Oleanolic acid alleviates diabetic rat carotid artery injury through the inhibition of NLRP3 inflammasome signaling pathways

An,Qian; Hu,Qian; Wang,Bing; Cui,Wenjun; Wu,Fei; Ding,Yu

doi:10.3892/mmr.2017.7594

Oleanolic acid alleviates diabetic rat carotid artery injury through the inhibition of NLRP3 inflammasome signaling pathways

Authors:
- Qian An
- Qian Hu
- Bing Wang
- Wenjun Cui
- Fei Wu
- Yu Ding
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Affiliations: Department of Vascular Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 470000, P.R. China, Staff Room of Surgery, Zhengzhou Railway Vocational Technical College, Zhengzhou, Henan 450052, P.R. China
Published online on: September 25, 2017 https://doi.org/10.3892/mmr.2017.7594
Pages: 8413-8419

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Abstract

The overexpression of inflammasome components is correlated with diabetes‑associated complications. Oleanolic acid is a triterpenoid compound which is important in arterial injury. The present study evaluated whether oleanolic acid improved diabetic rat carotid artery injury through the inhibition of nucleotide‑binding domain, leucine‑rich‑containing family, pyrin domain‑containing‑3 (NLRP3) inflammasomes signaling pathways. A diabetic rat model was induced using streptozotocin (60 mg/kg) and underwent carotid artery injury. Morphometric analysis was performed using hematoxylin and eosin staining. The mRNA and protein levels were assayed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. It was found that oleanolic acid (100 mg/kg/day) improved body weight, glucose metabolic disorders, neointimal hyperplasia and endothelial dysfunction in diabetic rats with carotid artery injury. In addition, oleanolic acid administration significantly downregulated the mRNA and protein expression levels of endothelin 1 in diabetic rats. Oleanolic acid decreased the intimal area and the ratio of neointima to media in diabetic rats. Serum levels of tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and IL‑18 in the oleanolic acid‑treated diabetic rats were downregulated. Consistent with the serum results, it was demonstrated that oleanolic acid administration caused a significant decrease in the levels of NLRP3, caspase‑1 and IL‑1β in the carotid arteries of diabetic rats. Taken together, these observations suggested that oleanolic acid attenuated carotid artery injury in diabetic rats and the underlying mechanism was mediated, at least partially, through the suppression of NLRP3 inflammasome signaling pathways.

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1	Irie Y, Katakami N, Kaneto H, Kasami R, Sumitsuji S, Yamasaki K, Tachibana K, Kuroda T, Sakamoto K, Umayahara Y, et al: Maximum carotid intima-media thickness improves the prediction ability of coronary artery stenosis in type 2 diabetic patients without history of coronary artery disease. Atherosclerosis. 221:438–444. 2012. View Article : Google Scholar : PubMed/NCBI
2	Tian F, Chen Y, Liu H, Zhang T, Guo J and Jin Q: Assessment of characteristics of neointimal hyperplasia after drug-eluting stent implantation in patients with diabetes mellitus: An optical coherence tomography analysis. Cardiology. 128:34–40. 2014. View Article : Google Scholar : PubMed/NCBI
3	Yang J, Fan Z, Yang J, Ding J, Yang C and Chen L: MicroRNA-24 attenuates neointimal hyperplasia in the diabetic rat carotid artery injury model by inhibiting Wnt4 signaling pathway. Int J Mol Sci. 17:E7652016. View Article : Google Scholar : PubMed/NCBI
4	Wang K, Zhou Z, Zhang M, Fan L, Forudi F, Zhou X, Qu W, Lincoff AM, Schmidt AM, Topol EJ and Penn MS: Peroxisome proliferator-activated receptor gamma down-regulates receptor for advanced glycation end products and inhibits smooth muscle cell proliferation in a diabetic and nondiabetic rat carotid artery injury model. J Pharmacol Exp Ther. 317:37–43. 2006. View Article : Google Scholar : PubMed/NCBI
5	Simon DI: Inflammation and vascular injury: Basic discovery to drug development. Circ J. 76:1811–1818. 2012. View Article : Google Scholar : PubMed/NCBI
6	Sirico G, Spadera L, De Laurentis M and Brevetti G: Carotid artery disease and stroke in patients with peripheral arterial disease. The role of inflammation. Monaldi Arch Chest Dis. 72:10–17. 2009.PubMed/NCBI
7	Xia M, Boini KM, Abais JM, Xu M, Zhang Y and Li PL: Endothelial NLRP3 inflammasome activation and enhanced neointima formation in mice by adipokine visfatin. Am J Pathol. 184:1617–1628. 2014. View Article : Google Scholar : PubMed/NCBI
8	Shi X, Xie WL, Kong WW, Chen D and Qu P: Expression of the NLRP3 Inflammasome in Carotid Atherosclerosis. J Stroke Cerebrovasc Dis. 24:2455–2466. 2015. View Article : Google Scholar : PubMed/NCBI
9	Zheng F, Xing S, Gong Z and Xing Q: NLRP3 inflammasomes show high expression in aorta of patients with atherosclerosis. Heart Lung Circ. 22:746–750. 2013. View Article : Google Scholar : PubMed/NCBI
10	Goyal SN, Mahajan UB, Chandrayan G, Kumawat VS, Kamble S, Patil P, Agrawal YO, Patil CR and Ojha S: Protective effect of oleanolic acid on oxidative injury and cellular abnormalities in doxorubicin induced cardiac toxicity in rats. Am J Transl Res. 8:60–69. 2016.PubMed/NCBI
11	Madlala HP, Van Heerden FR, Mubagwa K and Musabayane CT: Changes in renal function and oxidative status associated with the hypotensive effects of oleanolic acid and related synthetic derivatives in experimental animals. PLoS One. 10:e01281922015. View Article : Google Scholar : PubMed/NCBI
12	Yu Z, Sun W, Peng W, Yu R, Li G and Jiang T: Pharmacokinetics in vitro and in vivo of two novel prodrugs of oleanolic acid in rats and its hepatoprotective effects against liver injury induced by CCl4. Mol Pharm. 13:1699–1710. 2016. View Article : Google Scholar : PubMed/NCBI
13	Liese J, Abhari BA and Fulda S: Smac mimetic and oleanolic acid synergize to induce cell death in human hepatocellular carcinoma cells. Cancer Lett. 365:47–56. 2015. View Article : Google Scholar : PubMed/NCBI
14	Wang X, Chen Y, Abdelkader D and Hassan W: Combination therapy with oleanolic acid and metformin as a synergistic treatment for diabetes. J Diabetes Res. 2015:9732872015. View Article : Google Scholar : PubMed/NCBI
15	Camer D, Yu Y, Szabo A and Huang XF: The molecular mechanisms underpinning the therapeutic properties of oleanolic acid, its isomer and derivatives for type 2 diabetes and associated complications. Mol Nutr Food Res. 58:1750–1759. 2014. View Article : Google Scholar : PubMed/NCBI
16	Lu J, Wu DM, Zheng YL, Hu B, Cheng W, Zhang ZF and Shan Q: Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IkappaB kinase beta/nuclear factor-κB-mediated inflammatory pathways in mice. Brain Behav Immun. 25:1658–1667. 2011. View Article : Google Scholar : PubMed/NCBI
17	Buus NH, Hansson NC, Rodriguez-Rodriguez R, Stankevicius E, Andersen MR and Simonsen U: Antiatherogenic effects of oleanolic acid in apolipoprotein E knockout mice. Eur J Pharmacol. 670:519–526. 2011. View Article : Google Scholar : PubMed/NCBI
18	Zheng Z, Chen H, Wang H, Ke B, Zheng B, Li Q, Li P, Su L, Gu Q and Xu X: Improvement of retinal vascular injury in diabetic rats by statins is associated with the inhibition of mitochondrial reactive oxygen species pathway mediated by peroxisome proliferator-activated receptor gamma coactivator 1alpha. Diabetes. 59:2315–2325. 2010. View Article : Google Scholar : PubMed/NCBI
19	Chai J, He Y, Cai SY, Jiang Z, Wang H, Li Q, Chen L, Peng Z, He X, Wu X, et al: Elevated hepatic multidrug resistance-associated protein 3/ATP-binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c-Jun NH2-terminal kinase/stress-activated protein kinase-signaling pathway. Hepatology. 55:1485–1494. 2012. View Article : Google Scholar : PubMed/NCBI
20	Dushpanova A, Agostini S, Ciofini E, Cabiati M, Casieri V, Matteucci M, Del Ry S, Clerico A, Berti S and Lionetti V: Gene silencing of endothelial von Willebrand factor attenuates angiotensin II-induced endothelin-1 expression in porcine aortic endothelial cells. Sci Rep. 6:300482016. View Article : Google Scholar : PubMed/NCBI
21	Tousoulis D, Kampoli AM, Tentolouris C, Papageorgiou N and Stefanadis C: The role of nitric oxide on endothelial function. Curr Vasc Pharmacol. 10:4–18. 2012. View Article : Google Scholar : PubMed/NCBI
22	Wong BW, Wong D, Luo H and McManus BM: Vascular endothelial growth factor-D is overexpressed in human cardiac allograft vasculopathy and diabetic atherosclerosis and induces endothelial permeability to low-density lipoproteins in vitro. J Heart Lung Transplant. 30:955–962. 2011.PubMed/NCBI
23	Satoh M, Tabuchi T, Itoh T and Nakamura M: NLRP3 inflammasome activation in coronary artery disease: Results from prospective and randomized study of treatment with atorvastatin or rosuvastatin. Clin Sci (Lond). 126:233–241. 2014. View Article : Google Scholar : PubMed/NCBI
24	Saita D, Ferrarese R, Foglieni C, Esposito A, Canu T, Perani L, Ceresola ER, Visconti L, Burioni R, Clementi M and Canducci F: Adaptive immunity against gut microbiota enhances apoE-mediated immune regulation and reduces atherosclerosis and western-diet-related inflammation. Sci Rep. 6:293532016. View Article : Google Scholar : PubMed/NCBI
25	Chow BS, Koulis C, Krishnaswamy P, Steckelings UM, Unger T, Cooper ME, Jandeleit-Dahm KA and Allen TJ: The angiotensin II type 2 receptor agonist compound 21 is protective in experimental diabetes-associated atherosclerosis. Diabetologia. 59:1778–1790. 2016. View Article : Google Scholar : PubMed/NCBI
26	Kirii H, Niwa T, Yamada Y, Wada H, Saito K, Iwakura Y, Asano M, Moriwaki H and Seishima M: Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 23:656–660. 2003. View Article : Google Scholar : PubMed/NCBI
27	Mallat Z, Corbaz A, Scoazec A, Graber P, Alouani S, Esposito B, Humbert Y, Chvatchko Y and Tedgui A: Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability. Circ Res. 89:E41–E45. 2001. View Article : Google Scholar : PubMed/NCBI
28	Gage J, Hasu M, Thabet M and Whitman SC: Caspase-1 deficiency decreases atherosclerosis in apolipoprotein E-null mice. Can J Cardiol. 28:222–229. 2012. View Article : Google Scholar : PubMed/NCBI
29	Gao D, Li Q, Li Y, Liu Z, Fan Y, Liu Z, Zhao H, Li J and Han Z: Antidiabetic and antioxidant effects of oleanolic acid from Ligustrum lucidum Ait in alloxan-induced diabetic rats. Phytother Res. 23:1257–1262. 2009. View Article : Google Scholar : PubMed/NCBI
30	Osborn O and Olefsky JM: The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 18:363–374. 2012. View Article : Google Scholar : PubMed/NCBI