Planta Med 2016; 82(03): 181-189
DOI: 10.1055/s-0035-1558114
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Baicalein, a Component of Scutellaria baicalensis, Attenuates Kidney Injury Induced by Myocardial Ischemia and Reperfusion

Chang-Chi Lai
1   Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming University School of Medicine, Taipei, Taiwan
3   Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
,
Po-Hsung Huang
3   Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
4   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
5   Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan
,
An-Han Yang
6   Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
7   Department of Pathology and Laboratory Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
,
Shu-Chiung Chiang
8   Institute of Hospital and Health Care Administration, National Yang-Ming University School of Medicine, Taipei, Taiwan
,
Chia-Yu Tang
1   Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming University School of Medicine, Taipei, Taiwan
3   Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
,
Kuo-Wei Tseng
9   Department of Physical Education and Health, University of Taipei, Taipei, Taiwan
,
Cheng-Hsiung Huang
1   Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Cardiovascular Surgery, Department of Surgery, National Yang-Ming University School of Medicine, Taipei, Taiwan
› Author Affiliations
Further Information

Publication History

received 20 April 2015
revised 09 June 2015

accepted 07 September 2015

Publication Date:
09 November 2015 (online)

Abstract

Acute kidney injury is a common and severe complication of acute myocardial infarction and cardiac surgery. It results in increased mortality, morbidity, and duration of hospitalization. Baicalein is a component of the root of Scutellaria baicalensis, which has traditionally been used to treat cardiovascular and liver diseases in Asia. In this study, we investigated whether baicalein can attenuate kidney injury induced by myocardial ischemia and reperfusion in rats. Myocardial ischemia and reperfusion, induced by a 40-minute occlusion and a 3-hour reperfusion of the left anterior descending coronary artery, significantly increased blood urea nitrogen and creatinine levels in addition to causing histological changes in the kidneys. Kidney apoptosis was also significantly increased. Furthermore, myocardial ischemia and reperfusion significantly increased the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6 as well as the tumor necrosis factor-α levels in the kidneys. Intravenous pretreatment with baicalein (in doses of 3, 10, or 30 mg/kg), however, significantly reduced the increases in the creatinine level, renal histological damage, and apoptosis induced by myocardial ischemia and reperfusion. In addition, the increases in the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6, and of tumor necrosis factor-α in the kidneys were significantly reduced. Western blot analysis revealed that baicalein significantly increased Bcl-2 and reduced Bax in the kidneys. The phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was also significantly increased. In conclusion, baicalein significantly attenuates kidney injury induced by myocardial ischemia and reperfusion. The underlying mechanisms might be related to the inhibition of apoptosis, possibly through the reduction of tumor necrosis factor-α production, the modulation of Bcl-2 and Bax, and the activation of Akt and extracellular signal-regulated kinases 1 and 2.

 
  • References

  • 1 Fox CS, Muntner P, Chen AY, Alexander KP, Roe MT, Wiviot SD. Short-term outcomes of acute myocardial infarction in patients with acute kidney injury: a report from the national cardiovascular data registry. Circulation 2012; 125: 497-504
  • 2 Dardashti A, Ederoth P, Algotsson L, Brondén B, Bjursten H. Incidence, dynamics, and prognostic value of acute kidney injury for death after cardiac surgery. J Thorac Cardiovasc Surg 2014; 147: 800-807
  • 3 Huang CH, Lai CC, Yang AH, Chiang SC. Myocardial preconditioning reduces kidney injury and apoptosis induced by myocardial ischaemia and reperfusion. Eur J Cardiothorac Surg 2015; 48: 382-391
  • 4 Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res 2002; 53: 31-47
  • 5 Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 2001; 11: 372-377
  • 6 Lee HT, Kim JY, Kim M, Wang P, Tang L, Baroni S, DʼAgati VD, Desir GV. Renalase protects against ischemic AKI. J Am Soc Nephrol 2013; 24: 445-455
  • 7 Huang Y, Tsang SY, Yao X, Chen ZY. Biological properties of baicalein in cardiovascular system. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5: 177-184
  • 8 Lee YM, Cheng PY, Chim LS, Kung CW, Ka SM, Chung MT, Sheu JR. Baicalein, an active component of Scutellaria baicalensis Georgi, improves cardiac contractile function in endotoxaemic rats via induction of heme oxygenase-1 and suppression of inflammatory responses. J Ethnopharmacol 2011; 135: 179-185
  • 9 Sun H, Che QM, Zhao X, Pu XP. Antifibrotic effects of chronic baicalein administration in a CCl4 liver fibrosis model in rats. Eur J Pharmacol 2010; 631: 53-60
  • 10 Jo SK, Rosner MH, Okusa MD. Pharmacologic treatment of acute kidney injury: why drugs havenʼt worked and what is on the horizon. Clin J Am Soc Nephrol 2007; 2: 356-365
  • 11 Lee EK, Kim JM, Choi J, Jung KJ, Kim DH, Chung SW, Ha YM, Yu BP, Chung HY. Modulation of NF-κB and FOXOs by baicalein attenuates the radiation-induced inflammatory process in mouse kidney. Free Radic Res 2011; 45: 507-517
  • 12 Ahad A, Mujeeb M, Ahsan H, Siddiqui WA. Prophylactic effect of baicalein against renal dysfunction in type 2 diabetic rats. Biochimie 2014; 106: 101-110
  • 13 Chen HM, Hsu JH, Liou SF, Chen TJ, Chen LY, Chiu CC, Yeh JL. Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways. BMC Complement Altern Med 2014; 14: 233
  • 14 Huang HH, Shao ZH, Li CQ, Vanden Hoek TL, Li J. Baicalein protects cardiomyocytes against mitochondrial oxidant injury associated with JNK inhibition and mitochondrial Akt activation. Am J Chin Med 2014; 42: 79-94
  • 15 Venugopal V, Laing CM, Ludman A, Yellon DM, Hausenloy D. Effect of remote ischemic preconditioning on acute kidney injury in nondiabetic patients undergoing coronary artery bypass graft surgery: a secondary analysis of 2 small randomized trials. Am J Kidney Dis 2010; 56: 1043-1049
  • 16 Lin M, Li L, Li L, Pokhrel G, Qi G, Rong R, Zhu T. The protective effect of baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis. BMC Complement Altern Med 2014; 14: 19
  • 17 Huang HH, Lai CC, Chiang SC, Chang SC, Chang CH, Lin JC, Huang CH. Brief left ventricular pressure overload reduces myocardial apoptosis. J Surg Res 2015; 194: 34-42
  • 18 Zhang L, Shao X, Zhou C, Guo X, Jin L, Lian L, Yu X, Dong Z, Mo Y, Fang J. Transcutaneous electrical nerve stimulation regulates organ blood flow and apoptosis during controlled hypotension in dogs. PLoS One 2014; 9: e94368
  • 19 Huang CH, Tsai SK, Chiang SC, Wang YY, Chih CL, Weng ZC, Lai ST. Brief pressure overload preconditions rabbit myocardium independent of adenosine receptor activation. Ann Thorac Surg 2011; 92: 1727-1732
  • 20 Gulmen S, Kiris I, Narin C, Ceylan BG, Mermi B, Sutcu R, Meteoglu I. Tezosentan reduces the renal injury induced by abdominal aortic ischemia-reperfusion in rats. J Surg Res 2009; 157: e7-e13