Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep;8(18):1154.
doi: 10.21037/atm-20-5811.

Ligustilide alleviates podocyte injury via suppressing the SIRT1/NF-κB signaling pathways in rats with diabetic nephropathy

Feng Xu  1 , Zi Ye  1 , Shuo Tao  2 , Wangshu Liu  3 , Jianbing Su  3 , Xingxing Fang  3 , Xueqin Wang  3
Affiliations

Ligustilide alleviates podocyte injury via suppressing the SIRT1/NF-κB signaling pathways in rats with diabetic nephropathy

Feng Xu et al. Ann Transl Med. 2020 Sep.

Abstract

Background: Diabetic nephropathy (DN) is one of the common chronic microvascular complications of diabetes, and podocyte injury and dysfunction are strictly related to the pathogenesis of DN. Studies have shown that ligustilide (LIG) has anti-inflammatory, antioxidant, and anti-apoptotic activities. This study was designed to investigate the therapeutic effect of LIG in DN rats and their mechanisms.

Methods: DN rat models (n=10) were induced by streptozotocin (STZ) combined with a high-fat diet. Rats in the LIG group were intragastrically administered with LIG daily for eight weeks, and animals in the positive control group were treated with Losartan potassium. The body weight and blood glucose were checked weekly during the treatment. The pathological changes of kidney tissue were observed with hematoxylin and eosin (HE) staining. Blood lipid profiles and renal function-related markers, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), and serum creatinine (Scr) were monitored using a biochemical analyzer. The protein expression of nephrin was determined by immunohistochemistry and Western blotting. Finally, Western blot was used to determine the protein expression of Sirtuin 1 (SIRT1) and nuclear factor-kappa B (NF-κB).

Results: Compared with the healthy control group, rats in the DN group have slower weight gain, increased blood sugar level, renal lesions, and impaired renal function, along with decreased nephrin expression, abnormally activated NF-κB, and inhibited SIRT1 protein expression. All the above conditions were improved after intervention with either losartan potassium or LIG.

Conclusions: LIG attenuates podocyte injury by regulating the SIRT1/NF-κB signaling pathway and thereby exerts its protective effect on renal function in DN rats.

Keywords: Ligustilide (LIG); Sirtuin 1/nuclear factor-kappa B signaling pathway (SIRT1/NF-κB signaling pathway); diabetic nephropathy (DN); podocyte injury.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5811). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Effects of different treatments on body weight and blood glucose level. ##, P<0.01 vs. control; *, P<0.05, **, P<0.01 vs. model.
Figure 2
Figure 2
Effects of different treatments on renal histopathology and function in rats. ###, P<0.001 vs. control; *, P< 0.05, **, P<0.01, ***, P<0.001 vs. model.
Figure 3
Figure 3
Effects of different treatments on nephrin expression in rat kidney tissue. ###, P<0.001 vs. control; *, P<0.05, **, P<0.01 vs. model.
Figure 4
Figure 4
Effects of different treatments on the SIRT1/NF-κB signaling pathways. SIRT1/NF-Κb, Sirtuin 1/nuclear factor-kappa B signaling pathway. ##, P<0.01, ###, P<0.001 vs. control; *, P<0.05, **, P<0.01 vs. model.
See this image and copyright information in PMC

References

    1. Li SY, Huang PH, Tarng DC, et al. Four-and-a-Half LIM Domains Protein 2 Is a Coactivator of Wnt Signaling in Diabetic Kidney Disease. J Am Soc Nephrol 2015;26:3072-84. 10.1681/ASN.2014100989 - DOI - PMC - PubMed
    1. Soler MJ, Batlle D. Single-cell RNA profiling of glomerular cells in diabetic kidney: a step forward for understanding diabetic nephropathy. Ann Transl Med 2019;7:S340. 10.21037/atm.2019.09.104 - DOI - PMC - PubMed
    1. Ziyadeh FN, Wolf G. Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev 2008;4:39-45. 10.2174/157339908783502370 - DOI - PubMed
    1. Mandache E, Penescu M. Nanostructural features of diabetic podocytopathy. Rom J Morphol Embryol 2012;53:23-27. - PubMed
    1. Dai HY, Zheng M, Tang RN, et al. Effects of angiotensin receptor blocker on phenotypic alterations of podocytes in early diabetic nephropathy. Am J Med Sci 2011;341:207-14. 10.1097/MAJ.0b013e3182010da9 - DOI - PubMed