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. 2024 Dec;55(6):1327-1339.
doi: 10.1007/s10735-024-10273-7. Epub 2024 Nov 9.

Gastrodin ameliorates diabetic nephropathy by activating the AMPK/Nrf2 pathway

Shuqin Zhao #  1 , Qingyun Pan #  2 , Xiaolin Lin #  3 , Xian Li #  3 , Li Qu  4
Affiliations

Gastrodin ameliorates diabetic nephropathy by activating the AMPK/Nrf2 pathway

Shuqin Zhao et al. J Mol Histol. 2024 Dec.

Abstract

Diabetic nephropathy (DN) is a leading cause of end-stage kidney failure, contributing to elevated morbidity and mortality rates in individuals with diabetes. Despite its potential renoprotective effects, the molecular mechanism by which gastrodin (GSTD) impacts DN remains unclear. To investigate this, mice were initially induced with DN via intraperitoneal streptozotocin (STZ) injection (50 mg/kg) and subsequently treated with varying doses of GSTD (5, 10, 20 mg/kg). Furthermore, the potential molecular mechanism of GSTD in mitigating DN was explored in vivo in conjunction with compound C, an inhibitor of 5'-AMP-activated protein kinase (AMPK). Subsequently, the blood weight, fasting blood glucose levels, and renal injury markers of DN-afflicted mice were assessed. Additionally, renal tissues were subjected to quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) to evaluate inflammatory factor levels, colorimetric assays to measure renal malondialdehyde (MDA) levels, and immunoblotting analysis to examine AMPK/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. The results demonstrated that a 6-week GSTD regimen effectively improved metabolic manifestations associated with DN, including reductions in fasting blood glucose levels, 24-hour urine output, renal indices, amelioration of glomerular histopathological abnormalities, diminished glycogen accumulation, and fibrosis. Furthermore, DN-afflicted renal tissues exhibited decreased MDA levels and elevated expression of AMPK/Nrf2 pathway-associated proteins. The beneficial effects of GSTD on DN and its protein modulation were reversed upon co-intervention with compound C. Together, our findings imply that GSTD improves DN by activating the AMPK/Nrf2 pathway, thereby mitigating STZ-induced renal damage, inflammatory responses, and oxidative stress.

Keywords: AMPK/Nrf2 pathway; Diabetic nephropathy; Inflammatory response; Oxidative stress; Tensin.

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Conflict of interest statement

Declarations Ethics approval and consent for participation Each animal experimental procedure gained approval from Animal Ethics Committee of Yantai Yuhuangding hospital The animal-related experiments were conducted following the Guide for the Care and Use of Laboratory Animals from the National Institute of Health (NIH). Consent for publication Not applicable. Competing interests The authors declare no competing interests.

References

    1. Allen DA, Harwood S, Varagunam M, Raftery MJ, Yaqoob MM (2003) High glucose-induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases. FASEB J 17(8):908–910 - PubMed
    1. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6):1615–1625 - PubMed
    1. Chang CC, Chang CY, Wu YT, Huang JP, Yen TH, Hung LM (2011) Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, pro-inflammatory cytokines, and AMP-activated protein kinase. J Biomed Sci 18(1):47 - PubMed - PMC
    1. Cheng Y, Qi Y, Liu S et al (2020) C1q/TNF-related protein 9 inhibits high glucose-induced oxidative stress and apoptosis in retinal pigment epithelial cells through the activation of AMPK/Nrf2 signaling pathway. Cell Transpl. ;29(963689720962052)
    1. Danesh FR, Sadeghi MM, Amro N et al (2002) 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of rho GTPase/p21 signaling pathway: implications for diabetic nephropathy. Proc Natl Acad Sci USA 99(12):8301–8305 - PubMed - PMC

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