Triterpene derivative improves the renal function of streptozotocin-induced diabetic rats: a follow-up study on maslinic acid

Abstract

Introduction: Reports indicate that oral administration of plant-derived maslinic acid (MA) exhibits hypoglycemic and renoprotective effects in streptozotocin (STZ)-induced diabetic rats. Challenges with triterpenes such as MA include low bioavailabilty which affects treatment efficacy in experimental animals. The goal of this study was to synthesize the MA derivative phenylhydrazine (PH-MA) in an effort to improve the efficacy of MA. Methods: Separate groups of non-diabetic and STZ-induced diabetic rats (n ¼ 6) were anesthetized and the jugular vein cannulated for the infusion of 0.077 M NaCl at 9 mL/h. The bladder was catheterized for collection the urine samples every 30 min. After 30.5 h equilibration period, consecutive 30 min urine collections were made over the subsequent 4 h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. PH-MA (22 mg/h) and MA (90 mg/h) were added during the treatment periods for analysis of proximal tubular Na þ handling, plasma aldosterone and arginine vasopressin in male Sprague-Dawley rats. Results: Intravenous infusion of PH-MA (22 mg/h) and MA (90 mg/h) significantly (p ˂ .05) increased Na þ output, fractional excretion of Na þ (FENa) and lithium (FELi). Interestingly, like MA, PH-MA significantly (p ˂ .05) increased glomerular filtration rate (GFR) over the treatment period and decreased plasma aldosterone levels. Our findings indicate that PH-MA inhibited sodium reabsorption in the proximal and distal tubule as shown by increased FENa and low plasma aldosterone levels, respectively. Conclusions: PH-MA is, therefore, a promising multitarget antidiabetic agent that may ameliorate kidney function of diabetic patients at a dose four times lower than the parent compound (MA).

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

“…Extensive research has demonstrated that natural oleanane-type pentacyclic triterpenes display potent inhibitory activity and selectivity against PTP1B [ 17 , 18 , 19 , 20 , 21 ]. Maslinic acid [ 22 , 23 ], oleanolic acid [ 24 , 25 , 26 ] and celastrol [ 27 , 28 , 29 ] are the most representative examples of this type of inhibitors. Less known is glycyrrhetinic acid (GA), which is an oleanane-type triterpene found abundantly (up to 24%) as glycyrrhizin in the root of licorice ( Glycyrrhiza glabra L.) [ 30 , 31 , 32 ].…”

Leishmanicidal Activity and Ultrastructural Changes of Maslinic Acid Isolated from Hyptidendron canum

“…In contrast, maslinic acid is present in different edible vegetables, commonly used in the human diet; thus it does not seem toxic for humans [20,22,34]. Furthermore, it was demonstrated that daily oral doses of maslinic acid did not alter the body weight, biochemical, or hematological parameters of experimental animals [35], and in diabetic rats this triterpene exhibited hepatic and renal protective properties [36,37], suggesting that this triterpene is safe to be used in different medical conditions, including leishmaniasis. ) infantum were treated with EC 50 s of maslinic acid, miltefosine, and amphotericin for 24 h; then cell membrane integrity A and mitochondrial membrane potential were analyzed using the probes Sytox green and rhodamine 123, respectively.…”

Phytotherapeutics Attenuation of Oxidative Stress, Inflammation and Lipid Peroxidation in Severe and Chronic Diseases

“…Moreover, plasma protein carbonyls have been shown to be a predictive biomarker of oxidative stress in chronic kidney disease, dialysis, and transplantation [56]. However, Mkhwanazi et al have reported that a maslinic acid triterpene derivative improved the renal function of streptozotocin-induced diabetic rats [37]. Furthermore, Mavondo et al chronologies how malarial inflammation-driven pathophysiology and were reduced by triterpene application in various in vivo and ex vivo experiments of Asiatic acid [34].…”