Journal List > Nat Prod Sci > v.22(3) > 1060616

TOOLS
Shin, Zhao, Park, Kim, Choi, and Lee: Effects of Gypenosides on Dopaminergic Neuronal Cell Death in 6-Hydroxydopamine-lesioned Rat Model of Parkinson's Disease with Longterm L-DOPA Treatment
Original Article

Natural Product Sciences 2016;22(3):187-192.

Published online: 17 January 2016

DOI: https://doi.org/10.20307/nps.2016.22.3.187

Effects of Gypenosides on Dopaminergic Neuronal Cell Death in 6-Hydroxydopamine-lesioned Rat Model of Parkinson's Disease with Longterm L-DOPA Treatment

Keon Sung Shin1, Ting Ting Zhao1, Hyun Jin Park1, Kyung Sook Kim1, Hyun Sook Choi2, Myung Koo Lee1, ∗

1College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Chungbuk 28644, Korea

2Department of Food and Nutrition, Chungcheong University, 38, Wuelgok-gil, Cheongju, Chungbuk 28171, Korea

∗Author for correspondence Myung Koo Lee, College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. Tel: +82-43-261-2822; E-mail: myklee@chungbuk.ac.kr

Received 28 January 2016       Revised 29 February 2016       Accepted 29 February 2016

Copyright © 2016 The Korean Society of Pharmacognosy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The goal of this study was to determine whether gypenosides (GPS) exert protective effects against dopaminergic neuronal cell death in a 6-hydroxydopamine (OHDA)-lesioned rat model of Parkinson's disease (PD) with or without longterm 3,4-dihydroxyphenylalanine (L-DOPA) treatment. Rats were injected with 6-OHDA in the substantia nigra to induce PD-like symptoms; 14 days after injection, groups of 6-OHDA-lesioned animals were treated for 21 days with GPS (25 or 50 mg/kg) and/or L-DOPA (20 mg/kg). Dopaminergic neuronal cell death was assessed by counting tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra and measuring levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. Dopaminergic neuronal cell death induced by 6-OHDA lesions was ameliorated by GPS treatment (50mg/kg). L-DOPA treatment exacerbated 6-OHDA-induced dopaminergic neuronal cell death; however, these effects were partially reversed by GPS treatment (25 and 50 mg/kg). These results suggest that GPS treatment is protective against dopaminergic neuronal cell death in a 6-OHDA-lesioned rat model of PD with longterm L-DOPA treatment. Therefore, GPS may be useful as a phytotherapeutic agent for the treatment of PD.

Keywords: Gypenosides, 6-Hydroxydopamine-lesioned rat, Parkinson's disease, Tyrosine hydroxylase immuno-histochemistry, L-DOPA

REFERENCES

(1). Fearnley J. M., Lees A. J.Brain. 1991; 114:2283–2301.
(2). Fahn S. Ann. N. Y.Acad. Sci. 2003; 991:1–14.
(3). Marsden C. D. J.Neurol. Neurosurg. Psychiatry. 1994; 57:672–681.
(4). Jankovic J.Mov. Disord. 2005; 20:S11–S16.
(5). Cheng N., Maeda T., Kume T., Kaneko S., Kochiyama H., Akaike A., Goshima Y., Misu Y.Brain Res. 1996; 16:278–283.
(6). Walkinshaw G., Waters C. M. J.Clin. Invest. 1995; 95:2458–2464.
(7). Shin K. S., Zhao T. T., Park K. H., Park H. J., Hwang B. Y., Lee C. K., Lee M. K.BMC Neurosci. 2015; 16:23.
(8). Bové J., Perier C.Neuroscience. 2012; 211:51–76.
(9). Jackson-Lewis V., Blesa J., Przedborski S.Parkinsonism Relat. Disord. 2012; 18:S183–S185.
(10). Seidl S. E., Potashkin J. A.Front. Neurol. 2011; 2:68.
(11). Razmovski-Naumovski V., Huang T. H. W., Tran V. H., Li G. Q., Duke C. C., Roufogalis B. D.Phytochem. Rev. 2005; 4:197–219.
(12). Im S. A., Choi H. S., Hwang B. Y., Lee M. K., Lee C.K.Kor. J. Pharmacogn. 2009; 40:35–40.
(13). Choi H. S., Zhao T. T., Shin K. S., Kim S. H., Hwang B. Y., Lee C. K., Lee M. K.Molecules. 2013; 18:4342–4356.
(14). Choi H. S., Park M. S., Kim S. H., Hwang B. Y., Lee C. K., Lee M. K.Molecules. 2010; 15:2814–2824.
(15). Shang L. S., Liu J. C., Zhu Q. J., Zhao L., Feng Y., Wang X., Cao W., Xin H.Brain Res. 2006; 1102:163–174.
(16). Wang P., Niu L., Guo X. D., Gao L., Li W. X., Jia D., Wang X. L, Ma L. T., Gao G. D.Brain Res. Bull. 2010; 83:266–271.
(17). Zhang G., Zhao Z., Gao L., Deng J., Wang B., Xu D., Liu B., Qu Y., Yu J., Li J., Gao G.Pharmacol. Biochem. Behav. 2011; 99:42–51.
(18). Wang P., Niu L., Gao L., Li W. X., Jia D., Wang X. L., Gao G. D. J.Int. Med. Res. 2010; 38:1084–1092.
(19). Paxinos G., Watson C.The rat brain in stereotaxic coordinates. 2nd ed. Academic Press;Australia: 1986.
(20). Schwarting R. K. W., Huston J. P.Prog. Neurobiol. 1996; 50:275–331.
(21). Mo J., Zhang H., Yu L. P., Sun P. H., Jin G. Z., Zhen X.Neurobiol. Aging. 2010; 31:926–936.
(22). Izurieta-Sánchez P., Sarre S., Ebinger G., Michotte Y.Eur. J. Pharmacol. 1998; 353:33–42.
(23). Ljungberg T., Ungerstedt U.Eur. J. Pharmacol. 1977; 46:147–151.
(24). Blesa J., Phani S., Jackson-Lewis V., Przedborski S. J.BioMed. Biotechnol. 2012; 2012:845618.
(25). Shin K. S., Zhao T. T., Choi H. S., Hwang B. Y., Lee C. K., Lee M. K.Brain Res. 2014; 1567:57–65.
(26). Cenci M. A.Parkinsonism Relat. Disord. 2007; 13:S263–S267.
(27). Cohen G.Neurotoxicology. 1984; 5:77–82.
(28). Soto-Otero R., Méndez-Álvarez E., Hermida-Ameijeiras Á., Muñoz-Patiño A. M., Labandeira-Garcia J. L. J.Neurochem. 2000; 74:1605–1612.
(29). Cadet J. L., Brannock C.Neurochem. Int. 1998; 32:117–131.
(30). Fahn S., Cohen G.Ann. Neurol. 1992; 32:804–812. 2004.
(31). Schober A.Cell Tissue Res. 2004; 318:215–224.
(32). Blandini F., Armentero M. T., Martignoni E.Parkinsonism Relat. Disord. 2008; 14:S124–S129.
(33). Severson J. A., Marcusson J., Winblad B., Finch C. E. J.Neurochem. 1982; 39:1623–1631.
(34). Linert W., Herlinger E., Jameson R. F., Kienzl E., Jellinger K., Youdim M. B.Biochim. Biophys. Acta. 1996; 1316:160–168.
(35). Maharaj H., Sukhdev Maharaj D., Scheepers M., Mokokong R., Daya S.Brain Res. 2005; 1063:180–186.
(36). Basma A. N., Morris E. J., Nicklas W. J., Geller H. M. J.Neurochem. 1995; 64:825–832.
(37). Migheli R., Godani C., Sciola L., Delogu M. R., Serra P. A., Zangani D., De Natale G., Miele E., Desole M. S. J.Neurochem. 1999; 73:1155–1163.
(38). Zhang L., Dawson V. L., Dawson T. M.Pharmacol. Ther. 2006; 109:33–41.
(39). Padovan-Neto F. E., Echeverry M. B., Tumas V., Del-Bel E. A.Neuroscience. 2009; 159:927–935.
(40). Nicklas W. J., Vyas I., Heikkila R. E.Life Sci. 1985; 36:2503–2508.
(41). Yacoubian T. A., Standaert D. G.Biochim. Biophys. Acta. 2009; 1792:676–687.
(42). Cai T. S., Zhang S. F., Wang M. C.Chin. J. Clin. Rehabil. 2005; 9:106–107.
(43). Tanner M. A., Bu X., Steimle J. A., Myers P. R.Nitric Oxide. 1999; 3:359–365.

Fig. 1.
Representative photomicrographs of tyrosine hydroxylase (TH) immunoreactivity (A) and numbers of surviving TH-immu-nopositive cells (B) in the substantia nigra. Fourteen days after lesions were induced by 6-hydroxydopamine (6-OHDA) injection into the substantia nigra, rats were treated for 21 days with gypenosides (GPS) and/or a combination of L-DOPA (LD) and benserazide. (A) Arrows indicate 6-OHDA-lesioned areas. Scale bar = 100 µm. (B) Numbers of TH-immunopositive cells on the lesioned side (L) were analyzed as a percentage of the intact side (R). Results are presented as mean ± S.E.M.; n = 8 – 10 animals per group.∗P <0.05 compared with control group;#P <0.05 compared with 6-OHDA-lesioned group; §P < 0.05 compared with 6-OHDA-lesioned group treated with L-DOPA alone.
nps-22-187f1.tif
Fig. 2.
Effects of GPS on striatal dopamine levels on the intact (R) and 6-OHDA-lesioned (L) sides. Following 6-OHDA lesion and L-DOPA and/or GPS treatment, levels of dopamine in the striatum were determined using HPLC. Numbers in parentheses represent dopamine levels expressed as percentages of the control group (L). Results are presented as mean ± S.E.M.; n = 8 – 10 animals per group.∗P < 0.05 compared with control group;#P <0.05 compared with 6-OHDA-lesioned group; §P <0.05 compared with 6-OHDA-lesioned group treated with L-DOPA alone.
nps-22-187f2.tif
Fig. 3.
Effects of GPS on striatal norepinephrine levels on the intact (R) and 6-OHDA-lesioned (L) sides. Numbers in parentheses represent norepinephrine levels expressed as percentages of the control group (L). Results are presented as mean ± S.E.M.; n =8–10 animals per group.∗P <0.05 compared with control group;#P < 0.05 compared with 6-OHDA-lesioned group;§P < 0.05 compared with 6-OHDA-lesioned group treated with L-DOPA alone.
nps-22-187f3.tif
Fig. 4.
Effects of GPS on striatal 3,4-dihydroxyphenylacetic acid (DOPAC) levels on the intact (R) and 6-OHDA-lesioned (L) sides. Numbers in parentheses represent DOPAC levels expressed as percentages of the control group (L). Results are presented as mean ± S.E.M.; n=8–10 animals per group.∗P <0.05 compared with control group;#P < 0.05 compared with 6-OHDA-lesioned group;§P < 0.05 compared with 6-OHDA-lesioned group treated with L-DOPA alone.
nps-22-187f4.tif
Fig. 5.
Effects of GPS on striatal homovanillic acid (HVA) levels on the intact (R) and 6-OHDA-lesioned (L) sides. Numbers in parentheses represent HVA levels expressed as percentages of the control group (L). Results are presented as mean ± S.E.M.; n=8–10 animals per group.∗P < 0.05 compared with control group; #P < 0.05 compared with 6-OHDA-lesioned group; §P < 0.05 compared with 6-OHDA-lesioned group treated with L-DOPA alone.
nps-22-187f5.tif
TOOLS
Similar articles