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Protective effect of Huang Gan formula in 5/6 nephrectomized rats by depressing the Wnt/β-catenin signaling pathway.

ABSTRACT: Huang Gan formula (HGF) is a new traditional Chinese herbal medicine created according to the basic theory of traditional Chinese medicine. The aim of this study is to evaluate the effects of HGF on chronic kidney disease and determine the mechanisms of action. The extract of HGF was prepared, and qualitative and quantitative determination of phytochemical was performed with quadrupole time-of-flight mass spectrometer and high-performance liquid chromatography. Sprague-Dawley rats (n=72) were submitted to 5/6 nephrectomy (Nx), and then respectively treated with uremic clearance granule, losartan, HGF low dose, HGF middle dose, and HGF high dose once per day for 12 weeks. The sham group of operated rats (n=22) was treated with normal saline or HGF middle dose as a background control group. Blood and urine biochemical parameters, renal tissue morphology, and mRNA and proteins of Wnt/β-catenin signaling pathways were investigated. The results showed that the quality of the extraction process could be controlled, and a total of eight major compounds were identified and quantified. HGF could decrease the level of serum creatinine, blood urea nitrogen, and urine protein and increase the renal index and creatinine clearance rate in a dose-dependent manner. HGF also remarkably reduced the glomerulosclerosis and tubulointerstitial fibrosis by blocking the Wnt/β-catenin signaling pathway through inhibiting the Wnt1, β-catenin, transcription factor 4, and fibronectin 1 expressions, simultaneously measured through mRNA and protein levels in the remnant kidney. These results suggest that extraction of HGF could improve remnant renal function and possibly ameliorate glomerulosclerosis and tubulointerstitial fibrosis by depressing the Wnt/β-catenin signaling pathway.

SUBMITTER: Mo L

PROVIDER: S-EPMC4461094 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid β- (Aβ-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/β-catenin pathway.MethodsHealthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/β-catenin pathway-related proteins, respectively.ResultsOn the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of Aβ-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU+, Dcx+, BrdU+/Neun+, BrdU+/Dcx+ cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1+ and Iba1+/BrdU+ cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/β-catenin pathway by upregulating Wnt3a, β-catenin, Disheveled (Dvl), and p-GSK3β and downregulating p-β-catenin and GSK3β.ConclusionLME attenuates cognitive impairment in Aβ-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/β-catenin pathway.

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Protective effect of Huang Gan formula in 5/6 nephrectomized rats by depressing the Wnt/β-catenin signaling pathway.

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