Skip to main content
SpringerLink
Log in

Neuroprotective Effect of Baicalin in a Rat Model of Permanent Focal Cerebral Ischemia

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

This investigation was performed to determine the neuroprotective effect of baicalin on permanent cerebral ischemia injury in rats and the potential mechanisms in this process. Adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). The rats were then received intraperitoneal injection with baicalin (10, 30 and 100 mg/kg) or vehicle. Morphological characteristic, neurological deficit scores, cerebral infarct volume and the enzymatic activity of myeloperoxidase (MPO) were measured 24 h after pMCAO. The mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by RT-PCR. Neuronal apoptosis was determined by TUNEL staining and Western blot. Baicalin (30 and 100 mg/kg) reduced neurological deficit scores and cerebral infarct volume 24 h after pMCAO. Baicalin significantly decreased the enzymatic activity of MPO and the expression of iNOS mRNA and COX-2 mRNA in rat brain, it also significantly inhibited neuronal apoptosis and the expression of cleaved caspase-3 protein after pMCAO. Our results suggested that baicalin possesses potent anti-inflammatory and anti-apoptotic properties and attenuates cerebral ischemia injury. This protection might be associated with the downregulated expression of iNOS mRNA, COX-2 mRNA, and cleaved caspase-3 protein.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Durukan A, Tatlisumak T (2007) Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia. Pharmacol Biochem Behav 87:179–197. doi:10.1016/j.pbb.2007.04.015

    Article  PubMed  CAS  Google Scholar 

  2. Lapchak PA, Araujo DM (2007) Advances in ischemic stroke treatment: neuroprotective and combination therapies. Expert Opin Emerg Drugs 12:97–112. doi:10.1517/14728214.12.1.97

    Article  PubMed  CAS  Google Scholar 

  3. Nagahiro S, Uno M, Sato K et al (1998) Pathophysiology and treatment of cerebral ischemia. J Med Invest 45:57–70

    PubMed  CAS  Google Scholar 

  4. Iadecola C, Zhang F, Casey R et al (1997) Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the iNOS gene. J Neurosci 17:9157–9164

    PubMed  CAS  Google Scholar 

  5. Nogawa S, Zhang F, Ross ME et al (1997) Cyclo-oxygenase-2 gene expression in neurons contributes to ischemic brain damage. J Neurosci 17:2746–2755

    PubMed  CAS  Google Scholar 

  6. Nogawa S, Forster C, Zhang F et al (1998) Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia. Proc Natl Acad Sci USA 95:10966–10971. doi:10.1073/pnas.95.18.10966

    Article  PubMed  CAS  Google Scholar 

  7. Iadecola C, Zhang F, Xu X (1995) Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage. Am J Physiol Regul Integr Comp Physiol 268:286–292

    Google Scholar 

  8. Candelario-Jalil E, González-Falcón A, García-Cabrera M et al (2004) Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat. Brain Res 1007:98–108. doi:10.1016/j.brainres.2004.01.078

    Article  PubMed  CAS  Google Scholar 

  9. Chop M, Li Y, Jiang N et al (1996) Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. J Cereb Blood Flow Metab 16:578–584. doi:10.1097/00004647-199607000-00007

    Article  Google Scholar 

  10. Hwang JM, Wang CJ, Chou FP et al (2005) Protective effect of baicalin on tert-butyl hydroperoxide-induced rat hepatotoxicity. Arch Toxicol 79:102–109. doi:10.1007/s00204-004-0588-6

    Article  PubMed  CAS  Google Scholar 

  11. Li BQ, Fu T, Gong WH et al (2000) The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines. Immunopharmacology 49:295–306. doi:10.1016/S0162-3109(00)00244-7

    Article  PubMed  CAS  Google Scholar 

  12. Jung SH, Kang KD, Ji D et al (2008) The flavonoid baicalin counteracts ischemic and oxidative insults to retinal cells and lipid peroxidation to brain membranes. Neurochem Int 53:325–337. doi:10.1016/j.neuint.2008.09.004

    Article  PubMed  CAS  Google Scholar 

  13. Zhang Z, Wang Z, Zhang X et al (2005) Gene expression profile induced by oral administration of baicalin and gardenin after focal brain ischemia in rats. Acta Pharmacol Sin 26:307–314. doi:10.1111/j.1745-7254.2005.00051.x

    Article  PubMed  Google Scholar 

  14. Zhang Z, Li P, Wang Z et al (2006) A comparative study on the individual and combined effects of baicalin and jasminoidin on focal cerebral ischemia–reperfusion injury. Brain Res 1123:188–195. doi:10.1016/j.brainres.2006.09.063

    Article  PubMed  CAS  Google Scholar 

  15. Liu P, Wang J, Li Q et al (2006) Effect of baicalin on HSP70 expression of hippocampal neurons in focal brain ischemia-reperfusion injury rats. Yao Xue Xue Bao 41:619–624

    PubMed  CAS  Google Scholar 

  16. Zhang ZJ, Wang LY, Wang Z et al (2006) Pharmacological evaluation of baicalin and jasminoidin and their combination on focal cerebral ischemia-reperfusion injury. Zhongguo Zhong Yao Za Zhi 31:907–910

    PubMed  CAS  Google Scholar 

  17. Li Y, Xu Z, Ford GD et al (2007) Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia. Brain Res 1184:277–283. doi:10.1016/j.brainres.2007.09.037

    Article  PubMed  CAS  Google Scholar 

  18. Huang Z, Huang PL, Panahian N et al (1994) Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 265:1883–1885. doi:10.1126/science.7522345

    Article  PubMed  CAS  Google Scholar 

  19. Majid A, He YY, Gidday JM et al (2000) Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse strains. Stroke 31:2707–2714

    PubMed  CAS  Google Scholar 

  20. Lin TN, He YY, Wu G et al (1993) Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke 24:117–121

    PubMed  CAS  Google Scholar 

  21. Swanson RA, Morton MT, Tsao-Wu G et al (1990) A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab 10:290–293

    PubMed  CAS  Google Scholar 

  22. Matsuo Y, Onodera H, Shiga Y et al (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat: effects of neutrophil depletion. Stroke 25:1469–1475

    PubMed  CAS  Google Scholar 

  23. Lou H, Zhang X, Wei X et al (2004) Anti-inflammatory effect of hydroxyethylpuerarin on focal brain ischemia/reperfusion injury in rats. Chin J Physiol 47:197–201

    PubMed  CAS  Google Scholar 

  24. Fang S, Zhou Y, Chu L et al (2007) Spatio-temporal expression of cysteinyl leukotriene receptor-2 mRNA in rat brain after focal cerebral ischemia. Neurosci Lett 412:78–83. doi:10.1016/j.neulet.2006.10.065

    Article  PubMed  CAS  Google Scholar 

  25. Shang YZ, Miao H, Cheng JJ et al (2006) Effects of amelioration of total flavonoids from stems and leaves of Scutellaria baicalensis Georgi on cognitive deficits, neuronal damage and free radicals disorder induced by cerebral ischemia in rats. Biol Pharm Bull 29:805–810. doi:10.1248/bpb.29.805

    Article  PubMed  CAS  Google Scholar 

  26. Zhang Y, Wang X, Wang X et al (2006) Protective effect of flavonoids from Scutellaria baicalensis Georgi on cerebral ischemia injury. J Ethnopharmacol 108:355–360. doi:10.1016/j.jep.2006.05.022

    Article  PubMed  CAS  Google Scholar 

  27. Gao Z, Huang K, Yang X et al (1999) Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1472:643–650

    PubMed  CAS  Google Scholar 

  28. Cho J, Lee HK (2004) Wogonin inhibits ischemic brain injury in a rat model of permanent middle cerebral artery occlusion. Biol Pharm Bull 27:1561–1564. doi:10.1248/bpb.27.1561

    Article  PubMed  CAS  Google Scholar 

  29. Lapchak PA, Maher P, Schubert D et al (2007) Baicalein, an antioxidant 12/15-lipoxygenase inhibitor improves clinical rating scores following multiple infarct embolic strokes. Neuroscience 150:585–591. doi:10.1016/j.neuroscience.2007.09.033

    Article  PubMed  CAS  Google Scholar 

  30. Huang J, Upadhyay UM, Tamargo RJ (2006) Inflammation in stroke and focal cerebral ischemia. Surg Neurol 66:232–245. doi:10.1016/j.surneu.2005.12.028

    Article  PubMed  Google Scholar 

  31. Perera MN, Ma HK, Arakawa S et al (2006) Inflammation following stroke. J Clin Neurosci 13:1–8. doi:10.1016/j.jocn.2005.07.005

    Article  CAS  Google Scholar 

  32. Chou TC, Chang LP, Li CY et al (2003) The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia. Anesth Analg 97:1724–1729. doi:10.1213/01.ANE.0000087066.71572.3F

    Article  PubMed  CAS  Google Scholar 

  33. Kim DH, Kim HK, Park S et al (2006) Short-term feeding of baicalin inhibits age-associated NF-κB activation. Mech Ageing Dev 127:719–725. doi:10.1016/j.mad.2006.05.002

    Article  PubMed  CAS  Google Scholar 

  34. Kim YA, Lim SY, Rhee SH et al (2006) Resveratrol inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in beta-amyloid-treated C6 glioma cells. Int J Mol Med 17:1069–1075

    PubMed  CAS  Google Scholar 

  35. Ueda H, Fujita R (2004) Cell death mode switch from necrosis to apoptosis in brain. Biol Pharm Bull 27:950–955. doi:10.1248/bpb.27.950

    Article  PubMed  CAS  Google Scholar 

  36. Yuan J, Lipinski M, Degterev A (2003) Diversity in the mechanisms of neuronal cell death. Neuron 40:401–413. doi:10.1016/S0896-6273(03)00601-9

    Article  PubMed  CAS  Google Scholar 

  37. Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568

    PubMed  CAS  Google Scholar 

  38. Hartmann A, Hunot S, Michel PP et al (2000) Caspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson’s disease. Proc Natl Acad Sci USA 97:2875–2880. doi:10.1073/pnas.040556597

    Article  PubMed  CAS  Google Scholar 

  39. Chan PH (2004) Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Neurochem Res 29:1943–1949. doi:10.1007/s11064-004-6869-x

    Article  PubMed  CAS  Google Scholar 

  40. Namura S, Zhu J, Fink K et al (1998) Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci 18:3659–3668

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The internal funding from the Department of Neurosurgery, The Affiliated Union Hospital of Fujian Medical University, supported this work.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, The Affiliated Union Hospital of Fujian Medical University, 29# Xinquan Road, 350001, Fuzhou, Fujian, China

    Xian-kun Tu, Wei-zhong Yang, Song-sheng Shi, Chun-hua Wang & Chun-mei Chen

Authors
  1. Xian-kun Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei-zhong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Song-sheng Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chun-hua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chun-mei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei-zhong Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tu, Xk., Yang, Wz., Shi, Ss. et al. Neuroprotective Effect of Baicalin in a Rat Model of Permanent Focal Cerebral Ischemia. Neurochem Res 34, 1626–1634 (2009). https://doi.org/10.1007/s11064-009-9953-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-009-9953-4

Keywords

Search

Navigation