotensive activity of Foeniculum vulgare was done in rabbits with normal intraocular pressure (IOP) and with experimentally elevated IOP. The experimental increase in IOP was achieved using water loading and steroid induced glaucoma models. RESULTS: The aqueous seed extract of Foeniculum vulgare exhibited 17.49, 21.16 and 22.03% reduction of intraocular pressure (IOP) in normotensive rabbits at 0.3%, 0.6% and 1.2% (w/v) concentrations respectively. The 0.6% concentration was further evaluated in acute and chronic models of glaucoma. A maximum mean difference of 31.20% was observed between vehicle treated and extract treated eyes in water loading model while a maximum mean IOP lowering of 31.29% was observed in steroid induced model of glaucoma. CONCLUSIONS: The aqueous extract of Foeniculum vulgare possesses significant oculohypotensive activity, which was found to be comparable to that of timolol. Further investigations into the mechanism of action, possible toxicity and human clinical trials are warranted before the Foeniculum vulgare finds place in the arsenal of antiglaucoma drugs prescribed by physicians.

The anti-inflammatory effects of Curcuma longa and Berberis aristata in endotoxin-induced uveitis in rabbits.

PURPOSE: To investigate the anti-inflammatory effect of topical application of Curcuma longa (C. longa) and Berberis aristata (B. aristata) aqueous extracts on experimental uveitis in the rabbit. METHODS: Anterior uveitis was induced in rabbits by intravitreal injection of lipopolysaccharide from Escherichia coli after pretreatment with C. longa and B. aristata aqueous extracts. Subsequently, the anti-inflammatory activity of C. longa and B. aristata was evaluated by grading the clinical signs and histopathologic changes and estimating the inflammatory cell count, protein, and TNF-alpha levels in the aqueous humor. RESULTS: The anterior segment inflammation in the control group was significantly higher than in both the extract-treated groups, as observed by clinical and histopathologic grading. The inflammatory cell count in the control group was 30.75 +/- 7.33 x 10(5) cells/mL, whereas it was 2.39 +/- 0.59 x 10(5) (P < 0.001 vs. control) and 11.56 +/- 2.44 x 10(5) (P = 0.001 vs. control) cells/mL in the C. longa- and B. aristata-treated groups, respectively. The protein content of the aqueous humor was 18.14 +/- 4.98, 3.16 +/- 0.55 (P < 0.001 vs. control), and 8.24 +/- 1.42 (P < 0.01 vs. control) mg/mL in the control, C. longa-, and B. aristata-treated groups, respectively. The aqueous TNF-alpha level in the control group was 976.29 +/- 66.38 pg/mL and was 311.96 +/- 28.50 (P < 0.0001 vs. control) and 654.09 +/- 47.66 (P < 0.001vs. control) pg/mL in the C. longa- and B. aristata-treated groups, respectively. CONCLUSIONS: Topical instillation of aqueous extracts of C. longa and B. aristata showed potent anti-inflammatory activity against endotoxin-induced uveitis in rabbits.

Therapeutic potential of green tea: a new horizon in drug discovery.

Worldwide, tea is one of the most widely consumed beverages. Green tea consumption is especially popular in China, Japan and other Asian countries. It has been found to be rich in polyphenolic compounds, of which catechins are the major constituents. A large number of clinical and preclinical studies have explored its pharmacologic activities. It holds promise as an antioxidant, anti-inflammatory, antibacterial, antiarteriosclerotic, cardioprotective, neuroprotective and anticarcinogenic agent, to name a few. This review summarizes the pharmacodynamics and pharmacokinetics of green tea polyphenols and explores their future as novel drugs for both health and disease conditions.

Drug utilization study in dermatology in a tertiary hospital in Delhi.

The present study was undertaken to describe patterns of dermatological drug utilization in a tertiary hospital in Delhi by measuring WHO delineated drug use indicators. Six hundred and six prescriptions of dermatology out-patients were analyzed and the data collected were used to evaluate the following drug use indicators: average number of drug per prescription, average consultation time, percentage of drugs prescribed by generic name, percentage of encounters with an antibiotic prescribed, percentage of encounters with an injection prescribed and percentage of drug prescribed from the essential drugs list or formulary. The average number of drugs per prescription +/- SD was found to be 2.6 +/- 1.2, average consultation time +/- SD was 4.4 +/- 2.6 minutes, percentage of drug prescribed by generic name was 6.98, percentage of encounters with an antibiotic and injection prescribed were 46.86 and 6.76 respectively and 23% of the total drugs prescribed were from Delhi State Essential Drugs Formulary.