Neuroprotective Effects of Scutellarin against Hypoxic-Ischemic-Induced Cerebral Injury via Augmentation of Antioxidant Defense Capacity

10.4077/CJP.2011.AMM059

Hong Guo；Li-Min Hu；Shao-Xia Wang；Yu-Lin Wang；Fang Shi；Hui Li；Yang Liu；Li-Yuan Kang；Xiu-Mei Gao

scutellarin ； neuroprotective effects ； antioxidant capacity

The Chinese Journal of Physiology

54卷6期（2011 / 12 / 01）

399 - 405

英文

An increasing number of studies has indicated that hypoxic-ischemic-induced cerebral injury is partly mediated via oxidative stress. Recent researches have focused on searching for drug and herbal manipulations to protect against hypoxic-ischemic-induced oxidative cell damage. Scutellarin is a flavonoid derived from the Erigeron breviscapus (vant.) and has been reported to exhibit neuroprotective properties. However, its precise mechanism, particularly its antioxidation mechanism, remains elusive. In the present study, we investigated the neuroprotective effects of scutellarin on middle cerebral artery occlusion (MCAO)-induced brain damage in rats, and oxygen-glucose deprivation (OGD)-induced toxicity in primary culture of rat cortical neurons. In vivo, intraperitoneal injections of scutellarin (20 and 60 mg/kg) improved the neurological score and diminished the percentage of brain infarct volume. At the same time, scutellarin significantly increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level in ischemic brain tissues, enhancing endogenous antioxidant activity. Moreover, pretreatment of scutellarin (25, 50 and 100 μM) protected neurons against lethal stimuli, decreased the percentage of apoptotic cells and inhibited reactive oxygen species (ROS) generation in OGD-induced primary cortical neurons in vitro. These results suggest that the preventive and therapeutic potential of scutellarin in cerebral injury patients is, at least in part, ascribed to augmentation of cellular antioxidant defense capacity.

1. Akpinar, D.,Yargiçoğlu, P.,Derin, N.,Alicigüzel, Y.,Ağar, A.(2008).The effect of lipoic acid on antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress.Physiol. Res.,57,893-901.
2. Antonelli, T.,Tomasini, M.C.,Fournier, J.,Mazza, R.,Tanganelli, S.,Pirondi, S.,Fuxe, K.,Luca, F.(2008).Neurotensin receptor involvement in the rise of extracellular glutamate levels and apoptotic nerve cell death in primary cortical cultures after oxygen and glucose deprivation.Cereb. Cortex,18,1748-1757.
3. Beck, J.,Lenart, B.,Kintner, D.B.,Sun, D.(2003).Na-K-Cl cotransporter contributes to glutamate-mediated excitotoxicity.J. Neurosci.,23,5061-5068.
4. Chan, P.H.(2001).Reactive oxygen radicals in signaling and damage in the ischemic brain.J. Cereb. Blood Flow Metab.,21,2-14.
5. Chandrashekhar, V.M.,Ranpariya, V.L.,Ganapaty, S.,Parashar, A.,Muchandi, A.A.(2010).Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats.J. Ethnopharmacol.,127,645-651.
6. Ding, R.F.,Li, Z.X.(2009).The clinical application of agents breviscapine.Tianjin Pharmacy,21,60-63.
7. Domoki, F.,Kis, B.,Gáspár, T.,Snipes, J.A.,Parks, J.S.,Bari, F.,Busija, D.W.(2009).Rosuvastatin induces delayed preconditioning against oxygen-glucose deprivation in cultured cortical neurons.Am. J. Physiol. Cell Physiol.,296,97-105.
8. Ga, S.R.,Wan, P.(2009).Progress in clinical application of breviscapine.Yunnan J. Tradi. Chinese Med.,30,67-68.
9. Gilgun-Sherki, Y.,Rosenbaum, Z.,Melamed, E.,Offen, D.(2002).Antioxidant therapy in acute central nervous system injury: current state.Pharmacol. Rev.,54,271-284.
10. Hu, X.M.,Zhou, M.M.,Hu, X.M.,Zeng, F.D.(2005).Neuroprotective effects of scutellarin on rat neuronal damage induced by cerebral ischemia/reperfusion.Acta Pharmacol. Sin.,26,1454-1459.
11. Imai, H.,Masayasu, H.,Dewar, D.(2001).Ebselen protects both gray and white matter in a rodent model of focal cerebral ischemia.Stroke,32,2149-2154.
12. Lin, Z.,Zhu, D.,Yan, Y.,Yu, B.,Wang, Q.,Shen, P.,Ruan, K.(2008).An antioxidant phytotherapy to rescue neuronal oxidative stress.Evid-Based Complement Altern. Med.,2011,1-7.
13. Liu, H.,Yang, X.L.,Wang, Y.,Tang, X.Q.,Jiang, D.Y.,Xu, H.B.(2003).Protective effects of scutellarin on superoxide-induced oxidative stress in rat cortical synaptosomes.Acta Pharmacol. Sin.,24,1113-1117.
14. Longa, E.Z.,Weinstein, P.R.,Carlson, S.,Cummins, R.(1989).Reversible middle cerebral artery occlusion without craniectomy in rats.Stroke,20,84-91.
15. Mao, P.,Ardeshiri, A.,Jacks, R.,Yang, S.,Hurn, P.D.,Alkayed, N.J.(2007).Mitochondrial mechanism of neuroprotection by CART.Eur. J. Neurosci.,26,624-632.
16. Shen, C.C.,Huang, H.M.,Ou, H.C.,Chen, H.L.,Chen, W.C.,Jeng, K.C.(2004).Protective effect of nicotinamide on neuronal cells under oxygen and glucose deprivation and hypoxia/reoxygenation.J. Biomed. Sci.,11,472-481.
17. Shi, H.,Liu, K.J.(2006).Effects of glucose concentration on redox status in rat primary cortical neurons under hypoxia.Neurosci. Lett.,410,57-61.
18. Xu, W.,Zha, R.P.,Wang, W.Y.,Wang, Y.P.(2007).Effects of scutellarin on PKCγ in PC12 cell injury induced by oxygen and glucose deprivation.Acta Pharmacol. Sin.,28,1573-1579.
19. Ying, W.(1996).A new hypothesis of neurodegenerative diseases: the deleterious network hypothesis.Med. Hypotheses,47,307-313.
20. Zhang, H.F.,Hu, X.M.,Wang, L.X.,Xu, S.Q.,Zeng, F.D.(2009).Protective effects of scutellarin against cerebral ischemia in rats: evidence for inhibition of the apoptosis-inducing factor pathway.Planta Med.,75,121-126.
21. Zhou, X.M.,Cao, Y.L.,Dou, D.Q.(2006).Protective effect of ginsenoside-Re against cerebral ischemia/reperfusion damage in rats.Biol. Pharm. Bull.,29,2502-2505.
22. Zhu, Y.Z.,Huang, S.H.,Tan, B.K.,Sun, J.,Whiteman, M.,Zhu, Y.C.(2004).Antioxidants in Chinese herbal medicines: a biochemical perspective.Nat. Prod. Rep.,21,478-489.

1. Lai, Yih-Loong,Chen, Mei-Jung,Chen, Kang-Hua(2012).Oxygen Radicals and Substance P in Perinatal Hypoxia-Exaggerated, Monocrotaline-Induced Pulmonary Hypertension.中國生理學雜誌,55(2),82-90.
2. Tirumanyam, Madhavi,Nannepaga, John Sushma,Kuo, Chia-Hua,Korivi, Mallikarjuna,Bommavaram, Mahitha(2014).Neuroprotective Effects of Bacopa monniera Whole-Plant Extract against Aluminum-Induced Hippocampus Damage in Rats: Evidence from Electron Microscopic Images.中國生理學雜誌,57(5),279-285.