Effects and Mechanism of Rutin from Buckwheat Flowers and Leaves (RBFL) on Renal Injury of Diabetic GK Rats

LATIN AMERICAN JOURNAL OF PHARMACY(2019)

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Abstract
The objective was to investigate the protective effects of rutin from buckwheat flowers and leaves (RBFL) on the renal lesions in Goto-Kakizaki (GK) rats with spontaneous type 2 diabetes mellitus. Wistar rats from the same source were used as control group; the GK rats were randomly assigned to five groups: the control group; the Model group; the Low-RBFL treated group (L-RBFL, 100 mg/kg.day); the Middle-RBFL treated group (M-RBFL, 200 mg/kg.day); the High-RBFL treated group (H-RBFL, 400 mg/kg.day). The fasting blood glucose (FBG) was detected by blood glucosemeter; 24 h urinary protein excretion rate (24 UAER) were detected using automatic biochemical analyzer. The urine endogenous creatinine clearance rate (Ccr), blood and renal glycation endproducts (AGEs) were measured by automatic biochemical analyzer. Morphological changes of rats' renal tissue were determined via HE staining and Masson staining. kidney tissue. Ultrastructural changes were observed by electron microscopy. RBFL treatment could significantly improve kidney damage in GK rats. The expression levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (ifunp-9) in renal tissue were determined by Western-Blot. FBG was significantly reduced in the GK rats treated with RBFL. The RBFL significantly decreased 24 h UAER, and increased urinary Ccr in GK rats. Blood glucose, 24 UAER, SCr, and Ccr were significantly increased in each group of the model group, and the above indexes of RBFL were increased in a dose-dependent manner. The AGEs contents in serum and kidney tissues in the model group were significantly higher than those in the normal group (p < 0.01). RBFL had inhibitory effect on AGES in serum and kidney tissues, especially at high dose (p < 0.01). Compared with the control group, mmp-9 expression in kidney of model group and RBFL group significantly decreased (P < 0.05). Compared with the model group, RBFL increased in the high-dose group (P < 0.05). VEGF protein expression in renal tissue of rats in the diabetic group was significantly increased compared with that in the normal group (P < 0.01). Compared with the diabetic group, VEGF expression in renal tissue of rats in the RBFL high and medium dose groups was decreased (P < 0.01). Compared with the RBFL low-dose group, VEGF expression was further decreased in renal tissue of rats in the RBFL high-dose group (P < 0.05). RBFL have a protective effect on blood glucose in GK rats, and can reduce or delay T2DM kidney damage. The mechanism may be through reducing the formation of AGEs, and it may also be related to the reduction of VEGF and mmp-9 expression in renal tissue and the alleviation of renal tissue fibrosis.
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Key words
buckwheat flowers and leaves,kidney damage,rutin,type 2 diabetes mellitus
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