Planta Med 2009; 75(14): 1499-1504
DOI: 10.1055/s-0029-1185806
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Protective Effects of Echinacoside, One of the Phenylethanoid Glycosides, on H2O2-Induced Cytotoxicity in PC12 Cells

Rong Kuang1 , 2 , Yiguo Sun1 , Wei Yuan1 , Li Lei3 , Xiaoxiang Zheng1
  • 1Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering, Ministry of Education, Zhejiang University (Yuquan Campus), Hang Zhou, People's Republic of China
  • 2Zhejiang Food and Drug Institute for Control, Hang Zhou, People's Republic of China
  • 3Sinphar Tianli Pharmaceutical Co., Ltd., Yuhang Economic Development Zone, Hang Zhou, People's Republic of China
Further Information

Publication History

received January 21, 2009 revised May 7, 2009

accepted May 14, 2009

Publication Date:
22 June 2009 (online)

Abstract

We have investigated the protective effects of echinacoside (ECH), one of the phenylethanoid glycosides, on H2O2-induced cytotoxicity in the rat pheochromocytoma cell line (PC12 cells). Our data show that application of ECH to H2O2-injured PC12 cells (HIPCs) increased cell viability and decreased the apoptotic ratio. Flow cytometry (FCM) and laser scanning confocal microscopy (LSCM) analysis suggested that ECH exerted its inhibitory effects on the formation of reactive oxygen species (ROS) and the accumulation of intracellular free Ca2+ ([Ca2+]i). In addition, ECH elevated the mitochondrial membrane potential (MMP) in HIPCs. Furthermore, Western blot analysis revealed that ECH prevented an H2O2-induced increase of the Bax/Bcl-2 ratio by down-regulating Bax protein expression and upregulating Bcl-2 protein expression. In summary, ECH showed significant neuroprotective effects on HIPCs through the mitochondrial apoptotic pathway, and could be a potential candidate for intervention in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

References

  • 1 Butterfield D A, Howard B, Yatin S, Koppal T, Drake J, Hensley K, Aksenov M, Aksenova M, Subramaniam R, Varadarajan S, Harris-White M E, Pedigo Jr N W, Carney J M. Elevated oxidative stress in models of normal brain aging and Alzheimer's disease.  Life Sci. 1999;  65 1883-1892
  • 2 Mattson M P. Pathways towards and away from Alzheimer's disease.  Nature. 2004;  430 631-639
  • 3 Oikawa S, Hirosawa I, Tada-Oikawa S, Furukawa A, Nishiura K, Kawanishi S. Mechanism for manganese enhancement of dopamine-induced oxidative DNA damage and neuronal cell death.  Free Radic Biol Med. 2006;  41 748-756
  • 4 Warner D S, Sheng H, Batinić-Haberle I. Oxidants, antioxidants and the ischemic brain.  J Exp Biol. 2004;  207 3221-3231
  • 5 Zhu D, Lai Y, Shelat P B, Hu C, Sun G Y, Lee J C. Phospholipases A2 mediate amyloid-beta peptide-induced mitochondrial dysfunction.  J Neurosci. 2006;  26 11111-11119
  • 6 Zeng X H, Zhang S M, Zhang L, Zhang K P, Zheng X X. A study of the neuroprotective effect of the phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro.  Planta Med. 2006;  72 1359-1365
  • 7 Greene L A, Tischler A S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.  Proc Natl Acad Sci USA. 1976;  73 2424-2428
  • 8 Li R C, Morris M W, Lee S K, Pouranfar F, Wang Y, Gozal D. Neuroglobin protects PC12 cells against oxidative stress.  Brain Res. 2008;  23 159-166
  • 9 Kim J W, Li M H, Jang J H, Na H K, Song N Y, Lee C, Johnson J A, Surh Y J. 15-Deoxy-delta (12,14)-prostaglandin J (2) rescues PC12 cells from H2O2-induced apoptosis through Nrf2-mediated upregulation of heme oxygenase-1: potential roles of Akt and ERK1/2.  Biochem Pharmacol. 2008;  76 1577-1589
  • 10 Koo K A, Sung S H, Park J H, Kim S H, Lee K Y, Kim Y C. In vitro neuroprotective activities of phenylethanoid glycosides from Callicarpa dichotoma.  Planta Med. 2005;  71 778-780
  • 11 Mostafa M, Nahar N, Mosihuzzaman M, Makhmoor T, Choudhary M I, Rahman A U. Free radical scavenging phenylethanoid glycosides from Leucas indica Linn.  Nat Prod Res. 2007;  21 354-361
  • 12 Liu F X, Wang X W, Luo L, Xin H, Wang X F. The effects of glycosides of cistanche on learning and memory in β-amyloid peptide induced Alzheimers disease in mice and its possible mechanism.  Chin Pharmacol Bull. 2006;  22 595-599
  • 13 Mourboul A, Mao X M, Rena K, Ma S Y, Leininger M, Gérard S. Antioxidant property of general cistanosides in human HL‐60 cell line.  Chin Pharmacol Bull. 2008;  24 362-364
  • 14 Deng M, Zhao J Y, Tu P F, Jiang Y, Li Z B, Wang Y H. Echinacoside rescues the SHSY5Y neuronal cells from TNFalpha-induced apoptosis.  Eur J Pharmacol. 2004;  505 11-18
  • 15 Geng X, Tian X, Tu P, Pu X. Neuroprotective effects of echinacoside in the mouse MPTP model of Parkinson's disease.  Eur J Pharmacol. 2007;  564 66-74
  • 16 Wu Y, Li L, Wen T, Li Y Q. Protective effects of echinacoside on carbon tetrachloride-induced hepatotoxicity in rats.  Toxicology. 2007;  232 50-56
  • 17 Hong H, Liu G Q. Protection against hydrogen peroxide-induced cytotoxicity in PC12 cells by scutellarin.  Life Sci. 2004;  74 2959-2963
  • 18 Samuilov V D, Kiselevsky D B, Shestak A A, Nesov A V, Vasil'ev L A. Reactive oxygen species in programmed death of pea guard cells.  Biochemistry. 2008;  73 1076-1084
  • 19 Zhang L, Yu H, Sun Y, Lin X, Chen B, Tan C, Cao G, Wang Z. Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells.  Eur J Pharmacol. 2007;  564 18-25
  • 20 Colognato R, Laurenza I, Fontana I, Coppedé F, Siciliano G, Coecke S, Aruoma O I, Benzi L, Migliore L. Modulation of hydrogen peroxide-induced DNA damage, MAPKs activation and cell death in PC12 by ergothioneine.  Clin Nutr. 2006;  25 135-145
  • 21 Nguyen T T, Cho S O, Ban J Y, Kim J Y, Ju H S, Koh S B, Song K S, Seong Y H. Neuroprotective effect of Sanguisorbae Radix against oxidative stress-induced brain damage: in vitro and in vivo.  Biol Pharm Bull. 2008;  31 2028-2035
  • 22 Cassarino D S, Parks J K, Parker Jr W D, Bennett Jr J P. The parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism.  Biochim Biophys Acta. 1999;  1453 49-62
  • 23 Guo S, Bezard E, Zhao B. Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS‐NO pathway.  Free Radic Biol Med. 2005;  39 682-695
  • 24 Tretter L, Takacs K, Kövér K, Adam-Vizi V. Stimulation of H2O2 generation by calcium in brain mitochondria respiring on alpha-glycerophosphate.  J Neurosci Res. 2007;  85 3471-3479
  • 25 Liu C S, Chen N H, Zhang J T. Protection of PC12 cells from hydrogen peroxide-induced cytotoxicity by salvianolic acid B, a new compound isolated from Radix Salviae miltiorrhizae.  Phytomedicine. 2007;  14 492-497
  • 26 Soane L, Siegel Z T, Schuh R A, Fiskum G. Postnatal developmental regulation of Bcl-2 family proteins in brain mitochondria.  J Neurosci Res. 2008;  86 1267-1276
  • 27 Lud Cadet J, Harrington B, Ordonez S. Bcl-2 over expression attenuates dopamine-induced apoptosis in an immortalized neural cell line by suppressing the production of reactive oxygen species.  Synapse. 2000;  35 228-233
  • 28 Kirkland R A, Windelborn J A, Kasprzak J M, Franklin J L. A Bax induced pro-oxidant state is critical for cytochrome c release during programmed neuronal death.  J Neurosci. 2002;  22 6480-6490
  • 29 Morissette M C, Vachon-Beaudoin G, Parent J, Chakir J, Milot J. Increased p 53 level, Bax/Bcl-x(L) ratio, and TRAIL receptor expression in human emphysema.  Am J Respir Crit Care Med. 2008;  178 240-247
  • 30 Cheng X R, Zhang L, Hu J J, Sun L, Du G H. Neuroprotective effects of tetramethylpyrazine on hydrogen peroxide-induced apoptosis in PC12 cells.  Cell Biol Int. 2007;  31 438-443

Professor Xiaoxiang Zheng

Department of Biomedical Engineering
Key Laboratory of Biomedical Engineering
Ministry of Education
Zhejiang University

Zheda Road 38

310027 Hang Zhou

People's Republic of China

Phone: + 86 5 71 87 95 38 60

Fax: + 86 5 71 87 95 16 76

Email: zxx@mail.bme.zju.edu.cn

    >