Effects of berberine on expression of FXR and SHP in kidney of mice with diabetic nephropathy
- VernacularTitle:小檗碱对糖尿病肾病小鼠肾脏中FXR和SHP表达的影响
- Author:
Li-Juan DENG
1
;
Jie-Yao HUANG
;
Yan-Jun HU
;
Wei CUI
;
Wei FANG
;
Ya-Ping XIAO
Author Information
- Keywords: berberine; diabetic nephropathy; tran-scriptomics; molecular dynamics simulation; farnesoid X receptor; small heterodimer partner
- From: Chinese Pharmacological Bulletin 2024;40(12):2269-2276
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the ameliorative effects of berberine(BBR)on diabetic nephropathy(DN)in mice and investigate its potential mechanisms through transcriptomic analysis.Methods 8-week-old db/db mice were randomly assigned into four groups:model group(DN group),BBR 50 mg·kg-1 group(BBR-L group),BBR 100 mg·kg-1 group(BBR-H group),and empagliflozin 10 mg·kg-1 group(EMPA group).Age-matched db/m mice were used as the control group(NC group),with eight mice in each group.Each group received intragastric administration once daily for eight weeks.After the treatment,serum,u-rine,and kidney samples were collected to evaluate re-nal function indicators and observe renal pathological changes.Differentially expressed genes(DEGs)in kidney tissue were identified through transcriptomic a-nalysis,followed by KEGG and GO enrichment analy-sis.Potential targets were further validated using mo-lecular docking,molecular dynamics simulations,West-ern blot,and immunohistochemistry.Results Both BBR and EMPA significantly reduced fasting blood glu-cose levels in DN mice,improved renal function,and alleviated renal injury and fibrosis.Compared to the NC group,855 DEGs were identified in the DN group,while 194 DEGs were identified in the BBR-H group compared to the DN group.KEGG enrichment analysis indicated that the mechanisms underlying BBR's effects on DN were primarily related to type 1 diabetes and bile secretion pathways.Molecular docking results demonstrated a strong binding affinity between BBR and FXR and a moderate binding affinity with SHP.Molecular dynamics simulations corroborated the doc-king results.FXR and SHP protein expression signifi-cantly decreased in the DN group compared to the NC group.At the same time,BBR treatment significantly increased the expression of these proteins compared to the DN group.Conclusion BBR may mitigate DN-in-duced renal injury by modulating bile acid and lipid homeostasis through the FXR-SHP pathway.
