Pre‑treatment with Chrysanthemum indicum Linné extract protects pyramidal neurons from transient cerebral ischemia via increasing antioxidants in the gerbil hippocampal CA1 region

Kim,In Hye; Lee,Tae‑Kyeong; Cho,Jeong Hwi; Lee,Jae‑Chul; Park,Joon Ha; Ahn,Ji Hyeon; Shin,Bich‑Na; Chen,Bai Hui; Tae,Hyun‑Jin; Kim,Yang Hee; Kim,Jong‑Dai; Kim,Young‑Myeong; Won,Moo‑Ho; Kang,Il Jun

doi:10.3892/mmr.2017.6591

Pre‑treatment with Chrysanthemum indicum Linné extract protects pyramidal neurons from transient cerebral ischemia via increasing antioxidants in the gerbil hippocampal CA1 region

Authors:
- In Hye Kim
- Tae‑Kyeong Lee
- Jeong Hwi Cho
- Jae‑Chul Lee
- Joon Ha Park
- Ji Hyeon Ahn
- Bich‑Na Shin
- Bai Hui Chen
- Hyun‑Jin Tae
- Yang Hee Kim
- Jong‑Dai Kim
- Young‑Myeong Kim
- Moo‑Ho Won
- Il Jun Kang
View Affiliations

Affiliations: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea, Department of Physiology, College of Medicine, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea, Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China, Bio‑Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeollabuk‑do 54596, Republic of Korea, Department of Surgery, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea
Published online on: May 17, 2017 https://doi.org/10.3892/mmr.2017.6591
Pages: 133-142
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chrysanthemum indicum Linné extract (CIL) is used in herbal medicine in East Asia. In the present study, gerbils were orally pre‑treated with CIL, and changes of antioxidant enzymes including superoxide dismutase (SOD) 1 and SOD2, catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal CA1 region following 5 min of transient cerebral ischemia were investigated and the neuroprotective effect of CIL in the ischemic CA1 region was examined. SOD1, SOD2, CAT and GPX immunoreactivities were observed in the pyramidal cells of the CA1 region and their immunoreactivities were gradually decreased following ischemia‑reperfusion and barely detectable at 5 days post‑ischemia. CIL pre‑treatment significantly increased immunoreactivities of SOD1, CAT and GPX, but not SOD2, in the CA1 pyramidal cells of the sham‑operated animals. In addition, SOD1, SOD2, CAT and GPX immunoreactivities in the CA1 pyramidal cells were significantly higher compared with the ischemia‑operated animals. Furthermore, it was identified that pre‑treatment with CIL protected the CA1 pyramidal cells in the CA1 region using neuronal nuclei immunohistochemistry and Fluoro‑Jade B histofluorescence staining; the protected CA1 pyramidal cells were 67.5% compared with the sham‑operated animals. In conclusion, oral CIL pre‑treatment increased endogenous antioxidant enzymes in CA1 pyramidal cells in the gerbil hippocampus and protected the cells from transient cerebral ischemic insult. This finding suggested that CIL is promising for the prevention of ischemia‑induced neuronal damage.

View Figures

View References

1	Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, et al: Heart disease and stroke statistics-2011 update: A report from the American heart association. Circulation. 123:e18–e209. 2011. View Article : Google Scholar : PubMed/NCBI
2	Liang G, Shi B, Luo W and Yang J: The protective effect of caffeic acid on global cerebral ischemia-reperfusion injury in rats. Behav Brain Funct. 11:182015. View Article : Google Scholar : PubMed/NCBI
3	White BC, Grossman LI and Krause GS: Brain injury by global ischemia and reperfusion: A theoretical perspective on membrane damage and repair. Neurology. 43:1656–1665. 1993. View Article : Google Scholar : PubMed/NCBI
4	Butler TL, Kassed CA, Sanberg PR, Willing AE and Pennypacker KR: Neurodegeneration in the rat hippocampus and striatum after middle cerebral artery occlusion. Brain Res. 929:252–260. 2002. View Article : Google Scholar : PubMed/NCBI
5	Crain BJ, Westerkam WD, Harrison AH and Nadler JV: Selective neuronal death after transient forebrain ischemia in the Mongolian gerbil: A silver impregnation study. Neuroscience. 27:387–402. 1988. View Article : Google Scholar : PubMed/NCBI
6	Kirino T: Delayed neuronal death. Neuropathology. 20:(Suppl). 95–97. 2000. View Article : Google Scholar
7	Lewén A, Matz P and Chan PH: Free radical pathways in CNS injury. J Neurotrauma. 17:871–890. 2000. View Article : Google Scholar : PubMed/NCBI
8	Lee JC and Won MH: Neuroprotection of antioxidant enzymes against transient global cerebral ischemia in gerbils. Anat Cell Biol. 47:149–156. 2014. View Article : Google Scholar : PubMed/NCBI
9	Park JH, Park OK, Yan B, Ahn JH, Kim IH, Lee JC, Kwon SH, Yoo KY, Lee CH, Hwang IK, et al: Neuroprotection via maintenance or increase of antioxidants and neurotrophic factors in ischemic gerbil hippocampus treated with tanshinone I. Chin Med J (Engl). 127:3396–3405. 2014.PubMed/NCBI
10	Chan PH: Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab. 21:2–14. 2001. View Article : Google Scholar : PubMed/NCBI
11	Delanty N and Dichter MA: Antioxidant therapy in neurologic disease. Arch Neurol. 57:1265–1270. 2000. View Article : Google Scholar : PubMed/NCBI
12	Pastore A, Petrillo S, Piermarini E and Piemonte F: Systemic redox biomarkers in neurodegenerative diseases. Curr Drug Metab. 16:46–70. 2015. View Article : Google Scholar : PubMed/NCBI
13	Duan X, Wang W, Liu X, Yan H, Dai R and Lin Q: Neuroprotective effect of ethyl acetate extract from gastrodia elata against transient focal cerebral ischemia in rats induced by middle cerebral artery occlusion. J Tradit Chin Med. 35:671–678. 2015. View Article : Google Scholar : PubMed/NCBI
14	Surapaneni S, Prakash T, Ansari M, Manjunath P, Kotresha D and Goli D: Study on cerebroprotective actions of Clerodendron glandulosumleaves extract against long term bilateral common carotid artery occlusion in rats. Biomed Pharmacother. 80:87–94. 2016. View Article : Google Scholar : PubMed/NCBI
15	Cheng W, Li J, You T and Hu C: Anti-inflammatory and immunomodulatory activities of the extracts from the inflorescence of Chrysanthemum indicum Linné. J Ethnopharmacol. 101:334–337. 2005. View Article : Google Scholar : PubMed/NCBI
16	Lee DY, Choi G, Yoon T, Cheon MS, Choo BK and Kim HK: Anti-inflammatory activity of Chrysanthemum indicum extract in acute and chronic cutaneous inflammation. J Ethnopharmacol. 123:149–154. 2009. View Article : Google Scholar : PubMed/NCBI
17	Shunying Z, Yang Y, Huaidong Y, Yue Y and Guolin Z: Chemical composition and antimicrobial activity of the essential oils of Chrysanthemum indicum. J Ethnopharmacol. 96:151–158. 2005. View Article : Google Scholar : PubMed/NCBI
18	Zhang C, Qin MJ, Shu P, Hong JL, Lu L and He DX: Chemical variations of the essential oils in flower heads of Chrysanthemum indicum L. From China. Chem Biodivers. 7:2951–2962. 2010. View Article : Google Scholar : PubMed/NCBI
19	Cheon MS, Yoon T, Lee DY, Choi G, Moon BC, Lee AY, Choo BK and Kim HK: Chrysanthemum indicum Linné extract inhibits the inflammatory response by suppressing NF-kappaB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophages. J Ethnopharmacol. 122:473–477. 2009. View Article : Google Scholar : PubMed/NCBI
20	Dekanski D, Selaković V, Piperski V, Radulović Z, Korenić A and Radenović L: Protective effect of olive leaf extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in Mongolian gerbils. Phytomedicine. 18:1137–1143. 2011. View Article : Google Scholar : PubMed/NCBI
21	Rocher MN, Carré D, Spinnewyn B, Schulz J, Delaflotte S, Pignol B, Chabrier PE and Auguet M: Long-term treatment with standardized Ginkgo biloba extract (EGb 761) attenuates cognitive deficits and hippocampal neuron loss in a gerbil model of vascular dementia. Fitoterapia. 82:1075–1080. 2011. View Article : Google Scholar : PubMed/NCBI
22	Yoo KY, Kim IH, Cho JH, Ahn JH, Park JH, Lee JC, Tae HJ, Kim DW, Kim JD, Hong S, et al: Neuroprotection of Chrysanthemum indicum Linne against cerebral ischemia/reperfusion injury by anti-inflammatory effect in gerbils. Neural Regen Res. 11:270–277. 2016. View Article : Google Scholar : PubMed/NCBI
23	Kim IH, Yan BC, Park JH, Yeun GH, Yim Y, Ahn JH, Lee JC, Hwang IK, Cho JH, Kim YM, et al: Neuroprotection of a novel synthetic caffeic acid-syringic acid hybrid compound against experimentally induced transient cerebral ischemic damage. Planta Med. 79:313–321. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kim DW, Lee JC, Cho JH, Park JH, Ahn JH, Chen BH, Shin BN, Tae HJ, Seo JY, Cho JH, et al: Neuroprotection of ischemic preconditioning is mediated by anti-inflammatory, not pro-inflammatory, cytokines in the gerbil hippocampus induced by a subsequent lethal transient cerebral ischemia. Neurochem Res. 40:1984–1995. 2015. View Article : Google Scholar : PubMed/NCBI
25	Candelario-Jalil E, Alvarez D, Merino N and León OS: Delayed treatment with nimesulide reduces measures of oxidative stress following global ischemic brain injury in gerbils. Neurosci Res. 47:245–253. 2003. View Article : Google Scholar : PubMed/NCBI
26	Lee JC, Kim IH, Cho GS, Park JH, Ahn JH, Yan BC, Kwon HM, Kim YM, Cheon SH, Cho JH, et al: Ischemic preconditioning-induced neuroprotection against transient cerebral ischemic damage via attenuating ubiquitin aggregation. J Neurol Sci. 336:74–82. 2014. View Article : Google Scholar : PubMed/NCBI
27	Petito CK, Olarte JP, Roberts B, Nowak TS Jr and Pulsinelli WA: Selective glial vulnerability following transient global ischemia in rat brain. J Neuropathol Exp Neurol. 57:231–238. 1998. View Article : Google Scholar : PubMed/NCBI
28	Sugawara T, Fujimura M, Morita-Fujimura Y, Kawase M and Chan PH: Mitochondrial release of cytochrome c corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia. J Neurosci. 19:RC391999.PubMed/NCBI
29	Zhang QG, Wang R, Han D, Dong Y and Brann DW: Role of Rac1 GTPase in JNK signaling and delayed neuronal cell death following global cerebral ischemia. Brain Res. 1265:138–147. 2009. View Article : Google Scholar : PubMed/NCBI
30	Levine S and Sohn D: Cerebral ischemia in infant and adult gerbils. Relation to incomplete circle of Willis. Arch Pathol. 87:315–317. 1969.PubMed/NCBI
31	Martínez NS, Machado JM, Pérez-Saad H, Coro-Antich RM, Berlanga-Acosta JA, Salgueiro SR, Illera GG, Alba JS and del Barco DG: Global brain ischemia in Mongolian gerbils: Assessing the level of anastomosis in the cerebral circle of Willis. Acta Neurobiol Exp (Wars). 72:377–384. 2012.PubMed/NCBI
32	Kim IH, Yoo KY, Park JH, Yan BC, Ahn JH, Lee JC, Kwon HM, Kim JD, Kim YM, You SG, et al: Comparison of neuroprotective effects of extract and fractions from Agarum clathratum against experimentally induced transient cerebral ischemic damage. Pharm Biol. 52:335–343. 2014. View Article : Google Scholar : PubMed/NCBI
33	Park JH, Shin BN, Chen BH, Kim IH, Ahn JH, Cho JH, Tae HJ, Lee JC, Lee CH, Kim YM, et al: Neuroprotection and reduced gliosis by atomoxetine pretreatment in a gerbil model of transient cerebral ischemia. J Neurol Sci. 359:373–380. 2015. View Article : Google Scholar : PubMed/NCBI
34	Numagami Y, Sato S and Ohnishi ST: Attenuation of rat ischemic brain damage by aged garlic extracts: A possible protecting mechanism as antioxidants. Neurochem Int. 29:135–143. 1996. View Article : Google Scholar : PubMed/NCBI
35	Tu Q, Wang R, Ding B, Zhong W and Cao H: Protective and antioxidant effect of Danshen polysaccharides on cerebral ischemia/reperfusion injury in rats. Int J Biol Macromol. 60:268–271. 2013. View Article : Google Scholar : PubMed/NCBI
36	Chan PH: Oxygen radicals in focal cerebral ischemia. Brain Pathol. 4:59–65. 1994. View Article : Google Scholar : PubMed/NCBI
37	Rodrigo R, Fernández-Gajardo R, Gutiérrez R, Matamala JM, Carrasco R, Miranda-Merchak A and Feuerhake W: Oxidative stress and pathophysiology of ischemic stroke: Novel therapeutic opportunities. CNS Neurol Disord Drug Targets. 12:698–714. 2013. View Article : Google Scholar : PubMed/NCBI
38	Mantha AK, Sarkar B and Tell G: A short review on the implications of base excision repair pathway for neurons: Relevance to neurodegenerative diseases. Mitochondrion. 16:38–49. 2014. View Article : Google Scholar : PubMed/NCBI
39	Sugawara T and Chan PH: Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid Redox Signal. 5:597–607. 2003. View Article : Google Scholar : PubMed/NCBI
40	Park JH, Cho JH, Kim IH, Ahn JH, Lee JC, Chen BH, Shin BN, Tae HJ, Yoo KY, Hong S, et al: Oenanthe Javanica extract protects against experimentally induced ischemic neuronal damage via its antioxidant effects. Chin Med J (Engl). 128:2932–2937. 2015. View Article : Google Scholar : PubMed/NCBI
41	Kim TW, Kim YJ, Park SR, Seo CS, Ha H, Shin HK and Jung JY: Chrysanthemum indicum attenuates cisplatin-induced nephrotoxicity both in vivo and in vitro. Nat Prod Commun. 10:397–402. 2015.PubMed/NCBI
42	Murakami K, Kondo T, Epstein CJ and Chan PH: Overexpression of CuZn-superoxide dismutase reduces hippocampal injury after global ischemia in transgenic mice. Stroke. 28:1797–1804. 1997. View Article : Google Scholar : PubMed/NCBI
43	Chan PH, Kawase M, Murakami K, Chen SF, Li Y, Calagui B, Reola L, Carlson E and Epstein CJ: Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion. J Neurosci. 18:8292–8299. 1998.PubMed/NCBI
44	Kondo T, Reaume AG, Huang TT, Carlson E, Murakami K, Chen SF, Hoffman EK, Scott RW, Epstein CJ and Chan PH: Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J Neurosci. 17:4180–4189. 1997.PubMed/NCBI
45	Murakami K, Kondo T, Kawase M, Li Y, Sato S, Chen SF and Chan PH: Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency. J Neurosci. 18:205–213. 1998.PubMed/NCBI
46	Kim DW, Kim DS, Kim MJ, Kwon SW, Ahn EH, Jeong HJ, Sohn EJ, Dutta S, Lim SS, Cho SW, et al: Imipramine enhances neuroprotective effect of PEP-1-Catalase against ischemic neuronal damage. BMB Rep. 44:647–652. 2011. View Article : Google Scholar : PubMed/NCBI
47	Kim JE, Jun S, Song M, Kim JH and Song YJ: The extract of Chrysanthemum indicum Linne inhibits EBV LMP1-induced NF-κB activation and the viability of EBV-transformed lymphoblastoid cell lines. Food Chem Toxicol. 50:1524–1528. 2012. View Article : Google Scholar : PubMed/NCBI
48	Kim IS, Ko HM, Koppula S, Kim BW and Choi DK: Protective effect of Chrysanthemum indicum Linne against 1-methyl-4-phenylpridinium ion and lipopolysaccharide-induced cytotoxicity in cellular model of Parkinson's disease. Food Chem Toxicol. 49:963–973. 2011. View Article : Google Scholar : PubMed/NCBI