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Astragaloside IV ameliorates renal injury in db/db mice
Huili Sun1, Wenjing Wang1, Pengxun Han1
1Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China.
Abstract:
Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-β1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways.
Insights
Astragaloside IV (AS-IV) shows protective effects against type 2 diabetic nephropathy in mice. This natural compound may inhibit key signaling pathways involved in kidney damage.
Area of Science:
- Pharmacology
- Nephrology
- Endocrinology
Background:
- Diabetic nephropathy is a severe complication of diabetes mellitus and a leading cause of chronic kidney disease.
- The Akt/mTOR, NFκB, and Erk1/2 signaling pathways are critically involved in the pathogenesis of diabetic nephropathy.
- Astragaloside IV (AS-IV), derived from Huangqi, has demonstrated renal protective properties in type 1 diabetes models.
Purpose of the Study:
- To investigate the renoprotective effects of dietary Astragaloside IV (AS-IV) supplementation in a mouse model of type 2 diabetic nephropathy (db/db mice).
- To explore the impact of AS-IV on key signaling pathways implicated in diabetic kidney disease.
Main Methods:
- Administration of AS-IV to db/db mice.
- Assessment of renal injury markers including albuminuria, glomerular and tubular pathology, and urinary levels of NAG, NGAL, and TGF-β1.
- Evaluation of the activation status of Akt/mTOR, NFκB, and Erk1/2 signaling pathways.
- Monitoring for potential hepatotoxicity.
Main Results:
- AS-IV administration significantly reduced albuminuria and ameliorated glomerular and tubular pathological changes in db/db mice.
- Urinary markers of kidney damage (NAG, NGAL, TGF-β1) were decreased following AS-IV treatment.
- AS-IV attenuated the activation of the Akt/mTOR, NFκB, and Erk1/2 signaling pathways in the kidneys of diabetic mice.
- No detectable hepatotoxicity was observed with AS-IV supplementation.
Conclusions:
- Dietary supplementation with Astragaloside IV (AS-IV) confers significant benefits for type 2 diabetic nephropathy in a mouse model.
- The renoprotective effects of AS-IV appear to be mediated through the inhibition of the Akt/mTOR, NFκB, and Erk1/2 signaling pathways.
- AS-IV represents a potential therapeutic agent for diabetic kidney disease without causing liver damage.
