Pharmacological safety of dimethoxy curcumin-human serum albumin conjugate for potential therapeutic purpose.

Medicinal properties of curcumin are widely published. Previously, researchers used curcuminoid mixture comprising three chemical forms, out of which, the highest quantity is the most active molecule-dimethoxy curcumin (DMC). Reduced bioavailability, poor aqueous solubility, and quick hydrolytic degradation of DMC have projected challenges limiting its therapeutic value. However, selective conjugation of DMC with human serum albumin (HSA) enhances drug stability and solubility by several folds. Studies using animal models demonstrated potential anti-cancer/anti-inflammatory effects of DMCHSA; both studies showed results of local administration in peritoneal cavity and rabbit knee joint. DMC has prospects as intravenous therapeutic agent because carrier is HSA. However, before in vivo testing, important preclinical data required are toxicological safety and bioavailability of soluble forms of DMC. This study evaluated absorption, distribution, metabolism, and excretion of DMCHSA. Imaging technology and molecular analysis proved bio-distribution. The study also assessed the pharmacological safety of DMCHSA in mice in terms of its acute and sub-acute toxicity, complying with regulatory toxicology. Overall, the study demonstrated the safety pharmacology of DMCHSA upon intravenous infusion. This is a novel study establishing the safety of highly soluble and stable formulation of DMCHSA, qualifying it for intravenous administration and further efficacy evaluation in suitable disease models.

Pharmacokinetics and Pharmacodynamics of Avian Egg-Yolk Derived Pure Anti-Snake Venom in Healthy and Disease Animal-Model.

The absence of Fc receptor binding, cost-effective production potential in large quantities in pure form, and better storage stability of avian immunoglobulin (IgY) advocate its therapeutic use as anti-snake venom (ASV). This study develops pure anti-neurotoxin (ANT- IgY) by immunizing White Leghorn hens with Cobra and Krait venoms for demonstrating antigen-antibody binding in vitro/in vivo. The purified IgY from immunized egg-yolk showed immunoprecipitation in Ouchterlony's Double Diffusion (ODD) experiment. For characterizing ANT-IgY distribution and clearance pattern, the study utilized an enzyme-linked immunosorbent assay (ELISA) in serum at different intervals following intravenous (IV) administration. The Kinetica 5.1 software estimated pharmacokinetic parameters, including half-life. The IgY showed a time-dependent elimination through the intestinal route in fecal matter. After conjugating with a fluorochrome-Vivotag-750S, injected the purified ANT-IgY intravenously into the healthy mice. Subsequently, captured live-animal images to demonstrate the distribution and elimination profile of the molecule. Intramuscular injection of fluorochrome-tagged venom created the envenomed mice model. The live-animal images demonstrated the quick mobilization of venom into vital tissues. Intravenous administration of tagged ANT-IgY in the envenomed model showed the movement of ASV to the tissues venom traffics. The observed pharmacological benefit promise scope of ASV-IgY for therapeutic use.

Evaluation of diuretic efficacy and antiurolithiatic potential of ethanolic leaf extract of Annona squamosa Linn. in experimental animal models.

OBJECTIVE: The study is to investigate the diuretic and antiurolithiatic activities of ethanolic leaf extract of Annona squamosa Linn. in experimental animals. MATERIALS AND METHODS: For both studies, Wistar albino rats and two doses of extract (250 and 500 mg/kg) were used. Diuretic activity was evaluated by Lipschitz model. Urine volume and urine pH were noted, the concentration of sodium and potassium was estimated by flame photometry, and diuretic index, natriuretic index, and Lipschitz values were calculated from the results. Furosemide was used as a positive control. Ethylene glycol-induced urolithiasis model was used for antiurolithiatic study. Urine volume, urine pH, body weight, and biochemical parameters such as calcium, urea, uric acid, and creatine both from serum and urine were estimated. Antioxidant parameters and histopathological analysis of the kidney were evaluated. Cystone was used as a positive control in this study. Results were expressed as mean ± standard error of mean. Statistical analysis was carried out using one-way analysis of variance, followed by Dunnett's multiple comparison tests. RESULTS: In both diuretic and antiurolithiatic studies, both doses of the extract showed efficacy, and the dose of 500 mg/kg has shown a significant effect compared to positive control and negative control. CONCLUSION: The dose of 500 mg/kg showed a promising diuretic and antiurolithiatic activity.