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
. 2022 Aug;247(16):1410-1419.
doi: 10.1177/15353702221106479. Epub 2022 Jul 1.

Epigallocatechin-3-gallate ameliorates renal endoplasmic reticulum stress-mediated inflammation in type 2 diabetic rats

Rui Yang  1 , Jinwu Chen  1   2 , Qiang Jia  3 , Xingxing Yang  1 , Shomaila Mehmood  4
Affiliations

Epigallocatechin-3-gallate ameliorates renal endoplasmic reticulum stress-mediated inflammation in type 2 diabetic rats

Rui Yang et al. Exp Biol Med (Maywood). 2022 Aug.

Abstract

Epigallocatechin-3-gallate (EGCG), an essential polyphenolic constituent found in tea leaves, possesses various potent biological activities. This research was undertaken to investigate the impact of EGCG against endoplasmic reticulum (ER) stress-mediated inflammation and to clarify the underlying molecular mechanism in type 2 diabetic kidneys. The male rats were randomized into four groups: normal, diabetic, low-dose EGCG, and high-dose EGCG. In type 2 diabetic rats, hyperglycemia and hyperlipidemia noticeably caused renal structural damage and dysfunction and aggravated ER stress. Meanwhile, sustained ER stress activated the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and then upregulated the contents of inflammatory cytokines in the diabetic kidney. Following supplementation with 40 mg/kg and 80 mg/kg EGCG, hyperglycemia, hyperlipidemia, and renal histopathological alterations and dysfunction were noticeably ameliorated; renal ER stress, NLRP3 inflammasome, and inflammatory response were markedly repressed in the EGCG treatment groups. In summary, the current study highlighted the renoprotective effects of EGCG in type 2 diabetes and its mechanisms are mainly associated with the repression of ER stress-mediated NLRP3 inflammasome overactivation.

Keywords: Epigallocatechin-3-gallate; NOD-like receptor family pyrin domain containing 3 inflammasome; diabetic nephropathy; endoplasmic reticulum stress; inflammation; rat.

PubMed Disclaimer

Conflict of interest statement

Declaration Of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Effects of EGCG treatment on blood glucose and lipid parameters in type 2 diabetic rats: (A) FBG, (B) GSP, (C) triglycerides, (D) T-CHO, and (E) AGEs. All values were presented as the mean ± SD. **P < 0.01, when compared with NC group. #P < 0.05, ##P < 0.01, when compared with DN group.
Figure 2.
Figure 2.
Effects of EGCG treatment on renal functional indices: (A) 24 h urine volume, (B) 24 h urine protein, (C) sCr, and (D) BUN. All values were presented as the mean ± SD. **P < 0.01, when compared with NC group. #P < 0.05, ##P < 0.01, when compared with DN group.
Figure 3.
Figure 3.
Effects of EGCG treatment on pathological changes in kidney tissue. (A) PAS staining. Scale bar: 30 μm. (B) Ultrastructure. Scale bar: 1 μm. (A color version of this figure is available in the online journal.)
Figure 4.
Figure 4.
Effects of EGCG treatment on KIM1 and IRE1 expression in kidney tissue. (A) Expression of renal KIM1 in IHC assay. (B) Expression of renal IRE1 in IHC assay. Scale bar: 50 μm. All values were presented as the mean ± SD. **P < 0.01, when compared with the NC group. #P < 0.05, ##P < 0.01, when compared with the DN group. (A color version of this figure is available in the online journal.)
Figure 5.
Figure 5.
EGCG treatment decreases the mRNA expression of ER stress markers in kidney tissue of diabetic rats: (A) IRE1, (B) ATF6, (C) PERK, (D) GRP78, and (E) CHOP. All values were presented as the mean ± SD. **P < 0.01, when compared with NC group. #P < 0.05, ##P < 0.01, when compared with DN group.
Figure 6.
Figure 6.
EGCG treatment downregulates renal inflammatory cytokines in type 2 diabetic rats: (A) TNF-α, (B) MCP-1, (C) IL-1β, and (D) IL-18. All values were presented as the mean ± SD. **P < 0.01, when compared with NC group. #P < 0.05, ##P < 0.01, when compared with DN group.
Figure 7.
Figure 7.
Effects of EGCG treatment on IRE1/NLRP3 inflammasome expression in kidney tissue of each group. (A) Western blotting results for renal IRE1, XBP1, NLRP3, and caspase-1 (p20). (B) to (E) Relative expression of IRE1, XBP1, NLRP3, and caspase-1 (p20) proteins in kidney tissue by western blot assay. GAPDH was used as the housekeeping protein. All values were presented as the mean ± SD. **P < 0.01, when compared with NC group. #P < 0.05, ##P < 0.01, when compared with DN group.
See this image and copyright information in PMC

References

    1. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev 2013;93:137–88 - PubMed
    1. Fineberg D, Jandeleit-Dahm KA, Cooper ME. Diabetic nephropathy: diagnosis and treatment. Nat Rev Endocrinol 2013;9:713–23 - PubMed
    1. Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol 2017;12:2032–45 - PMC - PubMed
    1. Kashihara N, Haruna Y, Kondeti VK, Kanwar YS. Oxidative stress in diabetic nephropathy. Curr Med Chem 2010;17:4256–69 - PMC - PubMed
    1. Barrera-Chimal J, Jaisser F. Pathophysiologic mechanisms in diabetic kidney disease: a focus on current and future therapeutic targets. Diabetes Obes Metab 2020;22:16–31 - PubMed

Publication types