Gastrodin ameliorates subacute phase cerebral ischemia‑reperfusion injury by inhibiting inflammation and apoptosis in rats

Liu,Bo; Li,Fei; Shi,Jingshan; Yang,Danli; Deng,Yuanyuan; Gong,Qihai

doi:10.3892/mmr.2016.5785

Gastrodin ameliorates subacute phase cerebral ischemia‑reperfusion injury by inhibiting inflammation and apoptosis in rats

Authors:
- Bo Liu
- Fei Li
- Jingshan Shi
- Danli Yang
- Yuanyuan Deng
- Qihai Gong
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Affiliations: Key Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
Published online on: September 26, 2016 https://doi.org/10.3892/mmr.2016.5785
Pages: 4144-4152
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastrodin (GAS), which is extracted from the Chinese herbal medicine Gastrodia elata Blume, has long been used to improve stroke, epilepsy, dizziness and dementia. However, the effects and underlying mechanisms of GAS on subacute phase cerebral ischemia‑reperfusion (I/R) injury remain unknown. The aim of the present study was to investigate the effects and mechanisms of GAS on cerebral I/R injury in rats. The rats were pretreated with GAS by gavage for 7 days followed by I/R surgery, and were then treated with GAS for 7 days after I/R surgery. Neurological deficits were assessed on days 1, 3 and 7 post‑cerebral I/R injury. 2,3,5‑Triphenyltetrazolium chloride staining was using to measure the infarct volume; morphological alterations were observed by hematoxylin and eosin staining under an optical microscope; apoptosis in the hippocampus and cortex was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining; and the level of mRNA and protein expression was tested by reverse transcription‑quantitative polymerase chain reation and western blot analysis, respectively. GAS markedly attenuated I/R‑induced disability and histological damage, alleviated neuronal apoptosis, and reduced the mRNA and protein expression levels of inflammatory and proapoptotic factors, including interleukin‑1β, cyclooxygenase‑2, inducible nitric oxide synthase and cleaved caspase‑3. These findings suggested that GAS may ameliorate subacute phase cerebral I/R injury by inhibiting inflammation and apoptosis in rats; therefore, GAS may be considered a potential candidate for the treatment of cerebral ischemia.

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1	Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL and Parag V: Worldwide stroke incidence and early case fatality reported in 56 population-based studies: A systematic review. Lancet Neurol. 8:355–369. 2009. View Article : Google Scholar : PubMed/NCBI
2	Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, et al: Heart disease and stroke statistics-2008 update: A report from the American heart association statistics committee and stroke statistics subcommittee. Circulation. 117:e25–e146. 2008. View Article : Google Scholar : PubMed/NCBI
3	Strosznajder RP, Czubowicz K, Jesko H and Strosznajder JB: Poly (ADP-ribose) metabolism in brain and its role in ischemia pathology. Mol Neurobiol. 41:187–196. 2010. View Article : Google Scholar : PubMed/NCBI
4	Gonzalez CL, Gharbawie OA and Kolb B: Chronic low-dose administration of nicotine facilitates recovery and synaptic change after focal ischemia in rats. Neuropharmacology. 50:777–787. 2006. View Article : Google Scholar : PubMed/NCBI
5	Mehta SL, Manhas N and Raghubir R: Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev. 54:34–66. 2007. View Article : Google Scholar : PubMed/NCBI
6	Wu Pf, Zhang Z, Wang F and Chen JG: Natural compounds from traditional medicinal herbs in the treatment of cerebral ischemia/reperfusion injury. Acta Pharmacol Sin. 31:1523–1531. 2010. View Article : Google Scholar : PubMed/NCBI
7	Zhu H, Dai P, Zhang W, Chen E, Han W, Chen C and Cui Y: Enzymic synthesis of gastrodin through microbial transformation and purification of gastrodin biosynthesis enzyme. Biol Pharm Bull. 33:1680–1684. 2010. View Article : Google Scholar : PubMed/NCBI
8	Kumar H, Kim IS, More SV, Kim BW, Bahk YY and Choi DK: Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson's disease model. Evid-Based Compl Alt. 2013:5140952013. View Article : Google Scholar
9	Lin LC, Chen YF, Lee WC, Wu YT and Tsai TH: Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood, brain and bile by microdialysis coupled to LC-MS/MS. J Pharm Biomed Anal. 48:909–917. 2008. View Article : Google Scholar : PubMed/NCBI
10	Zeng X, Zhang S, Zhang L, Zhang K and Zheng X: A study of the neuroprotective effect of the phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro. Planta Med. 72:1359–1365. 2006. View Article : Google Scholar : PubMed/NCBI
11	Xu X, Lu Y and Bie X: Protective effects of gastrodin on hypoxia-induced toxicity in primary cultures of rat cortical neurons. Planta Med. 73:650–654. 2007. View Article : Google Scholar : PubMed/NCBI
12	Bie X, Chen Y, Han J, Dai H, Wan H and Zhao T: Effects of gastrodin on amino acids after cerebral ischemia-reperfusion injury in rat striatum. Asia Pac J Clin Nutr. 16:305–308. 2007.PubMed/NCBI
13	Dai JN, Zong Y, Zhong LM, Li YM, Zhang W, Bian LG, Ai QL, Liu YD, Sun J and Lu D: Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways. PloS One. 6:e218912011. View Article : Google Scholar : PubMed/NCBI
14	Wang Y, Wu Z, Liu X and Fu Q: Gastrodin ameliorates Parkinson's disease by downregulating connexin 43. Mol Med Rep. 8:585–590. 2013.PubMed/NCBI
15	Peng Z, Wang H, Zhang R, Chen Y, Xue F, Nie H, Chen Y, Wu D, Wang Y, Wang H and Tan Q: Gastrodin ameliorates anxiety-like behaviors and inhibits IL-1beta level and p38 MAPK phosphorylation of hippocampus in the rat model of posttraumatic stress disorder. Physiol Res. 62:537–545. 2013.PubMed/NCBI
16	Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL and Bartkowski H: Rat middle cerebral artery occlusion: Evaluation of the model and development of a neurologic examination. Stroke. 17:472–476. 1986. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Hoffman GE, Merchenthaler I and Zup SL: Neuroprotection by ovarian hormones in animal models of neurological disease. Endocrine. 29:217–231. 2006. View Article : Google Scholar : PubMed/NCBI
19	Boyko M, Zlotnik A, Gruenbaum BF, Gruenbaum SE, Ohayon S, Goldsmith T, Kotz R, Leibowitz A, Sheiner E, Shapira Y and Teichberg VI: An experimental model of focal ischemia using an internal carotid artery approach. J Neurosci Methods. 193:246–253. 2010. View Article : Google Scholar : PubMed/NCBI
20	Kakarieka A, Schakel E and Fritze J: Clinical experiences with nimodipine in cerebral ischemia. J Neural Trans Suppl. 43:13–21. 1994.
21	Aslan A, Gurelik M, Cemek M, Goksel HM and Buyukokuroglu ME: Nimodipine can improve cerebral metabolism and outcome in patients with severe head trauma. Pharmacol Res. 59:120–124. 2009. View Article : Google Scholar : PubMed/NCBI
22	Fogelholm R, Erilä T, Palomäki H, Murros K and Kaste M: Effect of nimodipine on final infarct volume after acute ischemic stroke. Cerebrovasc Dis. 10:189–193. 2000. View Article : Google Scholar : PubMed/NCBI
23	Babu CS and Ramanathan M: Post-ischemic administration of nimodipine following focal cerebral ischemic-reperfusion injury in rats alleviated excitotoxicity, neurobehavioural alterations and partially the bioenergetics. Int J Dev Neurosci. 29:93–105. 2011. View Article : Google Scholar : PubMed/NCBI
24	Muir KW, Tyrrell P, Sattar N and Warburton E: Inflammation and ischaemic stroke. Curr Opin Neurol. 20:334–342. 2007. View Article : Google Scholar : PubMed/NCBI
25	Ye YL, Shi WZ, Zhang WP, Wang ML, Zhou Y, Fang SH, Liu LY, Zhang Q, Yu YP and Wei EQ: Cilostazol, a phosphodiesterase 3 inhibitor, protects mice against acute and late ischemic brain injuries. Eur J Pharmacol. 557:23–31. 2007. View Article : Google Scholar : PubMed/NCBI
26	Simard JM, Kent TA, Chen M, Tarasov KV and Gerzanich V: Brain oedema in focal ischaemia: Molecular pathophysiology and theoretical implications. Lancet Neurol. 6:258–268. 2007. View Article : Google Scholar : PubMed/NCBI
27	Jin R, Yang G and Li G: Inflammatory mechanisms in ischemic stroke: Role of inflammatory cells. J Leukoc Biol. 87:779–789. 2010. View Article : Google Scholar : PubMed/NCBI
28	Li F, Gong Q, Wang L and Shi J: Osthole attenuates focal inflammatory reaction following permanent middle cerebral artery occlusion in rats. Biol Pharm Bull. 35:1686–1690. 2012. View Article : Google Scholar : PubMed/NCBI
29	Maddahi A and Edvinsson L: Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway. J Neuroinflammation. 7:142010. View Article : Google Scholar : PubMed/NCBI
30	Jiang MH, Kaku T, Hada J and Hayashi Y: 7-Nitroindazole reduces nitric oxide concentration in rat hippocampus after transient forebrain ischemia. Eur J Pharmacol. 380:117–121. 1999. View Article : Google Scholar : PubMed/NCBI
31	Iadecola C, Forster C, Nogawa S, Clark HB and Ross ME: Cyclooxygenase-2 immunoreactivity in the human brain following cerebral ischemia. Acta Neuropathol. 98:9–14. 1999. View Article : Google Scholar : PubMed/NCBI
32	Lujia Y, Xin L, Shiquan W, Yu C, Shuzhuo Z and Hong Z: Ceftriaxone pretreatment protects rats against cerebral ischemic injury by attenuating microglial activation-induced IL-1β expression. Int J Neurosci. 124:657–665. 2014. View Article : Google Scholar : PubMed/NCBI
33	Hartmann A, Hunot S, Michel PP, Muriel MP, Vyas S, Faucheux BA, Mouatt-Prigent A, Turmel H, Srinivasan A, Ruberg M, et al: Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. P Natl Acad Sci USA. 97:2875–2880. 2000. View Article : Google Scholar
34	Chen J, Nagayama T, Jin K, Stetler RA, Zhu RL, Graham SH and Simon RP: Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. J Neurosci. 18:4914–4928. 1998.PubMed/NCBI