Tripterygium glycoside tablet attenuates renal function impairment in diabetic nephropathy mice by regulating triglyceride metabolism

J Pharm Biomed Anal. 2022 Nov 30:221:115028. doi: 10.1016/j.jpba.2022.115028. Epub 2022 Sep 7.

Abstract

Tripterygium glycoside tablet (TGT) has been used clinically to alleviate diabetic nephropathy (DN) for decades. However, the mechanism of its anti-DN has not been fully clarified. The aim of this study was to elucidate molecular mechanism of TGT in repairing renal function injury. The results of biochemical parameters and renal histopathology implied that TGT intervention could attenuate creatinine, albumin excretion rate and histological injury of kidney in DN mouse model. Moreover, UHPLC-QTOF-MS/MS-based untargeted metabolomic analysis indicated that 11 metabolites in kidney of mice with DN were restored after TGT treatment, and the most prominent metabolic alteration was triglyceride (TG) metabolism. Mechanistically, TGT effectively improved the function of impaired kidney by promoting TG catabolism via modulation of adipose triglyceride lipase in DN mice. Our findings identified the link between circulating metabolites and DN, suggesting that it might be a possibility to intervene in DN by targeting metabolism.

Keywords: Adipose triglyceride lipase; Diabetic nephropathy; Renal function impairment; Triglyceride metabolism; Tripterygium glycoside tablet; UHPLC-QTOF-MS/MS.

MeSH terms

  • Albumins
  • Animals
  • Cardiac Glycosides*
  • Creatinine / metabolism
  • Diabetes Mellitus* / metabolism
  • Diabetic Nephropathies* / drug therapy
  • Glycosides / chemistry
  • Glycosides / pharmacology
  • Glycosides / therapeutic use
  • Kidney / metabolism
  • Lipase
  • Mice
  • Renal Insufficiency* / pathology
  • Tablets / metabolism
  • Tandem Mass Spectrometry
  • Triglycerides
  • Tripterygium / chemistry

Substances

  • Albumins
  • Cardiac Glycosides
  • Glycosides
  • Tablets
  • Triglycerides
  • Creatinine
  • Lipase