Solid Dispersion of Curcumin as Polymeric Films for Bioenhancement and Improved Therapy of Rheumatoid Arthritis.

PURPOSE: The aim of our study was development of advanced third generation Curcumin self microemulsifying composition solid dispersion (Cur SMEC-SD) with high drug loading, improved stability, rapid in-vitro dissolution and enhanced bioavailability for improved therapy of rheumatoid arthritis. METHOD: The Cur SMEC-SD comprising polymers (KollidonVA64[KVA], Eudragits, HPMC and Soluplus) and self microemulsifying composition of surfactant:co-surfactant:oil were coated onto rapidly disintegrating inert tablet core. SDs evaluated for stability, in-vitro release and bioenhancement. RESULTS: Cur SMEC-SDs exhibited high Cur loading of 45% w/w and microemulsion formation with globule size (~100 nm) irrespective of polymers. Among the polymers, SD with KVA revealed exceptionally low contact angle (7°C) and rapid in-vitro release (t50%-6.45 min). No crystallization was evident as confirmed by SEM, DSC and XRD and is attributed to SMEC aided solubilization/amorphisation, and interaction of KVA with Cur seen in the FTIR spectra. Stability was confirmed as per ICH guidelines. Remarkable bioenhancement with Cur SMEC-SD was confirmed by the > four fold and a two fold compared to Cur and Cur-SD without SMEC respectively. High efficacy ~ 80% compared to Indomethacin, seen with rheumatoid arthritis (RA) induced rats coupled with no adverse toxicity. CONCLUSION: The advanced third generation Cur SMEC-SD presents a practical technological advancement and suggests Cur SMEC-SD as promising alternative for RA therapy.

Effect of Viscum articulatum Burm. (Loranthaceae) in Nω-nitro-L-arginine methyl ester induced hypertension and renal dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum articulatum Burm. is used traditionally in Chinese medicine for treating hypertension. AIM OF THE STUDY: The present study was designed to evaluate the antihypertensive activity of the methanolic extract of Viscum articulatum (MVA) against N(ω)-nitro-L-arginine methyl ester (L-NAME) induced hypertension in rats. MATERIALS AND METHODS: Six groups of rats were investigated for 4 weeks as normal control, L-NAME (40 mg/kg/day), L-NAME+enalapril (15 mg/kg/day), L-NAME+L-arginine (100 mg/kg/day), L-NAME+MVA (200 mg/kg/day) and L-NAME+MVA (400 mg/kg/day) for four weeks. The systolic blood pressure (SBP) and heart rate (HR) were measured weekly throughout the experimental period. The urine electrolytes concentration, cardiac mass index, serum nitrate/nitrite (NO(x)) level, serum creatinine level and lipid profile were determined. RESULTS: Treatment with MVA (200 and 400 mg/kg) or enalapril delayed the rise in SBP produced by administration of L-NAME. None of the treatments had a significant effect on the depression of the serum NO(x) level caused by L-NAME. The serum creatinine and total cholesterol concentrations were elevated upon administration of L-NAME, and this elevation was prevented by MVA co-administration. The urine volume and urine potassium ion level were depressed by L-NAME administration and this effect being inhibited in MVA and enalapril groups. There was no cardiac hypertrophy and HR change after 28 day of L-NAME administration. CONCLUSION: We conclude that MVA may have an antihypertensive effect in the NO deficient type of hypertension, which may be attributed to its diuretic, nephroprotective and hypolipidemic actions.

Oleanolic acid prevents glucocorticoid-induced hypertension in rats.

The present study was designed to evaluate the antihypertensive activity of oleanolic acid isolated from Viscum articulatum, Burm. (Loranthaceae) in glucocorticoid (dexamethasone)-induced hypertension in rats and to propose a probable mechanism of action for this effect. Male Wistar rats (300-350 g) received dexamethasone (20 µg/kg/day s.c.) or saline (vehicle) for 10 days. In a prevention study, the rats received oleanolic acid (60 mg/kg i.p.) for 5 days, followed by dexamethasone or saline for 10 days. During this period the systolic blood pressure and body weight were evaluated on alternate days. At the end of the experiment, the weight of the thymus gland, plasma nitrate/nitrite (nitric oxide metabolites) concentration and cardiac lipid peroxidation value were determined. Oleanolic acid (60 mg/kg i.p.) significantly prevented a rise in the systolic blood pressure and cardiac lipid peroxidation level after administration of dexamethasone (p < 0.01 and p < 0.05, respectively) without showing any significant effect on the dexamethasone-induced change in body and thymus weights. The decrease in concentration of plasma nitrate/nitrite due to dexamethasone was prevented significantly in the group treated with oleanolic acid (p < 0.05). These findings suggest that oleanolic acid (60 mg/kg i.p.) prevents dexamethasone-induced hypertension in rats, which may be attributed to its antioxidant and nitric oxide releasing action.