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1.
J Pharmacol Sci ; 148(2): 204-213, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35063135

RESUMO

Epithelial mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs) dominates the pathology of diabetic nephropathy (DN). microRNAs (miRNAs) can influence the fate of DN via regulation of EMT. This study aimed to analyze the role of Icariin (ICA) in EMT of RTECs, hoping to provide theoretical basis for DN management. The DN rat model was established using streptozocin, followed by ICA treatment, histopathological observation, and detection of creatinine and blood urea nitrogen. In vitro cell models were established using high glucose (HG), followed by assessment of cell proliferation, apoptosis, and migration, and E-cadherin, α-SMA, miR-122-5p, and FOXP2 expressions. Cells were transfected with miR-122-5p mimics or si-FOXP2 for joint experiments with ICA. The targeting relationship between miR-122-5p and FOXP2 was verified. ICA repaired renal dysfunctions and glomerular structure abnormities of DN rats in a dose-dependent manner. In vitro, ICA improved proliferation while suppressed migration, apoptosis, and EMT of RTECs. miR-122-5p was up-regulated in DN rats and suppressed by ICA, and miR-122-5p targeted FOXP2. miR-122-5p up-regulation or FOXP2 down-regulation reversed the protective effects of ICA on HG-induced RTECs. Overall, our finding ascertained that ICA inhibited miR-122-5p to promote FOXP2 transcription, thereby attenuating EMT of RTECs and renal injury in DN rats.


Assuntos
Nefropatias Diabéticas/genética , Nefropatias Diabéticas/fisiopatologia , Células Epiteliais/fisiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Flavonoides/farmacologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Túbulos Renais/citologia , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Masculino , Ratos Sprague-Dawley , Transcrição Gênica/efeitos dos fármacos
2.
Front Chem ; 10: 1036380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438869

RESUMO

Type 2 diabetes mellitus (T2DM) is a chronic disease associated with many severe complications such as blindness, amputation, renal failure, and cardiovascular disease. Currently, the prevention and treatment of T2DM is a major global challenge as the number of aging and obese people is increasing. Traditional Chinese medicine offers the advantages of multi-target holistic and individual treatment for obesity and type 2 diabetes. However, most of the TCMs for T2DM are not scientifically evaluated. Here, Buyang Huanwu decoction (BYHWD), a widely used TCM formula, was used to explore scientific pharmacological activity against T2DM in rat models. First, BYHWD exhibited excellent inhibitory actions against body fat accumulation and increased blood triglyceride levels, and a high-fat diet (HFD) induced blood glucose elevation in diabetic rats. Moreover, 16S rDNA sequencing of fecal samples identified the distinct changes in the community composition of gut flora following BYHWD treatment, displayed as significantly increased Bacteroidetes and dramatically decreased Firmicutes at the phyla level, and the remarkable increase in the abundance of Lactobacillus and Blautia. Additionally, lipid metabolomics based on liquid chromatography-mass spectrometry revealed a significant shift of lipid metabolites in the liver after BYHWD treatment. Notably, these differential lipid metabolites were particularly involved in biological processes such as cholesterol metabolism, linoleic acid metabolism, glycerolipid metabolism, glycerophospholipid metabolism, insulin resistance, arachidonic acid metabolism, and alpha-linoleic acid metabolism. Importantly, Spearman correlation analyses suggested an association between disturbed gut microbiota and altered lipid metabolites. Moreover, they were also closely associated with the bioactivities of BYHWD to reduce the blood lipid and blood glucose levels. Collectively, these results suggest that BYHWD could meliorate gut microbiota dysbiosis and lipid metabolite alterations induced by the HFD in diabetic rats. These results not only provide a novel perspective on understanding the mechanisms underlying BYHWD bioactivity against T2DM but also suggest the use of advanced systems biology methods to reveal some unknown scientific laws in TCM theories.

3.
Artigo em Inglês | MEDLINE | ID: mdl-25574180

RESUMO

Background. Diabetic patients with chronic kidney disease (CKD) suffer from low quality of life (QOL). We aim to assess the effectiveness of auricular acupressure for QOL improvement in these patients. Materials and Methods. Sixty-two participants were randomly assigned to an auricular or a control arm in a randomized controlled trial. Participants in the auricular arm were instructed to perform auricular acupressure 3-5 times per day for 3 months, when they were receiving conventional treatments. Participants in the control arm received conventional treatments only. The primary outcome was the summarized score of Kidney Disease and Quality of Life Short-Form (KDQOL-SF) at 3 months after randomization. The secondary outcomes included the 36-Item Short Form Health Survey (SF-36), glycosylated hemoglobin (HbA1c), and estimated glomerular filtration rate (eGFR). Results. The summarized KDQOL differed significantly between the acupressure (76.6, 95% CI, 72.2 to 81.0) and the control group (61.8, 95% CI, 57.7 to 65.9). Similar results were found in the SF-36 scores. HbA1c and eGFR were not found to be significantly different between the arms and neither were the adverse events. Conclusion. Auricular acupressure was well tolerated in diabetic patients with chronic kidney diseases receiving hemodialysis. Future research is needed to confirm these results.

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