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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

The Protective Effect of Korean Red Ginseng Against Rotenone-Induced Parkinson’s Disease in Rat Model: Modulation of Nuclear Factor-κβ and Caspase-3

Author(s): Mai A. Zaafan, Amr M. Abdelhamid and Sherine M. Ibrahim*

Volume 20, Issue 7, 2019

Page: [588 - 594] Pages: 7

DOI: 10.2174/1389201020666190611122747

Price: $65

Abstract

Objective: Korean red ginseng was reported to have many biological effects like the antioxidant and the anti-inflammatory activities. Oxidative stress and neuro-inflammation play major roles in the pathogenesis of Parkinson’s disease (PD). The current study aimed to investigate the protective effects of ginseng on rotenone-induced PD in rats.

Methods: Rats were randomly allocated into 4 groups: normal rats, rotenone control, ginseng+rotenone and ginseng only treated rats. The severity of PD was evaluated through locomotor activity perceived in the open field test, histological examination and immunohistochemical detection of amyloid-β in brain tissues, in addition to the biochemical assessment of tyrosine hydroxylase activity in brain tissues. Moreover, the following parameters were investigated for studying the possible mechanisms of ginseng neuroprotective effect: nuclear factor-κβ (NF-κβ), tumor necrosis factor-alpha (TNF-α), caspase- 3, lipid peroxides and reduced glutathione (GSH).

Results: Ginseng exhibited potent neuroprotective effect that was reflected upon the histopathological examination, marked improvement in the locomotor activity and through its ability to suppress the amyloid- β deposition in the cortex and striatum along with significant increase in the tyrosine hydroxylase activity. Ginseng successfully inhibited the NF-κβ inflammatory pathway in brain tissues beside the inhibition of other oxidative stress and inflammatory mediators. Furthermore, it exhibited antiapoptotic effect via the inhibition of caspase-3 expression.

Conclusion: Ginseng could be a promising treatment in PD. It can suppress dopaminergic neuron degeneration through variable mechanisms mainly via inhibition of NF-κβ pathway in addition to inhibition of oxidative stress and apoptosis.

Keywords: Ginseng, Parkinson's disease, anti-oxidant, nuclear factor-κβ, caspase-3, Rat model.

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[1]
Connolly, B.S.; Lang, A.E. Pharmacological treatment of Parkinson disease: A review. JAMA, 2014, 311(16), 1670-1683. [http://dx.doi.org/10.1001/jama.2014.3654]. [PMID: 24756517].
[2]
Wang, X.; Guan, Q.; Wang, M.; Yang, L.; Bai, J.; Yan, Z. Aging-related rotenone-induced neurochemical and behavioral deficits: role of SIRT2 and redox imbalance, and neuroprotection by AK-7. Drug Des. Devel. Ther., 2015, 9, 2553-2563.
[3]
Almeida, M.F.; Silva, C.M.; D’Unhao, A.M.; Ferrari, M.F. Aged Lewis rats exposed to low and moderate doses of rotenone are a good model for studying the process of protein aggregation and its effects upon central nervous system cell physiology. Arq. Neuropsiquiatr., 2016, 74(9), 737-744. [http://dx.doi.org/10.1590/0004-282X20160121]. [PMID: 27706423].
[4]
Lee, Y.M.; Yoon, H.; Park, H.M.; Song, B.C.; Yeum, K.J. Implications of red Panax ginseng in oxidative stress associated chronic diseases. J. Ginseng Res., 2017, 41(2), 113-119. [http://dx.doi.org/10.1016/j.jgr.2016.03.003]. [PMID: 28413314].
[5]
Radad, K.; Gille, G.; Moldzio, R.; Saito, H.; Rausch, W.D. Ginsenosides Rb1 and Rg1 effects on mesencephalic dopaminergic cells stressed with glutamate. Brain Res., 2004, 1021(1), 41-53. [http://dx.doi.org/10.1016/j.brainres.2004.06.030]. [PMID: 15328030].
[6]
Lin, W.M.; Zhang, Y.M.; Moldzio, R.; Rausch, W.D. Ginsenoside Rd attenuates neuroinflammation of dopaminergic cells in culture. J. Neural Transm. Suppl., 2007, 72, 105-112.
[7]
Hu, J.F.; Song, X.Y.; Chu, S.F.; Chen, J.; Ji, H.J.; Chen, X.Y. Inhibitory effect of ginsenoside Rg1 on lipopolysaccharide-induced microglial activation in mice. Brain Res., 2011, 16, 8-14. [http://dx.doi.org/10.1016/j.brainres.2010.11.069].
[8]
Ren, R.; Shi, C.; Cao, J.; Sun, Y.; Zhao, X.; Guo, Y. neuroprotective effects of a standardized flavonoid extract of safflower against neurotoxin-induced cellular and animal models of Parkinson’s disease. Scientif. Rep., 2016, 6, 22135. [http://dx.doi.org/10.1038/srep22135].
[9]
Lee, J.S.; Choi, H.S.; Kang, S.W.; Chung, J.H.; Park, H.K.; Ban, J.Y.; Kwon, O.Y.; Hong, H.P.; Ko, Y.G. Therapeutic effect of Korean red ginseng on inflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury. Am. J. Chin. Med., 2011, 39(1), 83-94. [http://dx.doi.org/10.1142/S0192415X1100866X]. [PMID: 21213400].
[10]
Ban, J.Y.; Kang, S.W.; Lee, J.S.; Chung, J.H.; Ko, Y.G.; Choi, H.S. Korean red ginseng protects against neuronal damage induced by transient focal ischemia in rats. Exp. Ther. Med., 2012, 3(4), 693-698. [http://dx.doi.org/10.3892/etm.2012.449]. [PMID: 22969953].
[11]
Banchroft, P.; Stevens, A.; Turner, D.R. Theory and practice of histological techniques. In: Churchil Livingstone, 4th ed; London. 1996.
[12]
Liu, M.; Xu, H.; Zhang, L.; Zhang, C.; Yang, L.; Ma, E.; Liu, L.; Li, Y. Salvianolic acid B inhibits myofibroblast trans differentiation in experimental pulmonary fibrosis via the up-regulation of Nrf2. Biochem. Biophys. Res. Commun., 2018, 495(1), 325-331. [http://dx.doi.org/10.1016/j.bbrc.2017.11.014]. [PMID: 29108993].
[13]
Tukey, J.W. Reminder sheets for “Discussion of paper on multiple comparisons by Henry Scheffe”. In the collected work of John W. Tukey VIII. Multiple comparisons; In: Chapman and Hall: New York, 1951.
[14]
Johnson, M.E.; Bobrovskaya, L. An update on the rotenone models of Parkinson’s disease: Their ability to reproduce the features of clinical disease and model gene-environment interactions. Neurotoxicology, 2015, 46(1), 101-116. [http://dx.doi.org/10.1016/j.neuro.2014.12.002]. [PMID: 25514659].
[15]
de Souza, M.F.; Bispo, J.M.M.; Leal, P.C.; de Gois, A.M.; Dos Santos, J.R. Commentary: Adenosine A2A receptor blockade prevents rotenone-induced motor impairment in a rat model of parkinsonism. Front. Behav. Neurosci., 2017, 11(93), 93. [http://dx.doi.org/10.3389/fnbeh.2017.00093]. [PMID: 28579949].
[16]
Maniyath, S.P.; Solaiappan, N.; Rathinasamy, M. Neurobehavioural changes in a hemiparkinsonian rat model induced by rotenone. J. Clin. Diagn. Res., 2017, 11(3), AF01-AF05. [http://dx.doi.org/10.7860/JCDR/2017/24955.9604]. [PMID: 28511367].
[17]
Kandil, E.A.; Abdelkader, N.F.; El-Sayeh, B.M.; Saleh, S. Imipramine and amitriptyline ameliorate the rotenone model of Parkinson’s disease in rats. Neuroscience, 2016, 332(1), 26-37. [http://dx.doi.org/10.1016/j.neuroscience.2016.06.040]. [PMID: 27365173].
[18]
Rastogi, V.; Santiago-Moreno, J.; Doré, S. Ginseng: A promising neuroprotective strategy in stroke. Front. Cell. Neurosci., 2015, 8(457), 457. [http://dx.doi.org/10.3389/fncel.2014.00457]. [PMID: 25653588].
[19]
Fernández-Moriano, C.; González-Burgos, E.; Iglesias, I.; Lozano, R.; Gómez-Serranillos, M.P. Evaluation of the adaptogenic potential exerted by ginsenosides Rb1 and Rg1 against oxidative stress-mediated neurotoxicity in an in vitro neuronal model. PLoS One, 2017, 12(8), e0182933. [http://dx.doi.org/10.1371/journal.pone.0182933]. [PMID: 28813475].
[20]
Thakur, P.; Nehru, B. Inhibition of neuroinflammation and mitochondrial dysfunctions by carbenoxolone in the rotenone model of Parkinson’s disease. Mol. Neurobiol., 2015, 51(1), 209-219. [http://dx.doi.org/10.1007/s12035-014-8769-7]. [PMID: 24946750].
[21]
Xu, W.; Zheng, D.; Liu, Y.; Li, J.; Yang, L.; Shang, X.; Glaucocalyxin, B. Alleviates Lipopolysaccharide-Induced Parkinson’s Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway. Cell. Physiol. Biochem., 2017, 44(6), 2091-2104. [http://dx.doi.org/10.1159/000485947]. [PMID: 29241205].
[22]
Anusha, C.; Sumathi, T.; Joseph, L.D. Protective role of apigenin on rotenone induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis. Chem. Biol. Interact., 2017, 269(1), 67-79. [http://dx.doi.org/10.1016/j.cbi.2017.03.016]. [PMID: 28389404].
[23]
Kim, K.H.; Lee, D.; Lee, H.L.; Kim, C.E.; Jung, K.; Kang, K.S. Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: past findings and future directions. J. Ginseng Res., 2018, 42(3), 239-247. [http://dx.doi.org/10.1016/j.jgr.2017.03.011]. [PMID: 29989012].
[24]
Cui, H.; Kong, Y.; Zhang, H. Oxidative stress, mitochondrial dysfunction, and aging. J. Signal Transduct., 2012, 2012(10), 646354. [PMID: 21977319].
[25]
Navarro-Yepes, J.; Zavala-Flores, L.; Anandhan, A.; Wang, F.; Skotak, M.; Chandra, N.; Li, M.; Pappa, A.; Martinez-Fong, D.; Del Razo, L.M.; Quintanilla-Vega, B.; Franco, R. Antioxidant gene therapy against neuronal cell death. Pharmacol. Ther., 2014, 142(2), 206-230. [http://dx.doi.org/10.1016/j.pharmthera.2013.12.007]. [PMID: 24333264].
[26]
Dexter, D.T.; Holley, A.E.; Flitter, W.D.; Slater, T.F.; Wells, F.R.; Daniel, S.E.; Lees, A.J.; Jenner, P.; Marsden, C.D. Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: An HPLC and ESR study. Mov. Disord., 1994, 9(1), 92-97. [http://dx.doi.org/10.1002/mds.870090115]. [PMID: 8139611].
[27]
Ojha, S.; Javed, H.; Azimullah, S.; Abul Khair, S.B.; Haque, M.E. Neuroprotective potential of ferulic acid in the rotenone model of Parkinson’s disease. Drug Des. Devel. Ther., 2015, 9(5), 5499-5510. [PMID: 26504373].
[28]
Anglade, P.; Vyas, S.; Javoy-Agid, F.; Herrero, M.T.; Michel, P.P.; Marquez, J.; Mouatt-Prigent, A.; Ruberg, M.; Hirsch, E.C.; Agid, Y. Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease. Histol. Histopathol., 1997, 12(1), 25-31. [PMID: 9046040].
[29]
Erekat, N.S.; Al-Jarrah, M.D. Association of Parkinson disease induction with cardiac upregulation of apoptotic mediators P53 and active caspase-3: An immunohistochemistry study. Med. Sci. Monit. Basic Res., 2018, 24(1), 120-126. [http://dx.doi.org/10.12659/MSMBR.910307]. [PMID: 30135418].
[30]
Liu, M.W.; Wei, R.; Su, M.X.; Li, H.; Fang, T.W.; Zhang, W. Effects of Panax notoginseng saponins on severe acute pancreatitis through the regulation of mTOR/Akt and caspase-3 signaling pathway by upregulating miR-181b expression in rats. BMC Complement. Altern. Med, 2018, 18(1), 018-2118.

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