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Interdiscip Toxicol
2018 Dec 01;114:275-288. doi: 10.2478/intox-2018-0027.
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Novel pentacyclic triterpene isolated from seeds of Euryale Ferox Salisb. ameliorates diabetes in streptozotocin induced diabetic rats.
Ahmed D
,
Khan MI
,
Sharma M
,
Khan MF
.
Abstract
The present research was carried out to study the effect of 2β-hydroxybetulinic acid 3β-oleiate (HBAO), a novel compound isolated from the seeds of Euryale ferox salisb. on glycemic control, antioxidant status and histopathological morphological alterations in the liver, pancreas, kidney and heart in streptozotocin induced type-2 diabetes in rats. HBAO was isolated from the seeds of Euryale ferox salisb. according to Lee. Isolation of the active principle HBAO was performed for the first time. To date there are no reports on the isolation and evaluation of 2β-hydroxybetulinic acid 3β-oleiate (HBAO) from Euryale ferox salisb. Assessment of different biochemical parameters like the effect of HBAO on glycemic control, plasma insulin, glycosylated hemoglobin, hepatic glucose-6-phosphate dehydrogenase, glucose-6-phosphatase and fructose-1-6-biphosphatase, hepatic hexokinase, lipid profile, antioxidant marker and histopathology of pancreas, liver and kidney examination was done at the end of the experimentation, i.e. on day 45. HBAO exhibited remarkable improvement in glycemic control, lipid levels, plasma insulin, glycogenic liver enzymes and antioxidant activity in diabetic rats, along with progressive enhancement of distortive histopathological morphology of liver, pancreas and kidney. The results strongly suggest that HBAO could be a potential therapeutic agent in diabetes.
Figure 1. Chemical structure of isolated compound (HBAO).
Figure 2. Effect of HBAO on Blood Glucose at different time interval of therapy: Group 1: Normal control; Group 2: Normal + HBAO (60 mg/kg p.o.); Group 3: Diabetic Control (Infused with STZ 60 mg/kg i.p); Group 4: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; Group5: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; Group6: Diabetic + HBAO (60 mg/kg p.o ) & continue till End; Group 7: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
Figure 3. Effect of HBAO on Plasma Insulin at different time interval of therapy: Group 1: Normal control; Group 2: Normal + HBAO (60 mg/kg p.o.); Group 3: Diabetic Control (Infused with STZ 60 mg/kg i.p); Group 4: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; Group5: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; Group6: Diabetic + HBAO (60 mg/kg p.o ) & continue till End; Group 7: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
Figure 4. Effect of HBAO on Gluconeogenic hepatic enzymes at different time interval of therapy: Group 1: Normal control; Group 2: Normal + HBAO (60 mg/kg p.o.); Group 3: Diabetic Control (Infused with STZ 60 mg/kg i.p); Group 4: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; Group5: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; Group6: Diabetic + HBAO (60 mg/kg p.o ) & continue till End; Group 7: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
Figure 5. Effect of HBAO on Lipid Profile at different time interval of therapy: Group 1: Normal control; Group 2: Normal + HBAO (60 mg/kg p.o.); Group 3: Diabetic Control (Infused with STZ 60 mg/kg i.p); Group 4: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; Group5: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; Group6: Diabetic + HBAO (60 mg/kg p.o ) & continue till End; Group 7: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
Figure 6. Effect of HBAO on Antioxidant marker enzymes at different time interval of therapy: Group 1: Normal control; Group 2: Normal + HBAO (60 mg/kg p.o.); Group 3: Diabetic Control (Infused with STZ 60 mg/kg i.p); Group 4: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; Group5: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; Group6: Diabetic + HBAO (60 mg/kg p.o ) & continue till End; Group 7: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
Figure 7. Effect of HBAO on Body Weight at different time interval of therapy: Group 1: Normal control; Group 2: Normal + HBAO (60 mg/kg p.o.); Group 3: Diabetic Control (Infused with STZ 60 mg/kg i.p); Group 4: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; Group5: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; Group6: Diabetic + HBAO (60 mg/kg p.o ) & continue till End; Group 7: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
Figure 8. Effect of isolate HBAO on histological profile of Pancreas in normal, STZ-induced diabetic untreated and STZ-induced diabetic treated wistar rats. (Original magnification 40x, DXIT 1200 , Nikon, Japan). NPAN: Normal Control; PHBAO-60.: Normal + HBAO (60 mg/kg p.o.); STZP: Diabetic Control (Infused with STZ 60 mg/kg i.p); SPHBAO-20: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; SPHBAO-40-: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; SPHBAO-60: Diabetic + HBAO (60 mg/kg p.o.) & continue till End; PGLIM: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
Figure 9. Effect of isolate HBAO on histological profile of Kidney in normal, STZ-induced diabetic untreated and STZ-induced diabetic treated wistar rats. (Original magnification 40x, DXIT 1200 , Nikon, Japan). NKAN: Normal Control; KHBAO-60.: Normal + HBAO (60 mg/kg p.o.); STZK: Diabetic Control (Infused with STZ 60 mg/kg i.p); SKHBAO-20: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; SKHBAO-40-: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; SKHBAO-60: Diabetic + HBAO (60 mg/kg p.o.) & continue till End; KGLIM: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
Figure 10. Effect of isolate HBAO on histological profile of Liver in normal, STZ-induced diabetic untreated and STZ-induced diabetic treated wistar rats. (Original magnification 40x, DXIT 1200 , Nikon, Japan). NLAN: Normal Control; LHBAO-60.: Normal + HBAO (60 mg/kg p.o.); STZL: Diabetic Control (Infused with STZ 60 mg/kg i.p); SLHBAO-20: Diabetic + HBAO (20 mg/kg p.o.) & continue till End; SLHBAO-40-: Diabetic + HBAO (40 mg/kg p.o.) & continue till End; SLHBAO-60: Diabetic + HBAO (60 mg/kg p.o.) & continue till End; LGLIM: Diabetic + Glimepiride (10mg/kg p.o.) & continue till End. END = 45 Days.
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