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Shenqi Jiangtang Granule Ameliorates Kidney Function by Inhibiting Apoptosis in a Diabetic Rat Model.

ABSTRACT: Diabetic nephropathy (DN) is a major microvascular complication of diabetes. In addition to moderating hyperglycemia, Shenqi Jiangtang Granule (SJG) had a beneficial effect on kidney function in a clinical trial. However, the mechanism involved remains unclear. This study was conducted to identify the underlying molecular mechanisms. A diabetic rat model was generated by using a high-fat diet and streptozotocin (STZ) injection. Then, rats were given SJG at dosages of 400?mg/kg/d or 800?mg/kg/d by gavage for 8 weeks. After 8 weeks of treatment, blood glucose, serum creatinine, blood urea nitrogen (BUN), and 24-h urinary albumin were measured. Histochemical staining and TdT-mediated dUTP nick-end labeling (TUNEL) assays were performed in kidney. Kidney genomic expression in the SJG-treated group and diabetic group was detected by using a genome expression microarray. We found that SJG treatment reduced blood glucose, serum creatinine, BUN, and 24-h urinary albumin and affected kidney histology. The gene array revealed that the expression of 99 genes increased and the expression of 91 genes decreased in the HSJG group, compared with those of in the diabetic group. Pathway and gene ontology analysis of the differentially expressed genes showed an enrichment of the apoptosis pathway. SJG treatment reduced TUNEL- and caspase-3-positive cells in diabetic kidneys. SJG upregulated Bcl-2 and regucalcin expressions and reduced casp3 and Apaf1 expressions in diabetic rats. Our results suggest that SJG exerts a renal protective effect through the inhibition of cell apoptosis in a diabetic rodent model.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6886351 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Shenqi Jiangtang Granule Ameliorates Kidney Function by Inhibiting Apoptosis in a Diabetic Rat Model.

Zhang Qian Q Xiao Xinhua X Zheng Jia J Li Ming M Yu Miao M Ping Fan F Wang Tong T Wang Xiaojing X

Evidence-based complementary and alternative medicine : eCAM 20191120

Diabetic nephropathy (DN) is a major microvascular complication of diabetes. In addition to moderating hyperglycemia, Shenqi Jiangtang Granule (SJG) had a beneficial effect on kidney function in a clinical trial. However, the mechanism involved remains unclear. This study was conducted to identify the underlying molecular mechanisms. A diabetic rat model was generated by using a high-fat diet and streptozotocin (STZ) injection. Then, rats were given SJG at dosages of 400 mg/kg/d or 800 mg/kg/d b ...[more]

PMID: 31827549

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Project description:Diabetes mellitus (DM) is an independent risk factor for cognitive impairment. Although the etiology of diabetic cognitive impairment is complex and multifactorial, the hippocampus neuronal apoptosis is recognized as a main cause of diabetes-induced cognitive impairment. 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) was purified from the roots of Averrhoa carambola L. Previous research demonstrated that DMDD was safe and effective in delaying some diabetic complications. However, the efficacy of DMDD to ameliorate diabetic cognitive impairment in type 2 diabetes mice has not been reported. In the present study, the behavioral evaluation was performed by Y maze and novel object recognition in db/db mice. Gene expression profiles were detected using mouse lncRNA microarray analysis in the hippocampi of db/db mice. Changes in the neurodegeneration-associated proteins and the apoptosis-related proteins were determined in both db/db mice and high glucose-treated HT22 cells by Western blotting. We observed that DMDD treatment significantly ameliorated the spatial working memory and object recognition memory impairment in db/db mice. Further study showed that neurodegeneration-associated protein tau was decreased after DMDD treatment in the hippocampi of db/db mice. Eleven lncRNAs and four mRNAs including pro-apoptotic gene Hif3a were significantly differently expressed after DMDD treatment in the hippocampi of db/db mice. The expression of Hif3a, cleaved parp, and caspase 3 proteins was significantly increased in the hippocampi of diabetic db/db mice compared with db/m control mice and then decreased after DMDD treatment. Similar beneficial effects of DMDD were observed in HG-treated HT22 cells. These data indicate that DMDD can alleviate cognitive impairment by inhibiting neuronal apoptosis through decreasing the expression of pro-apoptotic protein Hif3a. In conclusion, our study suggests that DMDD has great potential to be a new preventive and therapeutic compound for diabetic cognitive impairment.

Dataset Information

Shenqi Jiangtang Granule Ameliorates Kidney Function by Inhibiting Apoptosis in a Diabetic Rat Model.

Publications

Shenqi Jiangtang Granule Ameliorates Kidney Function by Inhibiting Apoptosis in a Diabetic Rat Model.

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