Effect of Cyclodextrin Garcinol Complex on Pressure Overload- Induced Cardiotoxicity and Cardiac Hypertrophy by Aortic Stenosis in Rats

Background: Garcinol is a polyisoprenylated benzophenone derived from rinds of fruit of Garcinia species namely Garciniaindica (common name ‘Kokum’) and Garcinia cambogia (common name ‘Gombogee’). Garcinol is not stable and has poor bioavailability which can be improved by complexing garcinol with cyclodextrin (cyclodextringarcinol complex). Objective: The objective of the present study was to investigate effect of cyclodextrin-garcinol complex (20 mg/kg/) on pressure overloadinduced cardiotoxicity and cardiac hypertrophy by aortic stenosis in rats. Methods: Male Wistar rats (250-300g) were divided into following four groups such as: control, sham, stenosis and cyclodextrin-garcinol complex. Daily body weights were recorded. Cyclodextrin-garcinol complex (20 mg/kg/day) in distilled water, was administered orally to rats daily for 18 days and then the animals underwent surgery with aortic binding, the treatment was continued up to 4-6 weeks. Haemodynamic changes and electrocardiogram (ECG) were recorded in anaesthetized rats. Results: Pressure overload induced by arotic stenosis in rat resulted in significant myocardial hypertrophy and decreased endogenous antioxidants when compared with the control and sham group animals. Cyclodextrin-garcinol complex (20 mg/kg) showed significant cardioprotective activity by lowering the myocardial hypertrophy, level of lipid peroxidation (MDA content) as well as elevated the level of GSH. The results suggest pre-treatment of cyclodextrin-garcinol complex (20 mg/kg), may offer potential benefits in the management of cardiotoxicity and cardiac hypertrophy. Conclusion: It is concluded that cyclodextrin-garcinol complex (20 mg/kg) protected the haemodynamics of stenosized heart of rats by reduction of lipid peroxidation and preservation of endogenous antioxidants in rat heart

Effect of cyclodextrin garcinol complex on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats

Background: Garcinol is a polyisoprenylated benzophenone derivative present in the fruit rinds of Garcinia species namely Garcinia indica (common name 'Kokum') and Garcinia cambogia (common name 'Gombogee'). It appears to be involved in the regulation of oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions/ chemical agent. But garcinol is associated with severe limitation of instability and poor bioavailability which can be improved complexing cyclodextrin with garcinol (garcinol complex). Objective: The objective of the present study was to investigate effect of cyclodextrin with garcinol complex (20 mg/kg), on Iso induced cardiotoxicity and cardiac hypertrophy in rats.Methods: Male Wistar rats (250-300g) were divided into following 4 groups of six animals each. Group 1 was control (distilled water 2 ml/kg/day orally for 18 days and water for injection by i.p. from day 9 to day 18), group 2 was cyclodextrin (cyclodextrin 2 ml/kg/day orally for 18 days and water for injection by i.p. from day 9 to day 18), group 3 Iso (distilled water 2 ml/kg/day orally for 18 days and isoproterenol 1 mg/kg by i.p. from day 9 to day 18), group 4 garcinol complex (20 mg/kg/day orally for 18 days and isoproterenol 1 mg/kg by i.p. from day 9 to day 18). After 24 hrs of last dose of isoproterenol, electrocardiogram (ECG) and heart rate were recorded in anaesthetized rats. The animals were sacrificed by overdose of ether. The hearts of animals were isolated for measurement of reduced glutathione (GSH) and lipid peroxidation (MDA). Results: Isoproterenol treated rats showed significant myocardial hypertrophy, decreased endogenous antioxidants when compared with the control group animals. The garcinol complex (20 mg/kg) treatment for 18 days showed significant cardioprotective activity by lowering the myocardial hypertrophy, level of lipid peroxidation (MDA content) as well as elevated the level of GSH. The results suggest pre-treatment of garcinol complex (20 mg/kg), may offer potential benefits in the management of cardiotoxicity and cardiac hypertrophy. Conclusion: It is thus concluded that Garcinol Complex (20 mg/kg) administration offered significant protection against isoproterenol induced cardiotoxicity and cardiac hypertrophy as well as decreased myocardial injury by preservation of endogenous antioxidants and reduction of lipid peroxidation in rat heart

Formulation and Evaluation of Fixed Dose Combination Tablets of Antifungal Drugs for Candida albicans Resistant to Fluconazole

Background: The emergence of Candida albicans strains resistant to fluconazole (FLZ) had raised interest on combining other antifungals with FLZ. In vitro and clinical studies had indicated synergistic interaction between terbinafine and FLZ against strains resistant to FLZ and improved therapeutic efficacy. Objective: Formulation and evaluation of fixed dose combination (FDC) tablets of terbinafine HCl (TH) and FLZ for avoidance of resistance and improved therapeutic efficacy against C. albicans infections.  Method: The compatibility of TH and FLZ together and with excipients was determined by FTIR spectroscopy. A UV-visible spectroscopic Q-absorbance ratio method was developed and validated for linearity, accuracy, precision, LOD and LOQ for simultaneous estimation of TH and FLZ. The FDC tablets was prepared by wet granulation using hydroxy propyl cellulose (1%, 2%, 3%, 4% and 5%) as binder and evaluated for pre-compression and post-compression parameters. Result and Discussion: The TH and FLZ were compatible together and with excipients used in FDC. The linearity range was found to be 0.5-3.0 µg/ml and 80-400 µg/ml for TH and FLZ, respectively. Percent RSD was less than 2% indicating good accuracy and precision for proposed method. The hardness and disintegration time of tablets increased and friability decreased with increased binder concentration. Formulation F2 and F3 showed more than 80% drug release within 30 minutes. Conclusion: The TH and FLZ were compatible and can be formulated as a FDC tablet. The UV-Visible spectrophotometric method developed for simultaneous estimation was simple, accurate and sensitive. Keywords: Terbinafine, Fluconazole, Q-absorbance, Fixed Dose Combination, Candida albican