The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway

Scientific Reports

Volumn 7, Issue , 2017, Pages

  Liu, Tong ^a   Zhang, Qinghui ^b   Mo, Wenhui ^c   Yu, Qiang ^d   Xu, Shizan ^d   Li, Jingjing ^a   Li, Sainan ^a   Feng, Jiao ^a   Wu, Liwei ^a   Lu, Xiya ^a   Zhang, Rong ^d   Li, Linqiang ^e   Cheng, Keran ^e   Zhou, Yuqing ^e   Zhou, Shunfeng ^e   Kong, Rui ^e   Wang, Fan ^a   Dai, Weiqi ^a   Chen, Kan ^a   Xia, Yujing ^a   Lu, Jie ^a   Zhou, Yingqun ^a   Zhao, Yan ^a   Guo, Chuanyong ^a   more..

^a TONGJI UNIVERSITY SCHOOL OF MEDICINE   (China)

^b KUNSHAN FIRST PEOPLE S HOSPITAL AFFILIATED TO JIANGSU UNIVERSITY   (China)

^c FUDAN UNIVERSITY   (China)

^d NANJING MEDICAL UNIVERSITY   (China)

^e MEDICAL COLLEGE OF SOOCHOW UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AUTACOID; CYTOKINE; DIMETHYL SULFOXIDE; NAPHTHOQUINONE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTECTIVE AGENT; PROTEIN KINASE B; SHIKONIN;

ANIMAL; APOPTOSIS; AUTOPHAGY; BAGG ALBINO MOUSE; BIOLOGICAL MODEL; DRUG EFFECT; ENZYME ACTIVATION; ENZYMOLOGY; LIVER; LIVER CELL; LIVER FUNCTION TEST; MALE; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; REPERFUSION INJURY; SIGNAL TRANSDUCTION; ULTRASTRUCTURE;

ANIMALS; APOPTOSIS; AUTOPHAGY; CYTOKINES; DIMETHYL SULFOXIDE; ENZYME ACTIVATION; HEPATOCYTES; INFLAMMATION MEDIATORS; LIVER; LIVER FUNCTION TESTS; MALE; MICE, INBRED BALB C; MODELS, BIOLOGICAL; NAPHTHOQUINONES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTECTIVE AGENTS; PROTO-ONCOGENE PROTEINS C-AKT; REPERFUSION INJURY; SIGNAL TRANSDUCTION;

EID: 85016026030     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep44785     Document Type: Article

References (46)

1. Selzner, N., Rudiger, H., Graf, R. & Clavien, P. A. Protective strategies against ischemic injury of the liver. Gastroenterology 125, 917 (2003).
2. Gao, L. et al. Caveolin-1 protects against hepatic ischemia/reperfusion injury through ameliorating peroxynitrite-mediated cell death. Free Radic Biol Med 95, 209 (2016).
3. Karatzas, T., Neri, A. A., Baibaki, M. E. & Dontas, I. A. Rodent models of hepatic ischemia-reperfusion injury: time and percentagerelated pathophysiological mechanisms. J Surg Res 191, 399 (2014).
4. Czubkowski, P., Socha, P. & Pawlowska, J. Oxidative stress in liver transplant recipients. Ann Transplant 16, 99 (2011).
5. Siriussawakul, A., Zaky, A. & Lang, J. D. Role of nitric oxide in hepatic ischemia-reperfusion injury. World J Gastroenterol 16, 6079 (2010).
6. van Golen, R. F., van Gulik, T. M. & Heger, M. The sterile immune response during hepatic ischemia/reperfusion. Cytokine Growth Factor Rev 23, 69 (2012).
7. Zhang, R. et al. Helium preconditioning protects mouse liver against ischemia and reperfusion injury through the PI3K/Akt pathway. J Hepatol 61, 1048 (2014).
8. Fujio, Y., Nguyen, T., Wencker, D., Kitsis, R. N. & Walsh, K. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 101, 660 (2000).
9. Lu, C. et al. The TLR9 ligand, CpG-ODN, induces protection against cerebral ischemia/reperfusion injury via activation of PI3K/Akt signaling. J Am Heart Assoc 3, e629 (2014).
10. Li, J. et al. Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice. Mar Drugs 13, 3368 (2015).
11. Tao, X. et al. Dioscin attenuates hepatic ischemia-reperfusion injury in rats through inhibition of oxidative-nitrative stress, inflammation and apoptosis. Transplantation 98, 604 (2014).
12. Liu, D. et al. Dehydroepiandrosterone protects vascular endothelial cells against apoptosis through a Galphai protein-dependent activation of phosphatidylinositol 3-kinase/Akt and regulation of antiapoptotic Bcl-2 expression. Endocrinology 148, 3068 (2007).
13. Kumar, P., Miller, A. I. & Polverini, P. J. p38 MAPK mediates gamma-irradiation-induced endothelial cell apoptosis, and vascular endothelial growth factor protects endothelial cells through the phosphoinositide 3-kinase-Akt-Bcl-2 pathway. J Biol Chem 279, 43352 (2004).
14. Liu, T. et al. Shikonin Attenuates Concanavalin A-Induced Acute Liver Injury in Mice via Inhibition of the JNK Pathway. Mediators Inflamm 2016, 2748367 (2016).
15. Cheng, P. et al. Hydrogen sulfide ameliorates ischemia/reperfusion-induced hepatitis by inhibiting apoptosis and autophagy pathways. Mediators Inflamm 2014, 935251 (2014).
16. Shen, M. et al. Ethyl pyruvate ameliorates hepatic ischemia-reperfusion injury by inhibiting intrinsic pathway of apoptosis and autophagy. Mediators Inflamm 2013, 461536 (2013).
17. Mao, Y. et al. Ghrelin reduces liver impairment in a model of concanavalin A-induced acute hepatitis in mice. Drug Des Devel Ther 9, 5385 (2015).
18. Li, S. et al. Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3. Drug Des Devel Ther 10, 631 (2016).
19. Li, J. et al. Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis. Plos One 11, e152570 (2016).
20. Ashford, T. P. & Porter, K. R. Cytoplasmic components in hepatic cell lysosomes. J Cell Biol 12, 198 (1962).
21. Zhang, X. et al. Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy 9, 1321 (2013).
22. Kaushal, G. P. Autophagy protects proximal tubular cells from injury and apoptosis. Kidney Int 82, 1250 (2012).
23. Velentzas, P. D. et al. Detrimental effects of proteasome inhibition activity in Drosophila melanogaster: implication of ER stress, autophagy, and apoptosis. Cell Biol Toxicol 29, 13 (2013).
24. Dong, Y., Undyala, V. V., Gottlieb, R. A., Mentzer, R. J. & Przyklenk, K. Autophagy: definition, molecular machinery, and potential role in myocardial ischemia-reperfusion injury. J Cardiovasc Pharmacol Ther 15, 220 (2010).
25. Zhou, X. J. & Zhang, H. Autophagy in immunity: implications in etiology of autoimmune/autoinflammatory diseases. Autophagy 8, 1286 (2012).
26. Cheng, P. et al. Hydrogen sulfide, a potential novel drug, attenuates concanavalin A-induced hepatitis. Drug Des Devel Ther 8, 1277 (2014).
27. Chen, K. et al. 15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy. Biomed Pharmacother 80, 183 (2016).
28. Wang, C. et al. Protective effects of N-acetylcysteine in concanavalin A-induced hepatitis in mice. Mediators Inflamm 2015, 189785 (2015).
29. Li, J. et al. Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis. Plos One 10, e120440 (2015).
30. Wang, R., Yin, R., Zhou, W., Xu, D. & Li, S. Shikonin and its derivatives: a patent review. Expert Opin Ther Pat 22, 977 (2012).
31. Lee, C. C. et al. Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma. Br J Pharmacol 161, 1496 (2010).
32. Liang, W. et al. Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species. Sci Rep 6, 38267 (2016).
33. Wang, Z. et al. Shikonin protects mouse brain against cerebral ischemia/reperfusion injury through its antioxidant activity. Eur J Pharmacol 643, 211 (2010).
34. Wang, L. et al. Protective effect of shikonin in experimental ischemic stroke: attenuated TLR4, p-p38MAPK, NF-kappaB, TNF-alpha and MMP-9 expression, up-regulated claudin-5 expression, ameliorated BBB permeability. Neurochem Res 39, 97 (2014).
35. Zhu, Q., He, G., Wang, J., Wang, Y. & Chen, W. Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice. Sci Rep 6, 22044 (2016).
36. Tao, J., Shen, X., Ai, Y. & Han, X. Tea polyphenols protect against ischemia/reperfusion-induced liver injury in mice through antioxidative and anti-apoptotic properties. Exp Ther Med 12, 3433 (2016).
37. Zhang, Y. et al. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation. Oxid Med Cell Longev 2016, 3919627 (2016).
38. Maddika, S. et al. Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updat 10, 13 (2007).
39. Yu, H. et al. Gypenoside Protects against Myocardial Ischemia-Reperfusion Injury by Inhibiting Cardiomyocytes Apoptosis via Inhibition of CHOP Pathway and Activation of PI3K/Akt Pathway In Vivo and In Vitro. Cell Physiol Biochem 39, 123 (2016).
40. Wu, M. P. et al. Higenamine protects ischemia/reperfusion induced cardiac injury and myocyte apoptosis through activation of beta2-AR/PI3K/AKT signaling pathway. Pharmacol Res 104, 115 (2016).
41. Wang, L. et al. Shikonin protects chondrocytes from interleukin-1beta-induced apoptosis by regulating PI3K/Akt signaling pathway. Int J Clin Exp Pathol 8, 298 (2015).
42. Huang, C. S. et al. Shikonin inhibits oxidized LDL-induced monocyte adhesion by suppressing NFkappaB activation via upregulation of PI3K/Akt/Nrf2-dependent antioxidation in EA. hy926 endothelial cells. Biochem Pharmacol 93, 352 (2015).
43. Zamzami, N. et al. Mitochondrial control of nuclear apoptosis. J Exp Med 183, 1533 (1996).
44. Mukhopadhyay, S., Panda, P. K., Sinha, N., Das, D. N. & Bhutia, S. K. Autophagy and apoptosis: where do they meet? Apoptosis 19 (2014).
45. Qin, H. et al. 15d-prostaglandin J2 protects cortical neurons against oxygen-glucose deprivation/reoxygenation injury: involvement of inhibiting autophagy through upregulation of Bcl-2. Cell Mol Neurobiol 35, 303 (2015).
46. Abe, Y. et al. Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo. Free Radic Biol Med 46, 1 (2009).