Abstract Title:

Carnosic acid improves diabetic nephropathy by activating Nrf2/ARE and inhibition of NF-κB pathway.

Abstract Source:

Phytomedicine. 2018 Aug 1 ;47:161-173. Epub 2018 Apr 17. PMID: 30166101

Abstract Author(s):

Zhisheng Xie, Lingjun Zhong, Yanrao Wu, Xiaomeng Wan, Hua Yang, Xiaojun Xu, Ping Li

Article Affiliation:

Zhisheng Xie


BACKGROUND: Diabetic nephropathy (DN), one of the most serious complications of diabetes, is the leading cause of morbidity and mortality of end-stage renal disease. Our previous research found that carnosic acid (CA) or rosemary extract can effectively improve glucose and lipid metabolism disorder by inhibiting SREBPs.

PURPOSE: In this study, we aimed to explore the therapeutic effects of CA on the DN.

METHODS: The mice glomerular mesangial cells (mGMCs) were used to evaluate the anti-oxidative and anti-inflammation effects of CA under high glucose (HG) condition. Furthermore, db/db mice and streptozotocin (STZ)-induced diabetic mice were used to investigate the effects of CA against DN in vivo.

RESULTS: The results showed that CA activated Nrf2, inhibited NF-κB pathway and regulated related downstream genes in mGMC under HG condition. A 14-week treatment of mice with CA reduced water uptake and urine volume, attenuated diabetes-induced albuminuria, increased urine creatinine, and subsequently improved the glomerular sclerosis and mesangial expansion indb/db mice. Similarly, a 20-week oral administration of CA improved kidney damage in STZ-induced diabetic mice. In addition, CA inhibited the expression of profibrotic factors, such as TGF-β1, fibronectin and E-cadherin. Compared to irbesartan, CA exerted better glucose lowering effect, and in kidney, CA was more potent to reduce fibronectin and E-cadherin expression. In all the animal experiment, CA did not lead to abnormal damages to other tissues.

CONCLUSION: These findings suggest that CA is a safe compound which exerts the protective effects on diabetes-induced kidney complications.

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