The purpose of this study was to look into the effects of green coconut mesocarp juice extract (CMJE) on diabetes-related problems in streptozotocin- (STZ-) induced type 2 diabetes, as well as the antioxidative functions of its natural compounds in regulating the associated genes and biochemical markers. CMJE’s antioxidative properties were evaluated by the standard antioxidant assays of 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide radical, nitric oxide, and ferrous ions along with the total phenolic and flavonoids content. The α-amylase inhibitory effect was measured by an established method. The antidiabetic effect of CMJE was assayed by fructose-fed STZ-induced diabetic models in albino rats. The obtained results were verified by bioinformatics-based network pharmacological tools: STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba bioinformatics tools. The results showed that GC-MS-characterized compounds from CMJE displayed a very promising antioxidative potential. In an animal model study, CMJE significantly (
P
<
0.05
) decreased blood glucose, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, uric acid, and lipid levels and increased glucose tolerance as well as glucose homeostasis (HOMA-IR and HOMA-b scores). The animal’s body weights and relative organ weights were found to be partially restored. Tissue architectures of the pancreas and the kidney were remarkably improved by low doses of CMJE. Compound-protein interactions showed that thymine, catechol, and 5-hydroxymethylfurfural of CMJE interacted with 84 target proteins. Of the top 15 proteins found by Cytoscape 3.6.1, 8, CAT and OGG1 (downregulated) and CASP3, COMT, CYP1B1, DPYD, NQO1, and PTGS1 (upregulated), were dysregulated in diabetes-related kidney disease. The data demonstrate the highly prospective use of CMJE in the regulation of tubulointerstitial tissues of patients with diabetic nephropathy.
Controlled release formulation of recombinant human growth hormone (r-hGH) was achieved using poly lactide-co-glycolide (PLGA) polymer. Denaturation of r-hGH by dichloromethane during primary emulsification step of particle preparation was minimized by using human serum albumin whereas inclusion of sucrose and sodium bicarbonate helped in reducing protein denaturation during lyophilization and polymer particle degradation. Encapsulation efficiency of r-hGH entrapped in PLGA particles (size approximately 30 microm) was around 45% with protein load 20 microg of r-hGH/mg of polymer particles. Porous particles showed quick release of r-hGH in comparison to non-porous particles in vitro. More than 10 ng/mL of bioactive r-hGH was found in the serum of the experimental animals observed for a 30-day period after a single intramuscular injection of the polymeric formulation. Incorporation of optimal stabilizers is thus essential for the development of a stable, month long controlled release of polymer particle based r-hGH formulation.
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