Cyclocarya paliurus triterpenic acids fraction attenuates kidney injury via AMPK-mTOR-regulated autophagy pathway in diabetic rats.

Abstract

BACKGROUD:

Diabetic nephropathy is the most serious complication of diabetes. Cyclocarya paliurus (CP), an herbal plant in China, has been reported the biological activity of anti-hyperglycemia. However, its effects on the diabetic nephropathy (DN) remain unclear.

PURPOSE:

We aimed to investigate the potential role of CP and its underlying mechanisms on DN.

STUDY DESIGN:

In this study, the effects of triterpenic acids-enriched fraction from CP (CPT) on DN was evaluated in streptozotocin (STZ)-induced rats and high glucose (HG)-induced HK-2 cells models.

METHODS:

After oral administration with or without CPT for 10 weeks, body weight, glucose, microalbumin, serum creatinine and blood urea in STZ-induced rats were detected. Histological analysis was performed to evaluate renal function of mice. Moreover, the level of autophagy was detected by western blot or immunostaining. In vitro, HG-induced HK-2 cell was conducted to evaluate the renal protection and mechanism of CPT.

RESULTS:

CPT dramatically decreased the levels of microalbumin, serum creatinine and blood urea nitrogen and ameliorated increased mesangial matrix and glomerular fibrosis. In addition, we found the CPT prevented renal damage and cell apoptosis through the autophagy. Furthermore, CPT could increase the phosphorylation of AMPK and decrease its downstream effector phosphorylation of mTOR. Besides, the expression of LC3-II were locked by AMPK inhibitor dorsomorphin dihydrochloride (compound C), implying that the autophagy may be regulated with AMPK activation.

CONCLUSION:

These findings suggested that CPT might be a desired candidate against diabetes, potentially through AMPK-mTOR-regulated autophagy pathway.

• Authors: Xuan-Xuan Zhang, Cui-Hua Jiang, Yao Liu, Dong-Xiao Lou, Ya-Ping Huang, Meng Gao, Jian Zhang, Zhi-Qi Yin, Ke Pan
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 64 Pg. 153060 (Nov 2019) ISSN: 1618-095X [Electronic] Germany
• PMID: 31401495 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier GmbH. All rights reserved.

Chemical References

• Blood Glucose
• Drugs, Chinese Herbal
• Streptozocin
• Creatinine
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Blood Glucose (analysis)
• Creatinine (blood)
• Diabetes Mellitus, Experimental (chemically induced, drug therapy, physiopathology)
• Diabetic Nephropathies (chemically induced, drug therapy, physiopathology)
• Drugs, Chinese Herbal
• Juglandaceae (chemistry)
• Kidney (drug effects, physiopathology)
• Kidney Glomerulus (drug effects, physiopathology)
• Male
• Mice
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Streptozocin (pharmacology)
• TOR Serine-Threonine Kinases (metabolism)