Prevention of Streptozotocin-induced Diabetic Nephropathy by the Lupane-type Triterpene Isolated From the Leaves of Acanthopanax Gracilistylus

Yang Yang*, Jiao Luo**, Man-Xia Lu**, Hong-Chi Zhang*, Zhi-Peng An*, Xiang-Qian Liu**,#, Eun-Hee Hwang***;#

*School of Life Sciences, Shanxi Datong University, Datong, China - **School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China - ***Department of food and Nutrition, Wonkwang University, Iksan, Korea

Acanthopanax gracilistylus is traditionally used to treat bone pains, arthritis, and rheumatism by the rook bark. To evaluate the renoprotective effect of the acankoreagenin, from the leaves of Acanthopanax gracilistylus (LAG), glucose loaded and streptozotocin (STZ) induced diabetic rats. The diabetic nephropathy (DN) rats were induced with STZ (70 mg/kg) by a single intraperitoneal injection. The acankoreagenin, was administered orally to normal and diabetic rats with guava extract and solvent control as comparison groups. Long term effects like kidney function, tumor necrosis factor-alpha (TNF-a) level, oxidative stress biomarkers, histopathology of kidney tissues were investigated. The results showed that acankoreagenin (2 mg/kg) treatment showed significant reduction in kidney function and TNF-a levels. The kidney tissue was used for immunohistochemical and histopathological measurement with transforming growth factor beta (TGF-β). Treatments with 2 mg/kg acankoreagenin group resulted renal oxidative stress (glutathione lever was increased from 0.36 to 1.53 uM/mg protein). Through inhibiting the TGF-β, the renal fibrosis was suppressed in STZ-induced diabetic rats. In renal tissues, histopathological injury was also observed. These findings are in support of the beneficial effect with the acankoreagenin treatment in antidiabetic and DN effects in streptozotocin induced diabetic rats.