image: PPAR signaling pathway (A); PPARα-involved signaling pathways by KEGG enrichment analysis (B). Results of molecular dynamics simulations about root mean square deviation (RMSD) (C), root mean square fluctuation (RMSF) (D), complex trajectory diagrams and RMSF values (E), solvent accessible surface area (SASA) (F), radius of gyration (Rg) (G), number of hydrogen bonds (H), 3D (I) and 2D (J) landscape maps on free energy. PPARα-abscisic acid on the left side of each subfigure, and PPARα-matricin on the right side of each subfigure for C-J.
Credit: Zi-Jie Yan, Lin Zhang, Xin-Yao Han, Yu Kang, Shu-Man Liu, Tian-Peng Ma, Man Xiao, Yi-Qiang Xie
Diabetic kidney disease (DKD) is a highly prevalent microvascular complication caused by diabetes mellitus and the leading cause of end-stage renal disease. Alpiniae oxyphyllae Fructus (AOF) has been widely used for the treatment of chronic glomerulonephritis, nephrotic syndrome, and other kidney diseases. It is an effective candidate for improving renal lipid deposition in patients with DKD. This experiment aimed to investigate whether AOF could ameliorate lipid deposition by modulating the expression of PPARα in DKD mice and HK-2 cells under high glucose conditions.
The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis, molecular docking, and molecular dynamics simulation. The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells. Cell viability and lipid accumulation were detected by CCK8 and oil red O staining. The expressions of PPARα and fatty acid oxidation-related genes (ACOX1 and CPT1A) were detected by RT-qPCR, Western blot, and immunofluorescence. Furthermore, PPARα knockdown was performed to examine the molecular mechanism of AOF in treating DKD.
Network pharmacological enrichment analysis, molecular docking, and molecular dynamics simulation showed that the active compounds in AOF targeted PPARα and thus transcriptionally regulated ACOX1 and CPT1A. AOF lowered blood glucose, improved dyslipidemia, and attenuated renal injury in DKD mice. AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation. Additionally, it significantly upregulated the expression of PPARα, ACOX1, and CPT1A in both in vivo and in vitro experiments, which was reversed by PPARα knockdown.
AOF may promote fatty acid oxidation via PPARα to ameliorate renal lipid deposition in DKD.
The work entitled “Alpiniae oxyphyllae Fructus ameliorates renal lipid accumulation in diabetic kidney disease via activating PPARα” was published on Asian Pacific Journal of Tropical Biomedicine (published on Jan. 17, 2025).
Journal
Asian Pacific Journal of Tropical Biomedicine
Method of Research
Experimental study
Subject of Research
Cells
Article Title
Alpiniae oxyphyllae Fructus ameliorates renal lipid accumulation in diabetic kidney disease via activating PPARα
Article Publication Date
17-Jan-2025