Open Access

Curcumin‑loaded PEG‑PDLLA nanoparticles for attenuating palmitate‑induced oxidative stress and cardiomyocyte apoptosis through AMPK pathway

  • Authors:
    • Jingyi Zhang
    • Ying Wang
    • Cuiyu Bao
    • Tao Liu
    • Shuai Li
    • Jiaxi Huang
    • Ying Wan
    • Jing Li
  • View Affiliations

  • Published online on: June 5, 2019     https://doi.org/10.3892/ijmm.2019.4228
  • Pages: 672-682
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Curcumin (CUR) has the ability to attenuate oxidative stress in the myocardium and to protect the myocardium from lipotoxic injury owing to its lipid‑reducing properties. However, the use of CUR is limited due to its hydrophobicity and instability. In this study, CUR‑loaded nanoparticles (CUR NPs) were developed using an amphiphilic copolymer, monomethoxy poly (ethylene glycol)‑b‑poly (DL‑lactide), as a vehicle material. CUR NPs with high drug loading and small size were prepared under optimized conditions. The effects of CUR NPs on palmitate‑induced cardiomyocyte injury were investigated and the possible protective mechanism of CUR NPs was also examined. It was found that CUR NPs were able to control the release of CUR and to deliver CUR to H9C2 cells, and they could prevent palmitate‑treated H9C2 cells from apoptosis. In addition, CUR NPs could regulate the Bax and Bcl‑2 levels of palmitate‑treated H9C2 cells back to their respective normal levels. A prospective mechanism for the function of CUR NPs is that they may activate the AMP‑activated protein kinase (AMPK)/mammalian target of rapamycin complex‑1/p‑p70 ribosomal protein S6 kinase signaling pathway, regulate the expression of downstream proteins and resist the palmitate‑induced cardiomyocyte injury. Results suggest that CUR NPs can attenuate palmitate‑induced oxidative stress in cardiomyocytes and protect cardiomyocytes from apoptosis through the AMPK pathway. In view of the safety and efficiency of these CUR NPs, they have potential for application in protecting the myocardium from lipotoxic injury.

References

1 

Kim J, Joo S, Eom GH, Lee SH, Lee MA, Lee M, Kim KW, Kim DH, Kook H, Kwak TH and Park WJ: CCN5 knockout mice exhibit lipotoxic cardiomyopathy with mild obesity and diabetes. PLoS One. 13:e02072282018. View Article : Google Scholar : PubMed/NCBI

2 

Pulinilkunnil T, Kienesberger PC, Nagendran J, Waller TJ, Young ME, Kershaw EE, Korbutt G, Haemmerle G, Zechner R and Dyck JR: Myocardial adipose triglyceride lipase overexpression protects diabetic mice from the development of lipotoxic cardiomyopathy. Diabetes. 62:1464–1477. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Jeong MH, Tran NK, Kwak TH, Park BK, Lee CS, Park TS, Lee YH, Park WJ and Yang DK: β-Lapachone ameliorates lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice. PLoS One. 9:e910392014. View Article : Google Scholar

4 

Walls SM, Cammarato A, Chatfield DA, Ocorr K, Harris GL and Bodmer R: Ceramide-protein interactions modulate ceramide-associated lipotoxic cardiomyopathy. Cell Rep. 22:2702–2715. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Drosatos K and Schulze PC: Cardiac lipotoxicity: Molecular pathways and therapeutic implications. Curr Heart Fail Rep. 10:109–121. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Law BA, Liao X, Moore KS, Southard A, Roddy P, Ji R, Szulc Z, Bielawska A, Schulze PC and Cowart LA: Lipotoxic very-long-chain ceramides cause mitochondrial dysfunction, oxidative stress, and cell death in cardiomyocytes. FASEB J. 32:1403–1416. 2018. View Article : Google Scholar :

7 

Pillutla P, Hwang YC, Augustus A, Yokoyama M, Yagyu H, Johnston TP, Kaneko M, Ramasamy R and Goldberg IJ: Perfusion of hearts with triglyceride-rich particles reproduces the metabolic abnormalities in lipotoxic cardiomyopathy. Am J Physiol Endocrinol Metab. 288:E1229–E1235. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Malfitano C, de Souza Junior AL, Carbonaro M, Bolsoni-Lopes A, Figueroa D, de Souza LE, Silva KA, Consolim-Colombo F, Curi R and Irigoyen MC: Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling. Cardiovasc Diabetol. 14:1492015. View Article : Google Scholar

9 

Carpentier AC: Abnormal myocardial dietary fatty acid metabolism and diabetic cardiomyopathy. Can J Cardiol. 34:605–614. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Mangolim AS, Brito LAR and Nunes-Nogueira VS: Effectiveness of testosterone therapy in obese men with low testosterone levels, for losing weight, controlling obesity complications, and preventing cardiovascular events: Protocol of a systematic review of randomized controlled trials. Medicine (Baltimore). 97:e04822018. View Article : Google Scholar

11 

Son NH, Yu S, Tuinei J, Arai K, Hamai H, Homma S, Shulman GI, Abel ED and Goldberg IJ: PPARγ-induced cardiolipotoxicity in mice is ameliorated by PPARα deficiency despite increases in fatty acid oxidation. J Clin Invest. 120:3443–3454. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Mita Y, et al: p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation. Circ Heart Fail. 5:106–115. 2012. View Article : Google Scholar

13 

Finck BN, Han X, Courtois M, Aimond F, Nerbonne JM, Kovacs A, Gross RW and Kelly DP: A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation by dietary fat content. Proc Natl Acad Sci USA. 100:1226–1231. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Britto RM, Silva-Neto JAD, Mesquita TRR, Vasconcelos CML, de Almeida GKM, Jesus ICG, Santos PHD, Souza DS, Miguel-Dos-Santos R, de Sá LA, et al: Myrtenol protects against myocardial ischemia-reperfusion injury through antioxidant and anti-apoptotic dependent mechanisms. Food Chem Toxicol. 111:557–566. 2018. View Article : Google Scholar

15 

Guo S, Yao Q, Ke Z, Chen H, Wu J and Liu C: Resveratrol attenuates high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK. Mol Cell Endocrinol. 412:85–94. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Lu CW, Hao JL, Yao L, Li HJ and Zhou DD: Efficacy of curcumin in inducing apoptosis and inhibiting the expression of VEGF in human pterygium fibroblasts. Int J Mol Med. 39:1149–1154. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Mujtaba T, Kanwar J, Wan SB, Chan TH and Dou QP: Sensitizing human multiple myeloma cells to the proteasome inhibitor bortezomib by novel curcumin analogs. Int J Mol Med. 29:102–106. 2012.

18 

Chen Z, Xue J, Shen T, Mu S and Fu Q: Curcumin alleviates glucocorticoid-induced osteoporosis through the regulation of the Wnt signaling pathway. Int J Mol Med. 37:329–338. 2016. View Article : Google Scholar :

19 

Mohajeri M and Sahebkar A: Protective effects of curcumin against doxorubicin-induced toxicity and resistance: A review. Crit Rev Oncol Hematol. 122:30–51. 2018. View Article : Google Scholar : PubMed/NCBI

20 

Santezi C, Reina BD and Dovigo LN: Curcumin-mediated photo-dynamic therapy for the treatment of oral infections-a review. Photodiagnosis Photodyn Ther. 21:409–415. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Hosseini A and Hosseinzadeh H: Antidotal or protective effects of curcuma longa (turmeric) and its active ingredient, curcumin, against natural and chemical toxicities: A review. Biomed Pharmacother. 99:411–421. 2018. View Article : Google Scholar : PubMed/NCBI

22 

Gawde KA, Sau S, Tatiparti K, Kashaw SK, Mehrmohammadi M, Azmi AS and Iyer AK: Paclitaxel and di-fluorinated curcumin loaded in albumin nanoparticles for targeted synergistic combination therapy of ovarian and cervical cancers. Colloid Surf B Biointerfaces. 167:8–19. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Jiang S, Han J, Li T, Xin Z, Ma Z, Di W, Hu W, Gong B, Di S, Wang D and Yang Y: Curcumin as a potential protective compound against cardiac diseases. Pharmacol Res. 119:373–383. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Zhao G, Liu Y, Yi X, Wang Y, Qiao S, Li Z, Ni J and Song Z: Curcumin inhibiting Th17 cell differentiation by regulating the metabotropic glutamate receptor-4 expression on dendritic cells. Int Immunopharmacol. 46:80–86. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Qi Z, Wu M, Fu Y, Huang T, Wang T, Sun Y, Feng Z and Li C: Palmitic acid curcumin ester facilitates protection of neuroblastoma against oligomeric aβ40 insult. Cell Physiol Biochem. 44:618–633. 2017. View Article : Google Scholar

26 

Ren J and Sowers JR: Application of a novel curcumin analog in the management of diabetic cardiomyopathy. Diabetes. 63:3166–3168. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Li K, Liu Y, Zhang S, Xu Y, Jiang J, Yin F, Hu Y, Han B, Ge S, Zhang L and Wang Y: Folate receptor-targeted ultrasonic PFOB nanoparticles: Synthesis, characterization and application in tumor-targeted imaging. Int J Mol Med. 39:1505–1515. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Jiang X, Zhong Y, Zheng L and Zhao J: Nano-hydroxyapatite/collagen film as a favorable substrate to maintain the phenotype and promote the growth of chondrocytes cultured in vitro. Int J Mol Med. 41:2150–2158. 2018.PubMed/NCBI

29 

Jiang C, Wang H, Zhang X, Sun Z, Wang F, Cheng J, Xie H, Yu B and Zhou L: Deoxycholic acid-modified chitooligosaccharide/mPEG-PDLLA mixed micelles loaded with paclitaxel for enhanced antitumor efficacy. Int J Pharm. 475:60–68. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Chen Q, Pang MH, Ye XH, Yang G and Lin C: The toxoplasma gondii ME-49 strain upregulates levels of A20 that inhibit NF-κB activation and promotes apoptosis in human leukaemia T-cell lines. Parasite Vector. 11:3052018. View Article : Google Scholar

31 

Shiomi M, Ishida T, Kobayashi T, Nitta N, Sonoda A, Yamada S, Koike T, Kuniyoshi N, Murata K, Hirata K, et al: Vasospasm of atherosclerotic coronary arteries precipitates acute ischemic myocardial damage in myocardial infarction-prone strain of the watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol. 33:2518–2523. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Li TB, Zhang YZ, Liu WQ, Zhang JJ, Peng J, Luo XJ and Ma QL: Correlation between NADPH oxidase-mediated oxidative stress and dysfunction of endothelial progenitor cell in hyperlipidemic patients. Korean J Intern Med. 33:313–322. 2018. View Article : Google Scholar :

33 

Yang SM, Liu J and Li CX: Intermedin protects against myocardial ischemia-reperfusion injury in hyperlipidemia rats. Genet Mol Res. 13:8309–8319. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Vendrov AE, Vendrov KC, Smith A, Yuan J, Sumida A, Robidoux J, Runge MS and Madamanchi NR: NOX4 NADPH oxidase-dependent mitochondrial oxidative stress in aging-associated cardiovascular disease. Antioxid Redox Signal. 23:1389–1409. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Lucas ML, Carraro CC, Bello-Klein A, Kalil AN, Aerts NR, Carvalho FB, Fernandes MC and Zettler CG: Oxidative stress in aortas of patients with advanced occlusive and aneurysmal diseases. Ann Vasc Surg. 52:216–224. 2018. View Article : Google Scholar : PubMed/NCBI

36 

Murugesu K, Murugaiyah V, Saghir SAM, Asmawi MZ and Sadikun A: Caffeoylquinic acids rich versus poor fractions of gynura procumbens: Their comparative antihyperlipidemic and antioxidant potential. Curr Pharm Biotechnol. 18:1132–1140. 2017. View Article : Google Scholar

37 

Hadzi-Petrushev N, Bogdanov J, Krajoska J, Ilievska J, Bogdanova-Popov B, Gjorgievska E, Mitrokhin V, Sopi R, Gagov H, Kamkin A and Mladenov M: Comparative study of the antioxidant properties of monocarbonyl curcumin analogues C66 and B2BrBC in isoproteranol induced cardiac damage. Life Sci. 197:10–18. 2018. View Article : Google Scholar : PubMed/NCBI

38 

Li TB, Zhang JJ, Liu B, Luo XJ, Ma QL and Peng J: Dysfunction of endothelial progenitor cells in hyperlipidemic rats involves the increase of NADPH oxidase derived reactive oxygen species production. Can J Physiol Pharmacol. 95:474–480. 2017. View Article : Google Scholar : PubMed/NCBI

39 

Lei S, Sun RZ, Wang D, Gong MZ, Su XP, Yi F and Peng ZW: Increased hepatic fatty acids uptake and oxidation by LRPPRC-driven oxidative phosphorylation reduces blood lipid levels. Front Physiol. 7:2702016. View Article : Google Scholar : PubMed/NCBI

40 

Fan HC, Fernandez-Hernando C and Lai JH: Protein kinase C isoforms in atherosclerosis: Pro- or anti-inflammatory? Biochem Pharmacol. 88:139–149. 2014. View Article : Google Scholar : PubMed/NCBI

41 

Chiu CJ and Taylor A: Dietary hyperglycemia, glycemic index and metabolic retinal diseases. Prog Retin Eye Res. 30:18–53. 2011. View Article : Google Scholar

42 

Yang R, Chu X, Sun L, Kang Z, Ji M, Yu Y, Liu Y, He Z and Gao N: Hypolipidemic activity and mechanisms of the total phenylpropanoid glycosides from ligustrum robustum (Roxb.) Blume by AMPK-SREBP-1c pathway in hamsters fed a high-fat diet. Phytother Res. 32:715–722. 2018. View Article : Google Scholar : PubMed/NCBI

43 

Lin CH, Kuo YH and Shih CC: Effects of bofutsusho-san on diabetes and hyperlipidemia associated with AMP-activated protein kinase and glucosetransporter 4 in high-fat-fed mice. Int J Mol Sci. 15:20022–20044. 2014. View Article : Google Scholar : PubMed/NCBI

44 

Vinayagam R, Jayachandran M, Chung SSM and Xu B: Guava leaf inhibits hepatic gluconeogenesis and increases glycogen synthesis via AMPK/ACC signaling pathways in streptozotocin-induced diabetic rats. Biomed Pharmacother. 103:1012–1017. 2018. View Article : Google Scholar : PubMed/NCBI

45 

Yeung PK, Kolathuru SS, Mohammadizadeh S, Akhoundi F and Linderfield B: Adenosine 5′-triphosphate metabolism in red blood cells as a potential biomarker for post-exercise hypotension and a drug target for cardiovascular protection. Metabolites. 8:E302018. View Article : Google Scholar

46 

Mollica MP, Mattace Raso G, Cavaliere G, Trinchese G, De Filippo C, Aceto S, Prisco M, Pirozzi C, Di Guida F, Lama A, et al: Butyrate regulates liver mitochondrial function, efficiency, and dynamics in insulin-resistant obese mice. Diabetes. 66:1405–1418. 2017. View Article : Google Scholar : PubMed/NCBI

47 

Li Y, Zhou ZH, Chen MH, Yang J, Leng J, Cao GS, Xin GZ, Liu LF, Kou JP, Liu BL, et al: Inhibition of mitochondrial fission and NOX2 expression prevent NLRP3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction. Antioxid Redox Signal. 24:893–908. 2016. View Article : Google Scholar : PubMed/NCBI

48 

Lone J, Choi JH, Kim SW and Yun JW: Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes. J Nutr Biochem. 27:193–202. 2016. View Article : Google Scholar

49 

Pu Y, Zhang H, Wang P, Zhao Y, Li Q, Wei X, Cui Y, Sun J, Shang Q, Liu D and Zhu Z: Dietary curcumin ameliorates aging-related cerebrovascular dysfunction through the AMPK/uncoupling protein 2 pathway. Cell Physiol Biochem. 32:1167–1177. 2013. View Article : Google Scholar : PubMed/NCBI

50 

Yang K, Xu C, Li X and Jiang H: Combination of D942 with curcumin protects cardiomyocytes from ischemic damage through promoting autophagy. J Cardiovasc Pharmacol Ther. 18:570–581. 2013. View Article : Google Scholar : PubMed/NCBI

51 

Mikhailov V, Mikhailova M, Pulkrabek DJ, Dong Z, Venkatachalam MA and Saikumar P: Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J Biol Chem. 276:18361–18374. 2001. View Article : Google Scholar : PubMed/NCBI

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August 2019
Volume 44 Issue 2

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Copy and paste a formatted citation
APA
Zhang, J., Wang, Y., Bao, C., Liu, T., Li, S., Huang, J. ... Li, J. (2019). Curcumin‑loaded PEG‑PDLLA nanoparticles for attenuating palmitate‑induced oxidative stress and cardiomyocyte apoptosis through AMPK pathway. International Journal of Molecular Medicine, 44, 672-682. https://doi.org/10.3892/ijmm.2019.4228
MLA
Zhang, J., Wang, Y., Bao, C., Liu, T., Li, S., Huang, J., Wan, Y., Li, J."Curcumin‑loaded PEG‑PDLLA nanoparticles for attenuating palmitate‑induced oxidative stress and cardiomyocyte apoptosis through AMPK pathway". International Journal of Molecular Medicine 44.2 (2019): 672-682.
Chicago
Zhang, J., Wang, Y., Bao, C., Liu, T., Li, S., Huang, J., Wan, Y., Li, J."Curcumin‑loaded PEG‑PDLLA nanoparticles for attenuating palmitate‑induced oxidative stress and cardiomyocyte apoptosis through AMPK pathway". International Journal of Molecular Medicine 44, no. 2 (2019): 672-682. https://doi.org/10.3892/ijmm.2019.4228