Abstract
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.
Highlights
Diabetes mellitus (DM), a metabolic disorder characterized by hyperglycemia induced by insulin secretion deficiency and/or resistance to its action, affects more than millions of people across the world [1]
To further elucidate the relationship between target proteins and pathways, we identified 20 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways significantly associated with the target proteins (Table 9), and they were found to be involved in secretion, metabolism, and cellular signaling
From the Protein-Protein Interaction (PPI) of targeted proteins, we identified hub nodes which are markedly associated with diabetes
Summary
Diabetes mellitus (DM), a metabolic disorder characterized by hyperglycemia induced by insulin secretion deficiency and/or resistance to its action, affects more than millions of people across the world [1]. The above-mentioned side effects suggest that further development of new, safer, and more powerful oral antihyperglycemic agents, in long-term therapy, is needed. In this context, medicinal plants have emerged as promising adjuvants to treat chronic, oxidative stressmediated disorders [3]. Several medicinal plants recommended for the treatment of DM have been shown to protect β-cells, increase insulin secretion and glucose absorption by the adipose tissue, and decrease glucose absorption in the intestines [2, 4]. Treatments which involve the use of medicinal plants provoking antioxidative actions are highly recommended [6, 7]
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