https://doi.org/10.4081/ejh.2024.4140

Effect of Danggui Buxue decoction on hypoxia-induced injury of retinal Müller cells in vitro

Vol. 68 No. 4 (2024)
Submitted: 10 September 2024
Accepted: 29 October 2024
Published: 25 November 2024
Danggui Buxue decoction, hypoxia, retinal Müller cells, diabetic retinopathy, ATF4/CHOP pathway
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Authors

Xilin Ge
Diabetes Research Institute, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen; Geriatric Department, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
Caoxin Huang
Diabetes Research Institute, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Wenting Chen
Diabetes Research Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Chen Yang
Diabetes Research Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Wenfang Huang
Diabetes Research Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Jia Li
Diabetes Research Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Shuyu Yang
gexilin@aliyun.com
Traditional Chinese Medicine Studio, The First Affiliated Hospital of Xiamen University, Xiamen; Integrated Traditional Chinese and Western Medicine Center, School of Medicine, Xiamen University, Xiamen, China.

Retinopathy is a common complication of diabetes mellitus and the leading cause of visual impairment. Danggui Buxue decoction (RRP) has been used as a traditional drug for the treatment of diabetic nephropathy for many years. The aim of this study was to investigate the effects of RRP on hypoxia-induced retinal Müller cell injury. A model of retinal Müller cell damage was created using high glucose levels (25 mmol/L) and/or exposure to low oxygen conditions (1% O2). RRP was given to rats by continuous gavage for 7 days to obtain drug-containing serum. After sterilization, the serum was added to the culture medium at a ratio of 10%. Cell viability, apoptosis, and cell proliferation were assessed using the CCK-8 kit, Annexin V-FITC/propidium iodide apoptosis kit, and EdU kit. The mRNA levels of angiogenesis factors (ANGPTL4, VEGF) and inflammatory factors (IL-1B, ICAM-1) were detected by RT-qPCR. Western blot analysis was employed to assess the levels of proteins related to the ATF4/CHOP pathway. Following hypoxia for 48 h and 72 h, there was a significant decrease in cell viability and proliferation, as well as a notable increase in apoptosis compared to the control group (21% O2). However, high glucose stimulation had no significant effect, and high glucose combined with hypoxia had no further damage to cells. After 48 h of exposure to low oxygen levels, the mRNA expression levels of ANGPTL4, VEGF, IL-1B, and ICAM-1 in retinal Müller cells were significantly higher than in the control group (21% O2). RRP treatment significantly alleviated the increase of cell apoptosis and the upregulation of IL-1B and-1 in retinal Müller cells induced by hypoxia. RRP has the potential to reduce the suppression of the ATF4/CHOP pathway in hypoxia-induced retinal Müller cells, and it significantly alleviates cell apoptosis through regulating inflammatory factors and the ATF4/CHOP pathway.

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Scopus
Google Scholar
Europe PMC
1. GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2023;402:203-34. Erratum in Lancet 2023;402:1132.
2. Basri NI, Mahdy ZA, Ahmad S, Abdul KA, Shan LP, Abdul MM, et al. The World Health Organization (WHO) versus The International Association of Diabetes and Pregnancy Study Group (IADPSG) diagnostic criteria of gestational diabetes mellitus (GDM) and their associated maternal and neonatal outcomes. Horm Mol Biol Clin I 2018;34:20170077. DOI: https://doi.org/10.1515/hmbci-2017-0077
3. Sen S, Chakraborty R. Treatment and diagnosis of diabetes mellitus and its complication: advanced approaches. Mini-Rev Med Chem 2015;15:1132-3. DOI: https://doi.org/10.2174/138955751514151006154616
4. Fong DS, Aiello LP, Ferris FR, Klein R. Diabetic retinopathy. Diabetes Care 2004;27:2540-53. DOI: https://doi.org/10.2337/diacare.27.10.2540
5. Simo R, Hernandez C. Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends Endocrin Met 2014;25:23-33. DOI: https://doi.org/10.1016/j.tem.2013.09.005
6. Stem MS, Gardner TW. Neurodegeneration in the pathogenesis of diabetic retinopathy: molecular mechanisms and therapeutic implications. Curr Med Chem 2013;20:3241-50. DOI: https://doi.org/10.2174/09298673113209990027
7. Barber AJ. A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuro-Psychoph 2003;27:283-90. DOI: https://doi.org/10.1016/S0278-5846(03)00023-X
8. Lieth E, Gardner TW, Barber AJ, Antonetti DA. Retinal neurodegeneration: early pathology in diabetes. Clin Exp Ophthalmol 2000;28:3-8. DOI: https://doi.org/10.1046/j.1442-9071.2000.00222.x
9. Jing G, Wang JJ, Zhang SX. ER stress and apoptosis: a new mechanism for retinal cell death. Exp Diabetes Res 2012;2012:589589. DOI: https://doi.org/10.1155/2012/589589
10. Szegezdi E, Logue SE, Gorman AM, Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. Embo Rep 2006;7:880-5. DOI: https://doi.org/10.1038/sj.embor.7400779
11. Xie Y, E J, Cai H, Zhong F, Xiao W, Gordon RE, et al. Reticulon-1A mediates diabetic kidney disease progression through endoplasmic reticulum-mitochondrial contacts in tubular epithelial cells. Kidney Int 2022;102:293-306. DOI: https://doi.org/10.1016/j.kint.2022.02.038
12. Li J, Wang JJ, Zhang SX. Preconditioning with endoplasmic reticulum stress mitigates retinal endothelial inflammation via activation of X-box binding protein 1. J Biol Chem 2011;286:4912-21. DOI: https://doi.org/10.1074/jbc.M110.199729
13. Wang M, Li Y, Li S, Lv J. Endothelial dysfunction and diabetic cardiomyopathy. Front Endocrinol 2022;13:851941. DOI: https://doi.org/10.3389/fendo.2022.851941
14. Wang XZ, Ron D. Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP kinase. Science 1996;272:1347-9. DOI: https://doi.org/10.1126/science.272.5266.1347
15. Gao Z, Li M, Yao F, Xia X, Duan T, Meng J, et al. Valdecoxib protects against cell apoptosis induced by endoplasmic reticulum stress via the inhibition of PERK-ATF4-CHOP pathway in experimental glaucoma. Int J Mol Sci 2022;23:12983. DOI: https://doi.org/10.3390/ijms232112983
16. Abcouwer SF, Gardner TW. Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. Ann NY Acad Sci 2014;1311:174-90. DOI: https://doi.org/10.1111/nyas.12412
17. Rattner A, Williams J, Nathans J. Roles of HIFs and VEGF in angiogenesis in the retina and brain. J Clin Invest 2019;129:3807-20. DOI: https://doi.org/10.1172/JCI126655
18. Zeng K, Xu H, Chen K, Zhu J, Zhou Y, Zhang Q, et al. Effects of taurine on glutamate uptake and degradation in Muller cells under diabetic conditions via antioxidant mechanism. Mol Cell Neurosci 2010;45:192-9. DOI: https://doi.org/10.1016/j.mcn.2010.06.010
19. Hua YL, Ma Q, Yuan ZW, Zhang XS, Yao WL, Ji P, et al. A novel approach based on metabolomics coupled with network pharmacology to explain the effect mechanisms of Danggui Buxue Tang in anaemia. Chin J Nat Med 2019;17:275-90. DOI: https://doi.org/10.1016/S1875-5364(19)30031-7
20. Zhang Y, Jiang L, Xue J, Lv M, Zhang W. The efficacy and potential mechanism of Danggui Buxue decoction in treating diabetic nephropathy: A meta-analysis and network pharmacology. Medicine 2023;102:e33481. DOI: https://doi.org/10.1097/MD.0000000000033481
21. Zhang R, Han X, Huang T, Wang X. Danggui buxue tang inhibited mesangial cell proliferation and extracellular matrix accumulation through GAS5/NF-kappaB pathway. Bioscience Rep 2019;39:BSR2018174. DOI: https://doi.org/10.1042/BSR20181740
22. Ke HL, Zhang YW, Zhou BF, Zhen RT. Effects of Danggui Buxue Tang, a traditional Chinese herbal decoction, on high glucose-induced proliferation and expression of extracellular matrix proteins in glomerular mesangial cells. Nat Prod Res 2012;26:1022-6. DOI: https://doi.org/10.1080/14786419.2010.546796
23. Ceker T, Yilmaz C, Kirimlioglu E, Aslan M. Endoplasmic-reticulum-stress-induced lipotoxicity in human kidney epithelial cells. Toxicol Res-Uk 2022;11:683-95. DOI: https://doi.org/10.1093/toxres/tfac041
24. Saint-Geniez M, Maharaj AS, Walshe TE, Tucker BA, Sekiyama E, Kurihara T, et al. Endogenous VEGF is required for visual function: evidence for a survival role on Muller cells and photoreceptors. PloS One 2008;3:e3554. DOI: https://doi.org/10.1371/journal.pone.0003554
25. Li Y, Zhang F, Nagai N, Tang Z, Zhang S, Scotney P, et al. VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats. J Clin Invest 2008;118:913-23. DOI: https://doi.org/10.1172/JCI33673
26. Nishijima K, Ng YS, Zhong L, Bradley J, Schubert W, Jo N, et al. Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol 2007;171:53-67. DOI: https://doi.org/10.2353/ajpath.2007.061237
27. Ola MS, Nawaz MI, Khan HA, Alhomida AS. Neurodegeneration and neuroprotection in diabetic retinopathy. Int J Mol Sci 2013;14:2559-72. DOI: https://doi.org/10.3390/ijms14022559
28. Bringmann A, Pannicke T, Grosche J, Francke M, Wiedemann P, Skatchkov SN, et al. Muller cells in the healthy and diseased retina. Prog Retin Eye Res 2006;25:397-424. DOI: https://doi.org/10.1016/j.preteyeres.2006.05.003
29. Toft-Kehler AK, Gurubaran IS, Desler C, Rasmussen LJ, Skytt DM, Kolko M. Oxidative stress-induced dysfunction of Muller cells during starvation. Invest Ophth Vis Sci 2016;57:2721-8. DOI: https://doi.org/10.1167/iovs.16-19275
30. Bringmann A, Wiedemann P. Muller glial cells in retinal disease. Ophthalmologica 2012;227:1-19. DOI: https://doi.org/10.1159/000328979
31. Vecino E, Rodriguez FD, Ruzafa N, Pereiro X, Sharma SC. Glia-neuron interactions in the mammalian retina. Prog Retin Eye Res 2016;51:1-40. DOI: https://doi.org/10.1016/j.preteyeres.2015.06.003
32. Zhang P, Yan X, Zhang X, Liu Y, Feng X, Yang Z, et al. TMEM215 prevents endothelial cell apoptosis in vessel regression by blunting BIK-regulated ER-to-mitochondrial Ca influx. Circ Res 2023;133:739-57. DOI: https://doi.org/10.1161/CIRCRESAHA.123.322686
33. Zhong Y, Li J, Chen Y, Wang JJ, Ratan R, Zhang SX. Activation of endoplasmic reticulum stress by hyperglycemia is essential for Muller cell-derived inflammatory cytokine production in diabetes. Diabetes 2012;61:492-504. DOI: https://doi.org/10.2337/db11-0315

Ethics Approval

this study was approved by the Ethics Committee of Xiamen University

How to Cite

Ge, X., Huang, C., Chen, W., Yang, C., Huang, W., Li, J., & Yang, S. (2024). Effect of Danggui Buxue decoction on hypoxia-induced injury of retinal Müller cells <i>in vitro</i>. European Journal of Histochemistry, 68(4). https://doi.org/10.4081/ejh.2024.4140
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