Renal Effects of Plant-Derived Oleanolic Acid in Streptozotocin-Induced Diabetic Rats

Abstract

Previous studies from our laboratories indicate that the antidiabetic effects of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract in streptozotocin-induced diabetic rats may be attributed in part to mixtures of triterpenes, oleanolic acid (3ß-hydroxy-olea-12-en-28-oic acid, OA) and ursolic acid (3ß -hydroxyl-urs-12-en-28-oic acid, UA). For the bioactive compounds to have potential in diabetes management, they should alleviate or prevent complications of diabetes mellitus, kidney function, and cardiovascular disorders. This study was, therefore, designed to assess whether S. cordatum leaf derived OA influenced renal function evaluated by the ability to increase urinary Na + outputs parameters and creatinine clearance (Ccr) of streptozotocin (STZ)-induced diabetic rats. Extraction and fractionation of S. cordatum powdered leaf ethyl acetate-solubles (EAS) yielded mixtures of OA/UA and methyl maslinate/methyl corosolate. Recrystallization of OA/UA mixture using ethanol afforded OA, the structure of which was confirmed by NMR spectroscopy ( 1 H & 13 C). Acute effects of OA on kidney function and mean arterial blood pressure (MAP) were investigated in anesthetized rats challenged with hypotonic saline after a 3.5-h equilibration for 4h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. OA was added to the infusate during the treatment period. Chronic effects of OA were studied in individually caged rats treated twice daily with OA (60 mg/kg, p.o.) for five weeks. By comparison with respective control animals administration, OA significantly increased Na + excretion rates of non-diabetic and STZ-induced diabetic rats without affecting urine flow, K + and Cl − rates. At the end of five weeks, OA treatment significantly (p < 0.05) increased Ccr in non-diabetic (2.88 ± 0.14 vs. 3.71 ± 0.30 ml/min) and STZdiabetic rats (1.81 ± 0.32 vs. 3.07 ± 0.16 ml/min) with concomitant reduction of plasma creatinine concentration (n = 6 in all groups). OA also caused significant decreases in MAP in nondiabetic and STZ-induced diabetic rats. These findings suggest that OA may have beneficial effects on some processes associated with renal derangement of STZ-induced diabetic rats.

The Effects ofSyzygium aromaticum-Derived Oleanolic Acid on Kidney Function of Male Sprague–Dawley Rats and on Kidney and Liver Cell Lines

“…The solvents were removed under reduced pressure to give corresponding residues of hexane-solubles, dichloromethane-solubles, ethyl acetatesolubles (EAS), and methanol-solubles. Recrystallization of EAS which had been previously shown to contain OA ursolic acid/methyl maslinate/methyl corosolate 3,15 with ethanol yielded pure OA, whose structure was confirmed by spectroscopic analysis using 1D and 2D, 1 H and 13 C nuclear magnetic resonance techniques. Preliminary studies indicated that the S. aromaticum-isolated OA and commercial OA were similar and hence the plantextracted OA was used in the experiments as it costs less.…”

“…1,2 However, increasing evidence suggests that OA possesses hypoglycemic properties and may also have beneficial effects on some processes associated with impaired kidney function in diabetes. 3,4 Indeed, OA appears to reverse the previously reported inability of the kidney to excrete Na þ in streptozotocin (STZ)-induced diabetic rats. 5 These findings suggest that OA may be influencing transport processes in the proximal tubule, the site for the reabsorption of approximately two-thirds of the Na þ that enters the tubular fluid by glomerular filtration.…”

“…16 The rats were prepared for acute renal clearance studies and MAP using a modified procedure that has been previously described. 3 Briefly, the rats were anesthetized by intraperitoneal injection of inactin [5-ethyl-5-(1 0 -methylpropyl)-2-thiobarbiturate, 0.11 g kg À1 body weight] (Sigma Aldrich, St. Louis, MO, USA) and tracheotomy was performed. The right jugular vein was cannulated to allow a continuous intravenous infusion of saline.…”

“…3,4 Air-dried powdered flower buds of S. aromaticum were exhaustively extracted thrice at 24-h intervals sequentially with 3 L of hexane, dichloromethane, ethyl acetate, and methanol at room temperature. The solvents were removed under reduced pressure to give corresponding residues of hexane-solubles, dichloromethane-solubles, ethyl acetatesolubles (EAS), and methanol-solubles.…”

The Renal Effects of Blood Glucose-Lowering Plant-Derived Extracts in Diabetes Mellitus—an Overview

“…[71] Cornus officinalis + ↓ Kidney ROS [72] Gongronema latifolium + ↑ Superoxide dismutase (SOD), glutathione peroxidase [73] Rheum emodi − (GPx), reduced glutathione (GSH), catalase, etc. [74] Vigna angularis − Renoprotection [75] Helicrysium ceres + Amelioration of renal function [76] Oleanolic acid (Syzygium cordatum) + ↑ GFR [77] Sclerocarya birrea + ↓ Plasma urea and creatinine concentrations [19] Opunthia megacantha + ↓ Urinary protein concentration [20] Persea americana + [78] Jawarishi Zarooni Sada (a polyherbal unani formulation) − [79] Corni fructus + Maintenance of kidney structure [80] Curcumin (Curcumin longa) + ↓ Kidney levels of RAGE, AGE, TGF-ß 1 [81] Allium sativum and Zingiber officinale + ↓ Extra-cellular matrix proteins (e.g., fibronectin) [82] Momordica charantia + ↓ Renal hypertrophy [26] Coptis chinensis and Phellodendron amurense + [49] Hypoxis hemerocallidea + Reno-toxic effects [66] Opunthia megacantha + ↓GFR↑ serum urea and creatinine concentrations [83] …”