Anti‑oxidation effect of Genistein in vascular endothelial cell after H<sub>2</sub>O<sub>2</sub> stress

Xu,Kun; Qin,Qingwu; Yao,Ye; Yuan,Lin; Du,Xizi; Zhou,Kai; Wu,Xinyu; Wang,Weijie; Liu,Chi

doi:10.3892/mmr.2023.13125

Anti‑oxidation effect of Genistein in vascular endothelial cell after H₂O₂ stress

Authors:
- Kun Xu
- Qingwu Qin
- Ye Yao
- Lin Yuan
- Xizi Du
- Kai Zhou
- Xinyu Wu
- Weijie Wang
- Chi Liu
View Affiliations

Affiliations: School of Medicine, Hunan Normal University, Changsha, Hunan 410013, P.R. China, Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Physiology, Xiangya School of Medicine, Central South University at Changsha, Changsha, Hunan 410013, P.R. China
Published online on: November 6, 2023 https://doi.org/10.3892/mmr.2023.13125
Article Number: 2

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Atherosclerosis (AS) is a chronic inflammatory disease characterized by increased oxidative injury in vascular endothelial cells. Inhibiting the oxidative damage of vascular endothelial cells can effectively prevent the occurrence and development of AS. Of note, Genistein (GEN; ID no. 5280961) is phytochemical found in legume family which has flavonoid properties with multiple potential biological activities including antioxidant, anti‑inflammatory and anticancer. Antioxidant capacity of GEN has a potential protective effect on vascular endothelial cells after oxidative stress. In the present study, the protective effect of GEN on H2O2‑induced oxidation damage was investigated in human vascular endothelial cells (HUVECs). Following GEN pretreatment of HUVECs, H2O2 was added, and apoptosis was detected by flow cytometry, and the expression of relevant genes and proteins was detected by PCR and westerner blot. The results of the present study revealed that GEN significantly enhanced the cell survival rate and decreased the apoptotic rates of HUVECs after H2O2 stress. Besides, GEN reduced the accumulation of intracellular reactive oxygen species by enhancing activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD) and glutathione peroxidase. Moreover, GEN also inhibited the apoptosis of vascular endothelial cells and enhanced the activation of the nuclear factor erythroid2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1)/SOD pathway. Collectively, it was identified that GEN is an effective antioxidant which can reduce the oxidative damage by H2O2 through the Nrf2/HO‑1/SOD signaling pathway in HUVECs.

View References

1	Libby P: The changing landscape of atherosclerosis. Nature. 592:524–533. 2021. View Article : Google Scholar : PubMed/NCBI
2	Wang W, Liu YN, Yin P, Wang LJ, Liu JM, Qi JL, You JL, Lin L and Zhou MG: Analysis on factors associated with the place of death among individuals with cardiovascular diseases in China, 2018. Zhonghua Liu Xing Bing Xue Za Zhi. 42:1429–1436. 2021.(In Chinese). PubMed/NCBI
3	Zhang W, Huang Q, Zeng Z, Wu J, Zhang Y and Chen Z: Sirt1 inhibits oxidative stress in vascular endothelial cells. Oxid Med Cell Longev. 2017:75439732017. View Article : Google Scholar : PubMed/NCBI
4	Wu Y, Wang Y and Nabi X: Protective effect of Ziziphora clinopodioides flavonoids against H₂O₂-induced oxidative stress in HUVEC cells. Biomed Pharmacother. 117:1091562019. View Article : Google Scholar : PubMed/NCBI
5	Hughes GJ, Ryan DJ, Mukherjea R and Schasteen CS: Protein digestibility-corrected amino acid scores (PDCAAS) for soy protein isolates and concentrate: Criteria for evaluation. J Agric Food Chem. 59:12707–12712. 2011. View Article : Google Scholar : PubMed/NCBI
6	Li P, Yao LY, Jiang YJ, Wang DD, Wang T, Wu YP, Li BX and Li XT: Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway. Ecotoxicol Environ Saf. 227:1128862021. View Article : Google Scholar : PubMed/NCBI
7	Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B and Reed JC: Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 9:1799–1805. 1994.PubMed/NCBI
8	Rahman Mazumder MA and Hongsprabhas P: Genistein as antioxidant and antibrowning agents in in vivo and in vitro: A review. Biomed Pharmacother. 82:379–392. 2016. View Article : Google Scholar : PubMed/NCBI
9	Zhai X, Lin M, Zhang F, Hu Y, Xu X, Li Y, Liu K, Ma X, Tian X and Yao J: Dietary flavonoid genistein induces Nrf2 and phase II detoxification gene expression via ERKs and PKC pathways and protects against oxidative stress in Caco-2 cells. Mol Nutr Food Res. 57:249–259. 2013. View Article : Google Scholar : PubMed/NCBI
10	Qian Y, Guan T, Huang M, Cao L, Li Y, Cheng H, Jin H and Yu D: Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model. Neurochem Int. 60:759–767. 2012. View Article : Google Scholar : PubMed/NCBI
11	Qian Y, Cao L, Guan T, Chen L, Xin H, Li Y, Zheng R and Yu D: Protection by genistein on cortical neurons against oxidative stress injury via inhibition of NF-kappaB, JNK and ERK signaling pathway. Pharm Biol. 53:1124–1132. 2015. View Article : Google Scholar : PubMed/NCBI
12	Park WH: The effect of MAPK inhibitors and ROS modulators on cell growth and death of H₂O₂-treated HeLa cells. Mol Med Rep. 8:557–564. 2013. View Article : Google Scholar : PubMed/NCBI
13	Song T, Xue Z, Zhang Z, Shen X and Li X: Pan-BH3 mimetic S1 exhibits broad-spectrum antitumour effects by cooperation between Bax and Bak. Basic Clin Pharmacol Toxicol. 113:145–151. 2013. View Article : Google Scholar : PubMed/NCBI
14	Zhai X, Zhang C, Zhao G, Stoll S, Ren F and Leng X: Antioxidant capacities of the selenium nanoparticles stabilized by chitosan. J Nanobiotechnology. 15:42017. View Article : Google Scholar : PubMed/NCBI
15	Wang K, Han L, Hong H, Pan J, Liu H and Luo Y: Purification and identification of novel antioxidant peptides from silver carp muscle hydrolysate after simulated gastrointestinal digestion and transepithelial transport. Food Chem. 342:1282752021. View Article : Google Scholar : PubMed/NCBI
16	Wu H, Wang H, Qi F, Xia T, Xia Y, Xu JF and Zhang X: An activatable host-guest conjugate as a nanocarrier for effective drug release through self-inclusion. ACS Appl Mater Interfaces. 13:33962–33968. 2021. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Messina M: Soy foods, isoflavones, and the health of postmenopausal women. Am J Clin Nutr. 100 (Suppl 1):423S–430S. 2014. View Article : Google Scholar : PubMed/NCBI
19	Nathan C and Cunningham-Bussel A: Beyond oxidative stress: An immunologist's guide to reactive oxygen species. Nat Rev Immunol. 13:349–361. 2013. View Article : Google Scholar : PubMed/NCBI
20	Chen XH, Tan Y, Yu S, Lu L and Deng Y: Pinitol protects against ox-low-density lipoprotein-induced endothelial inflammation and monocytes attachment. J Cardiovasc Pharmacol. 79:368–374. 2022. View Article : Google Scholar : PubMed/NCBI
21	Shan R, Liu N, Yan Y and Liu B: Apoptosis, autophagy and atherosclerosis: Relationships and the role of Hsp27. Pharmacol Res. 166:1051692021. View Article : Google Scholar : PubMed/NCBI
22	Yang S and Lian G: ROS and diseases: Role in metabolism and energy supply. Mol Cell Biochem. 467:1–12. 2020. View Article : Google Scholar : PubMed/NCBI
23	Zorov DB, Juhaszova M and Sollott SJ: Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 94:909–950. 2014. View Article : Google Scholar : PubMed/NCBI
24	Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C and Kroemer G: Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 13:1423–1433. 2006. View Article : Google Scholar : PubMed/NCBI
25	Yang X, He T, Han S, Zhang X, Sun Y, Xing Y and Shang H: The role of traditional Chinese medicine in the regulation of oxidative stress in treating coronary heart disease. Oxid Med Cell Longev. 2019:32314242019. View Article : Google Scholar : PubMed/NCBI
26	Sakahira H, Enari M and Nagata S: Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature. 391:96–99. 1998. View Article : Google Scholar : PubMed/NCBI
27	Yanase S, Onodera A, Tedesco P, Johnson TE and Ishii N: SOD-1 deletions in Caenorhabditis elegans alter the localization of intracellular reactive oxygen species and show molecular compensation. J Gerontol A Biol Sci Med Sci. 64:530–539. 2009. View Article : Google Scholar : PubMed/NCBI
28	Forman HJ, Zhang H and Rinna A: Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 30:1–12. 2009. View Article : Google Scholar : PubMed/NCBI
29	Loboda A, Damulewicz M, Pyza E, Jozkowicz A and Dulak J: Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism. Cell Mol Life Sci. 73:3221–3247. 2016. View Article : Google Scholar : PubMed/NCBI
30	Kensler TW, Wakabayashi N and Biswal S: Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 47:89–116. 2007. View Article : Google Scholar : PubMed/NCBI
31	Mitsuishi Y, Motohashi H and Yamamoto M: The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism. Front Oncol. 2:2002012. View Article : Google Scholar : PubMed/NCBI
32	Alam J, Stewart D, Touchard C, Boinapally S, Choi AM and Cook JL: Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem. 274:26071–26078. 1999. View Article : Google Scholar : PubMed/NCBI