Resveratrol provides benefits in mice with type II diabetes‑induced chronic renal failure through AMPK signaling pathway

Objectives. This study investigates the effect of Qingshen Granules (QSG) on chronic renal failure patients and the HIF-1α/Wnt/β-catenin signaling pathway. Methods. Subjects were randomly divided into treatment and control groups, with 42 patients in each group. Participants in the treatment group received 10 g oral doses of QSG 3 times a day, for 12 weeks, whereas subjects in the control group were given a placebo. The effective rates of traditional Chinese medicine (TCM) symptom, serum creatinine (Scr), and estimate glomerular filtration rate (eGFR) as well as the serum levels of HIF-1α, Wnt1, β-catenin, α-SMA, and E-cadherin were evaluated. Results. Eighty patients completed the treatment program and two dropped out. After 12 weeks, the effective rates of TCM symptom and eGFR were found to be higher in the treatment group than in the control group, with statistically significant differences (P = 0.024 and 0.019, respectively). Meanwhile, lower levels of HIF-1α, Wnt1, β-catenin, α-SMA, and E-cadherin were detected in the treatment group, and the differences were statistically significant (P ≤ 0.001, P = 0.001, P ≤ 0.001, P ≤ 0.001, and P = 0.039). No adverse events occurred during the study. Conclusions. QSG can alleviate the clinical symptoms of chronic renal failure (CRF) and protect renal function in patients by influencing the HIF-1α/Wnt/β-catenin signaling pathway. The treatment exhibits no adverse effects and is thus safe to be used by humans.

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A Network Pharmacology-Based Approach to Investigating the Mechanisms of Fushen Granule Effects on Intestinal Barrier Injury in Chronic Renal Failure

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/2097569 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Miaoru Han ◽

Hangxing Yu ◽

Kang Yang ◽

Panying Liu ◽

Haifeng Yan ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Signaling Pathway ◽

Intestinal Barrier ◽

Enrichment Analysis ◽

Control Group ◽

T84 Cells ◽

Protein Expressions ◽

Group Protein ◽

Cox 2

Purpose. Fushen Granule (FSG) is a Chinese medicine prepared by doctors for treating patients with chronic renal failure, which is usually accompanied by gastrointestinal dysfunction. Here, we explore the protective effect of FSG on intestinal barrier injury in chronic renal failure through bioinformatic analysis and experimental verification. Methods. In this study, information on the components and targets of FSG related to CRF is collected to construct and visualize protein-protein interaction networks and drug-compound-target networks using network pharmacological methods. DAVID is used to conduct gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, it is validated by in vitro experiments. In this study, the human intestinal epithelial (T84) cells are used and divided into four groups: control group, model group, FSG low-dose group, and FSG high-dose group. After the experiment, the activity of T84 cells is detected by a MTT assay, and the expressions of tight junction protein ZO-1, claudin-1, nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) are examined by immunofluorescence and/or western blotting. Results. Eighty-six potential chronic renal failure-related targets are identified by FSG; among them, nine core genes are screened. Furthermore, GO enrichment analysis shows that the cancer-related signaling pathway, the PI3K-Akt signaling pathway, the HIF1 signaling pathway, and the TNF signaling pathway may play key roles in the treatment of CRF by FSG. The MTT method showed that FSG is not cytotoxic to uremic toxin-induced injured T84 cells. The results of immunofluorescence and WB indicate that compared with the control group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is decreased and protein expressions level of HO-1, MDA, and COX-2 is increased after urinary toxin treatment. Instead, compared with the model group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is increased and protein expressions level of HO-1, MDA, and COX-2 is decreased after FSG treatment. Conclusion. FSG had a protective effect on urinary toxin-induced intestinal epithelial barrier injury in chronic renal failure, and its mechanism may be related to the upregulation of Nrf2/HO-1 signal transduction and the inhibition of tissue oxidative stress and inflammatory responses. Screening CRF targets and identifying the corresponding FSG components by network pharmacological methods is a practical strategy to explain the mechanism of FSG in improving gastrointestinal dysfunction in CRF.

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