Lei Ji1,
Xue Zhong1,
Xingxing Xia2,
Wei Yu1,
Yuping Qin2
1Department of Nephrology, Chongqing General Hospital, Chongqing 400014;
2Department of Nephrology, Affiliated Rich Hospital of Nantong University, Nantong City, Jiangsu Province 226010, China.
For correspondence:- Yuping Qin
Email: qinyupingqyp666@163.com Tel:+8651385969846
Accepted: 28 January 2021
Published: 28 February 2021
Citation:
Ji L, Zhong X, Xia X, Yu W, Qin Y.
Protective effect of syringaresinol on rats with diabetic nephropathy via regulation of Nrf2/HO-1 and TGF-β1/Smads pathways. Trop J Pharm Res 2021; 20(2):275-280
doi:
10.4314/tjpr.v20i2.8
© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Abstract
Purpose: To investigate the protective role of syringaresinol in a rat model of diabetic nephropathy (DN).
Methods: Streptozotocin was injected intraperitoneally into rats to establish the diabetic model. Streptozotocin-induced rats were orally administered syringaresinol, and pathological changes in kidneys were assessed using hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine kidney injury indicators, 24-h urine proteins, blood urea nitrogen (BUN), and serum creatinine (SCR). Blood glucose was measured using a blood glucose meter, while levels of malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) in kidney were also measured using ELISA.
Results: Pathological changes in the kidneys were observed in rats post-streptozotocin treatment. Administration of syringaresinol reduced the lesion degree, with improved pathological morphology in kidney. Syringaresinol administration significantly attenuated streptozotocin-increased levels of BUN, SCR, 24-h urine protein, and blood glucose (p < 0.01). Streptozotocin-induced oxidative stress, shown by enhanced MDA level and reduced levels of SOD, CAT, and GSH-PX, was reversed in rat kidneys following syringaresinol administration. However, the expression levels of nuclear factor erythropoietin-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) proteins decreased, while transforming growth factor-beta 1 (TGF-β1) and signal transducer and transcriptional modulator (Smad) 2/3/7 proteins increased in rats post-streptozotocin treatment. Syringaresinol administration reversed the effects of streptozotocin on protein expression of Nrf2, HO-1, TGF-β1, and Smad 2/3/7.
Conclusion: Syringaresinol exerted a protective effect against DN through activation of Nrf2 and inactivation of TGF?β1/Smad pathways. Thus, the compound can potentially be developed for management of diabetic nephropathy.
Keywords: Syringaresinol, Streptozotocin, Diabetic nephropathy, TGF-?1/Smad, Oxidative stress, Nrf2/HO-1