Eucommia lignans alleviate the progression of diabetic nephropathy through mediating the AR/Nrf2/HO-1/AMPK axis in vivo and in vitro.
10.1016/S1875-5364(23)60427-3
- Author:
Qi HUANG
1
,
2
,
3
;
Yinfan ZHANG
4
,
5
;
Yueping JIANG
1
,
6
;
Ling HUANG
7
;
Qiong LIU
4
,
8
;
Dongsheng OUYANG
9
,
10
,
11
Author Information
1. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
3. Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 411000, China.
4. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
5. Department of Operating Room, Xiangya Hospital, Central South University, Changsha 410008, China.
6. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
7. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China.
8. Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: liuqiong20160901@163.com.
9. Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 411000, China
10. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China
11. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410028, China. Electronic address: ouyangyj@163.com.
- Publication Type:Journal Article
- Keywords:
Aldose reductase (AR);
Diabetic nephropathy (DN);
Eucommia lignans;
Nrf2/HO-1/AMPK
- MeSH:
Animals;
Rats;
AMP-Activated Protein Kinases/genetics*;
Diabetes Mellitus;
Diabetic Nephropathies/prevention & control*;
Eucommiaceae/metabolism*;
Lignans/therapeutic use*;
Molecular Docking Simulation;
NF-E2-Related Factor 2/metabolism*;
Tandem Mass Spectrometry
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(7):516-526
- CountryChina
- Language:English
-
Abstract:
Lignans derived from Eucommia ulmoides Oliver (Eucommia lignans) inhibit the progression of inflammatory diseases, while their effect on the progression of diabetic nephropathy (DN) remained unclear. This work was designed to assess the function of Eucommia lignans in DN. The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS. The binding between Eucommia lignans and aldose reductase (AR) was predicted by molecular docking. Eucommia lignans (200, 100, and 50 mg·kg-1) were used in model animals to evaluate their renal function changes. Rat glomerular mesangial cells (HBZY-1) were transfected with sh-AR, sh-AMPK, and oe-AR in the presence of high glucose (HG) or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis. Eucommia lignans significantly attenuated the progression of DN in vivo. Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury, while downregulating the levels of Cyto c, caspase 9, AR, and NOX4 in HBZY-1 cells. In contrast, HG-induced downregulation of Nrf2, HO-1 and p-AMPKα levels were abolished by Eucommia lignans. Meanwhile, knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression, and AR overexpression reversed the effect of Eucommia lignans. Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis. Thus, these findings might provide evidence for the use of Eucommia lignans in treating DN.
