The protective effect of puerarin on angiotensin II‑induced aortic aneurysm formation by the inhibition of NADPH oxidase activation and oxidative stress‑triggered AP‑1 signaling pathways

Yue,Jie; Chang,Shunwu; Xiao,Zhanxiang; Qi,Youfei; He,Jianxing

doi:10.3892/ol.2018.9021

The protective effect of puerarin on angiotensin II‑induced aortic aneurysm formation by the inhibition of NADPH oxidase activation and oxidative stress‑triggered AP‑1 signaling pathways

Authors:
- Jie Yue
- Shunwu Chang
- Zhanxiang Xiao
- Youfei Qi
- Jianxing He
View Affiliations

Affiliations: The First Clinical College, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Gastrointestinal Surgery, Hainan Provincial People's Hospital, Guangzhou, Guangdong 510120, P.R. China, Department of Vascular Surgery, Hainan Provincial People's Hospital, Guangzhou, Guangdong 510120, P.R. China
Published online on: June 26, 2018 https://doi.org/10.3892/ol.2018.9021
Pages: 3327-3332

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

Puerarin, an active ingredient of Pueraria lobata, has a range of pharmacological effects and excellent pharmacodynamic properties. In the present study, the effect of puerarin on angiotensin II‑induced aortic aneurysm formation and the potential underlying molecular mechanisms were examined. The results revealed that puerarin significantly suppressed the viability, and induced the apoptosis, of aneurysm‑inducing cells in a time‑ and dose‑dependent manner. Furthermore, treatment with puerarin significantly suppressed the production of reactive oxygen species (ROS) and the expression of matrix metalloproteinase‑2 (MMP‑2) protein in aneurysm cells. Puerarin treatment significantly increased caspase‑9 and ‑3 activity, induced the protein expression of phosphorylated (p)‑Jun and inhibited the protein expression of activator protein 1 (AP‑1) in aneurysm cells. It was also demonstrated that Puerarin significantly suppressed the reduced nicotinamide‑adenine dinucleotide phosphate (NADPH) oxidase activity in aneurysm cells. Therefore, it was demonstrated that puerarin on suppressed the cell growth of angiotensin II‑induced aortic aneurysm formation by affecting the rate of apoptosis, the generation of ROS, MMP‑2, AP‑1 and p‑Jun protein expression and NADPH oxidase.

View Figures

View References

1	Hansen Lyck M, Thomsen Dahl M, Rasmussen LM and Lindholt JS: Abdominal aortic aneurysm, arterial stiffening and the role of the intraluminal thrombus. Vasa. 44:349–353. 2015. View Article : Google Scholar : PubMed/NCBI
2	Barakat HM, Shahin Y, Barnes R, Gohil R, Souroullas P, Khan J, McCollum PT and Chetter IC: Supervised exercise program improves aerobic fitness in patients awaiting abdominal aortic aneurysm repair. Ann Vasc Surg. 28:74–79. 2014. View Article : Google Scholar : PubMed/NCBI
3	Nienaber CA, Kische S, Rousseau H, Eggebrecht H, Rehders TC, Kundt G, Glass A, Scheinert D, Czerny M, Kleinfeldt T, et al: Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial. Circ Cardiovasc Interv. 6:407–416. 2013. View Article : Google Scholar : PubMed/NCBI
4	United Kingdom EVAR Trial Investigators, . Greenhalgh RM, Brown LC, Powell JT, Thompson SG and Epstein D: Endovascular repair of aortic aneurysm in patients physically ineligible for open repair. N Engl J Med. 362:1872–1880. 2010. View Article : Google Scholar : PubMed/NCBI
5	Wong YY, Flicker L, Yeap BB, McCaul KA, Hankey GJ and Norman PE: Is hypovitaminosis D associated with abdominal aortic aneurysm, and is there a dose-response relationship? Eur J Vasc Endovasc Surg. 45:657–664. 2013. View Article : Google Scholar : PubMed/NCBI
6	Cafueri G, Parodi F, Pistorio A, Bertolotto M, Ventura F, Gambini C, Bianco P, Dallegri F, Pistoia V, Pezzolo A and Palombo D: Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition. PLoS One. 7:e353122012. View Article : Google Scholar : PubMed/NCBI
7	Guzik B, Sagan A, Ludew D, Mrowiecki W, Chwała M, Bujak-Gizycka B, Filip G, Grudzien G, Kapelak B, Zmudka K, et al: Mechanisms of oxidative stress in human aortic aneurysms-association with clinical risk factors for atherosclerosis and disease severity. Int J Cardiol. 168:2389–2396. 2013. View Article : Google Scholar : PubMed/NCBI
8	Kaneko H, Anzai T, Horiuchi K, Kohno T, Nagai T, Anzai A, Takahashi T, Sasaki A, Shimoda M, Maekawa Y, et al: Tumor necrosis factor-α converting enzyme is a key mediator of abdominal aortic aneurysm development. Atherosclerosis. 218:470–478. 2011. View Article : Google Scholar : PubMed/NCBI
9	Sawada H, Hao H, Naito Y, Oboshi M, Hirotani S, Mitsuno M, Miyamoto Y, Hirota S and Masuyama T: Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 35:1507–1514. 2015. View Article : Google Scholar : PubMed/NCBI
10	Gang C, Qiang C, Xiangli C, Shifen P, Chong S and Lihong L: Puerarin suppresses angiotensin ii-induced cardiac hypertrophy by inhibiting nadph oxidase activation and oxidative stress-triggered ap-1 signaling pathways. J Pharm Pharm Sci. 18:235–248. 2015. View Article : Google Scholar : PubMed/NCBI
11	Liu X, Mo Y, Gong J, Li Z, Peng H, Chen J, Wang Q, Ke Z and Xie J: Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Metab Brain Dis. 31:417–423. 2016. View Article : Google Scholar : PubMed/NCBI
12	Gao Z, Wei B and Qian C: Puerarin injection for treatment of unstable angina pectoris: A meta-analysis and systematic review. Int J Clin Exp Med. 8:14577–14594. 2015.PubMed/NCBI
13	Yu Z and Li W: Induction of apoptosis by puerarin in colon cancer HT-29 cells. Cancer Lett. 238:53–60. 2006. View Article : Google Scholar : PubMed/NCBI
14	Kim J, Kim KM, Kim CS, Sohn E, Lee YM, Jo K and Kim JS: Puerarin inhibits the retinal pericyte apoptosis induced by advanced glycation end products in vitro and in vivo by inhibiting NADPH oxidase-related oxidative stress. Free Radic Biol Med. 53:357–365. 2012. View Article : Google Scholar : PubMed/NCBI
15	Ren H, Li F, Tian C, Nie H, Wang L, Li HH and Zheng Y: Inhibition of proteasome activity by low-dose bortezomib attenuates angiotensin ii-induced abdominal aortic aneurysm in apoe(−/-) mice. Sci Rep. 5:157302015. View Article : Google Scholar : PubMed/NCBI
16	Blogowski W, Dolegowska B, Pikula E, Gutowski P and Starzynska T: The effect of PGE administration on the activity of oxidative system in erythrocytes and platelets during ischemia reperfusion injury and on postoperative renal function in patients undergoing open abdominal aortic aneurysm reconstruction. J Biol Regul Homeost Agents. 26:429–438. 2012.PubMed/NCBI
17	Zhang WG, Liu XF, Meng KW and Hu SY: Puerarin inhibits growth and induces apoptosis in SMMC-7721 hepatocellular carcinoma cells. Mol Med Rep. 10:2752–2758. 2014. View Article : Google Scholar : PubMed/NCBI
18	Liu Z, Luo H, Zhang L, Huang Y, Liu B, Ma K, Feng J, Xie J, Zheng J, Hu J, et al: Hyperhomocysteinemia exaggerates adventitial inflammation and angiotensin II-induced abdominal aortic aneurysm in mice. Circ Res. 111:1261–1273. 2012. View Article : Google Scholar : PubMed/NCBI
19	Thomas M, Gavrila D, McCormick ML, Miller FJ Jr, Daugherty A, Cassis LA, Dellsperger KC and Weintraub NL: Deletion of p47phox attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E-deficient mice. Circulation. 114:404–413. 2006. View Article : Google Scholar : PubMed/NCBI
20	Miao XN, Siu KL and Cai H: Nifedipine attenuation of abdominal aortic aneurysm in hypertensive and non-hypertensive mice: Mechanisms and implications. J Mol Cell Cardiol. 87:152–159. 2015. View Article : Google Scholar : PubMed/NCBI
21	Zhang H, Wang ZW, Wu HB, Li Z, Li LC, Hu XP, Ren ZL, Li BJ and Hu ZP: Transforming growth factor-β1 induces matrix metalloproteinase-9 expression in rat vascular smooth muscle cells via ROS-dependent ERK-NF-κB pathways. Mol Cell Biochem. 375:11–21. 2013.PubMed/NCBI
22	Yan H, Cui B, Zhang X, Fu X, Yan J, Wang X, Lv X, Chen Z and Hu Z: Antagonism of toll-like receptor 2 attenuates the formation and progression of abdominal aortic aneurysm. Acta Pharm Sin B. 5:176–187. 2015. View Article : Google Scholar : PubMed/NCBI
23	Zhang J, Guo W, Tian B, Sun M, Li H, Zhou L and Liu X: Puerarin attenuates cognitive dysfunction and oxidative stress in vascular dementia rats induced by chronic ischemia. Int J Clin Exp Pathol. 8:4695–4704. 2015.PubMed/NCBI
24	Dale MA, Suh MK, Zhao S, Meisinger T, Gu L, Swier VJ, Agrawal DK, Greiner TC, Carson JS, Baxter BT and Xiong W: Background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility. Atherosclerosis. 243:621–629. 2015. View Article : Google Scholar : PubMed/NCBI
25	Rabkin SW: Differential expression of MMP-2, MMP-9 and TIMP proteins in thoracic aortic aneurysm - comparison with and without bicuspid aortic valve: a meta-analysis. Vasa. 43:433–442. 2014. View Article : Google Scholar : PubMed/NCBI
26	Zhang T, Xu J, Li D, Chen J, Shen X, Xu F, Teng F, Deng Y, Ma H, Zhang L, et al: Salvianolic acid A, a matrix metalloproteinase-9 inhibitor of Salvia miltiorrhiza, attenuates aortic aneurysm formation in apolipoprotein E-deficient mice. Phytomedicine. 21:1137–1145. 2014. View Article : Google Scholar : PubMed/NCBI
27	Deguchi JO, Huang H, Libby P, Aikawa E, Whittaker P, Sylvan J, Lee RT and Aikawa M: Genetically engineered resistance for MMP collagenases promotes abdominal aortic aneurysm formation in mice infused with angiotensin II. Lab Invest. 89:315–326. 2009. View Article : Google Scholar : PubMed/NCBI
28	Yang X, Zhang H, Wang J, Zhang Z and Li C: Puerarin decreases bone loss and collagen destruction in rats with ligature-induced periodontitis. J Periodontal Res. 50:748–757. 2015. View Article : Google Scholar : PubMed/NCBI
29	Wang C, Chang Q, Qian X, Tian C and Sun X: Angiotensin II induces an increase in MMP-2 expression in idiopathic ascending aortic aneurysm via AT1 receptor and JNK pathway. Acta Biochim Biophys Sin (Shanghai). 47:539–547. 2015. View Article : Google Scholar : PubMed/NCBI
30	DiMusto PD, Lu G, Ghosh A, Roelofs KJ, Sadiq O, McEvoy B, Su G, Laser A, Bhamidipati CM, Ailawadi G, et al: Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm. J Surg Res. 176:687–695. 2012. View Article : Google Scholar : PubMed/NCBI
31	Wang L, Cheng X, Li H, Qiu F, Yang N, Wang B, Lu H, Wu H, Shen Y, Wang Y and Jing H: Quercetin reduces oxidative stress and inhibits activation of cJun Nterminal kinase/activator protein1 signaling in an experimental mouse model of abdominal aortic aneurysm. Mol Med Rep. 9:435–442. 2014. View Article : Google Scholar : PubMed/NCBI