The Qi-Bang-Yi-Shen formula ameliorates renal dysfunction and fibrosis in rats with diabetic kidney disease &lt;em&gt;via&lt;/em&gt; regulating PI3K/AKT, ERK and PPARγ signaling pathways

Wang, Zhi; Chen, Teng; Li, Junhui; Wang, Niansong

doi:10.4081/ejh.2023.3648

Cited by 3 publications

(2 citation statements)

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“…PS plays a role in cellular injury, specifically targeting podocyte integrity and function [ 40 ]. In vivo experiments demonstrated that the DKD mice exhibited elevated levels of CRE, BUN, urine protein, and endotoxin, which are important indicators for evaluating kidney function [ 41 , 42 ]. After treating the mice with HJXJ, their behavior and symptoms saw a significant improvement overall, which is consistent with previous studies [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Huajuxiaoji Formula Alleviates Phenyl Sulfate‐Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis

Zhang,

Bi,

Zhou

et al. 2024

Journal of Diabetes Research

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Background: One of the most common microvascular complications of diabetes is diabetic kidney disease (DKD). The Huajuxiaoji formula (HJXJ) has shown clinical efficacy for DKD; however, its regulatory mechanisms against DKD remain elusive. We investigated NLRP3 inflammasome and the mechanisms of HJXJ by which HJXJ alleviates DKD.Methods: Phenyl sulfate (PS) was used to establish DKD models. HJXJ was administered to mice through intragastric or made into a pharmaceutical serum for the cell cultures. Biological indicator levels in mouse blood and urine were analyzed, and kidney tissues were used for HE, Masson, and PAS staining. ELISA and western blotting were used to detect inflammatory cytokines and protein levels, respectively. Reactive oxygen species (ROS) production and pyroptosis were evaluated using flow cytometry. Lentiviral vector‐mediated overexpression of NLRP3 was performed to determine whether NLRP3 participates in the antipyroptotic effect of HJXJ.Results: HJXJ significantly reduced the severity of the injury and, in a dose‐dependent manner, decreased the levels of biological markers including creatinine, blood urea nitrogen, urine protein, and endotoxin, as well as inflammatory cytokines such as interleukin (IL)‐1β, IL‐18, tumor necrosis factor‐α, and IL‐6 in DKD mice. Treatment with HJXJ reversed the downregulation of podocin, nephrin, ZO‐1, and occludin and upregulated ROS, NLRP3, Caspase‐1 P20, and GSDMD‐N induced by PS. Moreover, the upregulation of NLRP3 expression increased the number of cells positive for pyroptosis. HJXJ suppressed pyroptosis and inflammasome activation by inhibiting NLRP3 expression.Conclusions: Generally, HJXJ has the potential to reduce DKD injury and exerts anti‐DKD effects by inhibiting the NLRP3‐mediated NLRP3 inflammasome activation and pyroptosis in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Huajuxiaoji Formula Alleviates Phenyl Sulfate‐Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis

Zhang,

Bi,

Zhou

et al. 2024

Journal of Diabetes Research

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“…Creatinine (CRE), blood urea nitrogen (BUN), and uric acid (UA) serve as crucial indicators for assessing renal function, effectively reflecting the renal and glomerular filtration functions of the body. Deviations from normal values of these indicators indicate impaired renal function [24]. Superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) primarily serve as indicators of the body's antioxidant stress level.…”

Section: Discussionmentioning

confidence: 99%

Study of the Mechanism of Astragali Radix in Treating Type 2 Diabetes Mellitus and Its Renal Protection Based on Enzyme Activity, Network Pharmacology, and Experimental Verification

Li,

Zhang,

Liu

et al. 2023

Molecules

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Astragali Radix (AR) is a common Chinese medicine and food. This article aims to reveal the active role of AR in treating Type 2 diabetes mellitus (T2DM) and its renal protective mechanism. The hypoglycemic active fraction was screened by α-glucosidase and identified by UPLC-QE-Orbitrap-MS spectrometry. The targets and KEGG pathway were determined through the application of network pharmacology methodology. Molecular docking and molecular dynamics simulation technology were used for virtual verification. Subsequently, a mouse model of T2DM was established, and the blood glucose and renal function indexes of the mice after administration were analyzed to further prove the pharmacodynamic effect and mechanism of AR in the treatment of T2DM. HA was determined as the best hypoglycemic active fraction by the α-glucosidase method, with a total of 23 compounds identified. The main active components, such as calycoside-7-O-β-D-glucoside, methylnisoline, and formononetin, were revealed by network pharmacology. In addition, the core targets and the pathway have also been determined. Molecular docking and molecular dynamics simulation techniques have verified that components and targets can be well combined. In vivo studies have shown that AR can reduce blood sugar levels in model mice, enhance the anti-inflammatory and antioxidant activities of kidney tissue, and alleviate kidney damage in mice. And it also has regulatory effects on proteins such as RAGE, PI3K, and AKT. AR has a good therapeutic effect on T2DM and can repair disease-induced renal injury by regulating the RAGE/PI3K/Akt signaling pathway. This study provides ideas for the development of new drugs or dietary interventions for the treatment of T2DM.

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POU2F2 activates the Akt/mTOR signalling pathway and enhances B lymphocyte function during diabetic kidney disease by promoting PIK3CD transcription

Li,

Cao,

et al. 2024

Nephrology

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BackgroundPhosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit delta (PIK3CD) is the predominant isoform of the catalytic subunit of PI3K in lymphocytes. Based on comprehensive bioinformatics, this study explores the functions of PIK3CD in diabetic kidney disease (DKD) progression in mice and B lymphocyte activity.MethodsNon‐obese diabetic (NOD) mice that spontaneously develop DKD were applied as animal models. Lentiviral vector‐mediated PIK3CD silencing was introduced in mice, followed by histological staining and biomarker assessments to evaluate DKD‐associated symptoms. The activity of the Akt/mTOR signalling pathway was determined by western blot analysis. Following bioinformatics analyses, the interaction between POU class 2 homeobox 2 (POU2F2) and PIK3CD in B lymphocytes was determined by chromatin immunoprecipitation and luciferase reporter assays. Their functions in B cell function were identified by MTT, flow cytometry and IgG deposition assessment.ResultsPIK3CD was found to be highly expressed in the kidney of DKD mice. Knockdown of PIK3CD inactivated the Akt/mTOR signalling, thus ameliorating tissue injury and fibrosis, enhancing the expression of AQP1 and decreasing urinary NGAL contents, UACR, BUN and β‐NAG/creatinine ratio. These effects were negated by the Akt‐specific activator SC79. POU2F2 was found to promote PIK3CD transcription by binding to its promoter, thus activating the Akt/mTOR pathway. Knockdown of POU2F2 suppressed B cell proliferation in vitro and decreased B cell population and IgG deposition in the mouse kidney. However, these trends were reversed upon additional PIK3CD overexpression.ConclusionThis study demonstrates that POU2F2 mediates PIK3CD‐dependent Akt/mTOR signalling activation, thus enhancing B lymphocyte function and promoting DKD progression.image

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The Qi-Bang-Yi-Shen formula ameliorates renal dysfunction and fibrosis in rats with diabetic kidney disease <em>via</em> regulating PI3K/AKT, ERK and PPARγ signaling pathways

Cited by 3 publications

References 59 publications

Huajuxiaoji Formula Alleviates Phenyl Sulfate‐Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis

Huajuxiaoji Formula Alleviates Phenyl Sulfate‐Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis

Study of the Mechanism of Astragali Radix in Treating Type 2 Diabetes Mellitus and Its Renal Protection Based on Enzyme Activity, Network Pharmacology, and Experimental Verification

POU2F2 activates the Akt/mTOR signalling pathway and enhances B lymphocyte function during diabetic kidney disease by promoting PIK3CD transcription

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