Astragaloside IV ameliorates diabetic nephropathy by modulating the mitochondrial quality control network

Abstract

The aim of this study was to investigate the effect and possible mechanism of Astragaloside IV (AS-IV) on retarding the progression of diabetic nephropathy (DN) in a type 2 diabetic animal model, db/db mice. Eight-week-old male db/db diabetic mice and their nondiabetic littermate control db/m mice were used in the present study. AS-IV was administered to the db/db mice by adding it to standard feed at a dose of 1g/kg for 12 weeks. Renal injury was assessed by urinary albumin excretion (UAE) and Periodic acid-Schiff staining. The protein expression levels of mitochondrial quality-control-associated proteins were evaluated using Western blotting and immunohistochemical staining analysis. At the end of the experiment, db/db mice showed overt renal injury, as evidenced by increased UAE, increased urinary N-acetyl-β-D-glucosaminidase (NAG), expansion of mesangial matrix, and increased renal tubular area. AS-IV administration significantly reduced UAE and urinary NAG and ameliorated the renal pathologic injury seen in db/db mice. Furthermore, the expression of dynamin-related protein 1 (Drp-1), mitochondrial fission protein 1 (Fis-1), and mitochondrial fission factor (MFF), the main regulators of mitochondrial fission, was significantly increased in db/db mice. Moreover, PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy was abnormally activated in db/db mice. AS-IV significantly reduced renal Drp-1, Fis-1, and MFF expression and downregulated PINK1/Parkin-mediated mitophagy in db/db mice. However, mitochondrial biogenesis and mitochondrial fusion-associated protein levels were not significantly different between db/m and db/db mice in our study, with or without AS-IV treatment. In conclusion, administration of AS-IV could retard DN progression in type 2 diabetes mice, which might be associated with restoration of the mitochondrial quality control network.

A Renal‐Clearable Duplex Optical Reporter for Real‐Time Imaging of Contrast‐Induced Acute Kidney Injury

“…[22] NAGi sn ormally secreted at al ow concentration (< 0.03 unit/24 h) into urine in mice. [43] However,N AG dramatically increased in renal tubules and urine (0.5 unit/24 h) after administration of nephrotoxic drugs. [44] Note that the signals in NAC-treated mice were comparable to the PBS-treated mice because NACh ad as uperb ROS scavenging ability and protects the kidney against nephrotoxic insult.…”

Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte apoptosis of diabetic nephropathy rats

“… 16 Recently, researchers have found that AS-IV could improve DN through regulating mitochondrial quality control network. 3 AS-IV could reduce the endoplasmic reticulum stress-induced apoptosis of podocytes through upregulating sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA) expression in DN. 17 However, the underlying mechanism of AS-IV in the treatment of DN is not fully revealed.…”

A Renal‐Clearable Duplex Optical Reporter for Real‐Time Imaging of Contrast‐Induced Acute Kidney Injury

“…The ADR offers simultaneous imaging of two interlinked molecular events in the kidneys to detect CIAKI, while the previous single‐channel molecular renal probes failed to do so . NAG is normally secreted at a low concentration (<0.03 unit/24 h) into urine in mice . However, NAG dramatically increased in renal tubules and urine (0.5 unit/24 h) after administration of nephrotoxic drugs .…”