Document Type

Article

Publication Date

10-12-2018

Journal Title or Book Title

Archives of Natural and Medicinal Chemistry

Volume

Volume 2018

Issue

2

Version

Publisher's PDF

Publisher's Statement

Creative Commons Attribution-ShareAlike 4.0 International License. With this license readers can share, distribute, download, even commercially, as long as the original source is properly cited. Amin RP, Patel SN, Kumar S, Zito WS, Barletta MA (2018) Effects of Usnic Acid on Hyperglycemia and Renal Function in Streptozotocin-Induced Diabetic Rats. Arch Nat Med Chem ANMC-119. DOI: 10.29011/ANMC-119. 000019

DOI

10.29011/ANMC-119. 000019

Abstract

Background: Diabetic hyperglycemia and glomerular hyper filtration play a causative role in the progression of chronic kidney disease. Renal glucose handling via Sodium-Glucose Cotransporter (SGLT)-2 is a targetable approach and SGLT-2 inhibitors have proven therapeutic benefits in diabetic kidney disease. Usnic Acid (UA) is an active constituent of lichen species and symbiotic organism of algae and fungi, which is variously studied in folk medicine. The objective of this study was to demonstrate the beneficial effects of UA on glucose homeostasis and renal function in streptozotocin-induced diabetic Sprague-Dawley rats and to determine whether UA has an effect on regulation of SGLT that may further aid in glucoregulation and renal function. Methods: Type 1 diabetes was induced in Sprague-Dawley rats with Streptozotocin (STZ, 60mg/kg) by intraperitoneal route on day 0. Diabetic rats were treated with UA (75 mg/kg) from day 15 to 35 via oral gavage. On day 35, urine was collected and Oral Glucose Tolerance Test (OGTT) was performed. After OGTT, blood was collected through cardiac puncture and kidneys were preserved for biochemical analysis. The results are expressed as mean ± standard error of the mean for n=8 rats per study group. The data were subjected to 1-way or 2-way ANOVA with Bonferroni’s multiple comparison post hoc test using Graph Pad Prism 5 and were considered significant at p≤0.05. Results: Diabetic rats chronically treated with UA had improved hyperphagia, hyperglycemia and glucose intolerance, glomerular hyper filtration, and urinary protein excretion (p<0.05). However, UA did not prevent loss of circulating insulin in diabetic rats. UA’s blood glucose lowering effect was associated with enhanced diuretic-glucosuric response and decreased protein expression of renal SGLT-1 (p<0.05). While protein expression of SGLT-2 was partially increased in the diabetic kidney and it was not decreased by UA. Metabolic corrections with UA treatment occurred in parallel with reductions in uremia and improvement of renal function indices. Additionally, in diabetic rat kidney, UA treatment corrected oxidative changes. Conclusions: Based on preliminary findings we conclude that chronic treatment of UA may act in an insulin-independent manner in lowering of diabetic hyperglycemia and improvement of renal function.

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Creative Commons Attribution-Share Alike 4.0 License
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