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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway

Authors: Ji-Hyun Park, Young Ho Seo, Jung-Hee Jang, Chul-Ho Jeong, Sooyeun Lee, Byoungduck Park

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Methamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway.

Methods

We used the human dopaminergic neuroblastoma SH-SY5Y cell line, murine microglial BV2 cell line, and primary culture of rat embryo mesencephalic neurons. Pro-inflammatory cytokine production was monitored by ELISA and RT/real-time PCR. The cell cycle distribution and mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting, DNA-binding activity, and immunofluorescence staining to analyze the effect of AA on activation of the NF-κB, STAT3, MAPK-ERK, and apoptosis signaling pathways.

Results

METH induced TNF receptor (TNFR) expression and led to morphological changes of cells. Additionally, this drug increased pro-inflammatory cytokine (TNFα and IL-6) expression. AA significantly suppressed METH-induced TNFR expression in concentration dependent. Increased secretion of TNFα and IL-6 was inhibited in METH-stimulated neuronal cells by AA administration. AA showed significant protection against METH-induced translocation of NF-κB/STAT3 and ERK phosphorylation. AA inhibited METH-induced proteolytic fragmentation of caspase-3 and PARP. The pro-apoptotic protein Bax was significantly decreased, while the anti-apoptotic protein Bcl-xL was increased by AA treatment in METH-stimulated cells. A similar protective effect of AA on mitochondrial membrane integrity was also confirmed by flow cytometry and immunofluorescence staining.

Conclusions

Based on the literatures and our findings, AA is a promising candidate for an anti-neurotoxic agent, and it can potentially be used for the prevention and treatment of various neurological disorders.
Appendix
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Literature
1.
Goncalves J, Baptista S, Martins T, Milhazes N, Borges F, Ribeiro CF, Malva JO, Silva AP. Methamphetamine-induced neuroinflammation and neuronal dysfunction in the mice hippocampus: preventive effect of indomethacin. Eur J Neurosci. 2010;31:315–26.CrossRefPubMed
2.
Jumnongprakhon P, Govitrapong P, Tocharus C, Tungkum W, Tocharus J. Protective effect of melatonin on methamphetamine-induced apoptosis in glioma cell line. Neurotox Res. 2014;25:286–94.CrossRefPubMed
3.
Shin EJ, Shin SW, Nguyen TT, Park DH, Wie MB, Jang CG, Nah SY, Yang BW, Ko SK, Nabeshima T, Kim HC. Ginsenoside Re rescues methamphetamine-induced oxidative damage, mitochondrial dysfunction, microglial activation, and dopaminergic degeneration by inhibiting the protein kinase Cdelta gene. Mol Neurobiol. 2014;49:1400–21.CrossRefPubMed
4.
Morrow BA, Roth RH, Redmond DE, Elsworth JD. Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson’s disease. Neuroscience. 2011;189:277–85.CrossRefPubMedPubMedCentral
5.
Nguyen XK, Lee J, Shin EJ, Dang DK, Jeong JH, Nguyen TT, Nam Y, Cho HJ, Lee JC, Park DH, et al. Liposomal melatonin rescues methamphetamine-elicited mitochondrial burdens, pro-apoptosis, and dopaminergic degeneration through the inhibition PKCdelta gene. J Pineal Res. 2015;58:86–106.CrossRefPubMed
6.
Wen D, An M, Gou H, Liu X, Liu L, Ma C, Cong B. Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway. Neurotoxicology. 2016;57:31-38.
7.
Dang DK, Shin EJ, Nam Y, Ryoo S, Jeong JH, Jang CG, Nabeshima T, Hong JS, Kim HC. Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK. J Neuroinflammation. 2016;13:12.CrossRefPubMedPubMedCentral
8.
Reiner DJ, Yu SJ, Shen H, He Y, Bae E, Wang Y. 9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons. Neurotox Res. 2014;25:248–61.CrossRefPubMed
9.
Coelho-Santos V, Goncalves J, Fontes-Ribeiro C, Silva AP. Prevention of methamphetamine-induced microglial cell death by TNF-alpha and IL-6 through activation of the JAK-STAT pathway. J Neuroinflammation. 2012;9:103.CrossRefPubMedPubMedCentral
10.
Wang Q, Shin EJ, Nguyen XK, Li Q, Bach JH, Bing G, Kim WK, Kim HC, Hong JS. Endogenous dynorphin protects against neurotoxin-elicited nigrostriatal dopaminergic neuron damage and motor deficits in mice. J Neuroinflammation. 2012;9:124.PubMedPubMedCentral
11.
Nam Y, Wie MB, Shin EJ, Nguyen TT, Nah SY, Ko SK, Jeong JH, Jang CG, Kim HC. Ginsenoside Re protects methamphetamine-induced mitochondrial burdens and proapoptosis via genetic inhibition of protein kinase C delta in human neuroblastoma dopaminergic SH-SY5Y cell lines. J Appl Toxicol. 2015;35:927–44.CrossRefPubMed
12.
Ajjimaporn A, Shavali S, Ebadi M, Govitrapong P. Zinc rescues dopaminergic SK-N-SH cell lines from methamphetamine-induced toxicity. Brain Res Bull. 2008;77:361–6.CrossRefPubMed
13.
Klongpanichapak S, Phansuwan-Pujito P, Ebadi M, Govitrapong P. Melatonin inhibits amphetamine-induced increase in alpha-synuclein and decrease in phosphorylated tyrosine hydroxylase in SK-N-SH cells. Neurosci Lett. 2008;436:309–13.CrossRefPubMed
14.
Shah A, Silverstein PS, Singh DP, Kumar A. Involvement of metabotropic glutamate receptor 5, AKT/PI3K signaling and NF-kappaB pathway in methamphetamine-mediated increase in IL-6 and IL-8 expression in astrocytes. J Neuroinflammation. 2012;9:52.CrossRefPubMedPubMedCentral
15.
Permpoonputtana K, Govitrapong P. The anti-inflammatory effect of melatonin on methamphetamine-induced proinflammatory mediators in human neuroblastoma dopamine SH-SY5Y cell lines. Neurotox Res. 2013;23:189–99.CrossRefPubMed
16.
Venkatesan R, Ji E, Kim SY. Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: a comprehensive review. Biomed Res Int. 2015;2015:814068.CrossRefPubMedPubMedCentral
17.
Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 1813;2011:878–88.
18.
Wang K, Xie M, Zhu L, Zhu X, Zhang K, Zhou F. Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Abeta1-42-induced neurotoxicity via activating the JAK2/STAT3 axis. Folia Neuropathol. 2015;53:226–35.CrossRefPubMed
19.
Cadet JL, Jayanthi S, Deng X. Methamphetamine-induced neuronal apoptosis involves the activation of multiple death pathways. Review. Neurotox Res. 2005;8:199–206.CrossRefPubMed
20.
Beauvais G, Atwell K, Jayanthi S, Ladenheim B, Cadet JL. Involvement of dopamine receptors in binge methamphetamine-induced activation of endoplasmic reticulum and mitochondrial stress pathways. PLoS One. 2011;6:e28946.CrossRefPubMedPubMedCentral
21.
Wang SF, Yen JC, Yin PH, Chi CW, Lee HC. Involvement of oxidative stress-activated JNK signaling in the methamphetamine-induced cell death of human SH-SY5Y cells. Toxicology. 2008;246:234–41.CrossRefPubMed
22.
Xing B, Xin T, Zhao L, Hunter RL, Chen Y, Bing G. Glial cell line-derived neurotrophic factor protects midbrain dopaminergic neurons against lipopolysaccharide neurotoxicity. J Neuroimmunol. 2010;225:43–51.CrossRefPubMedPubMedCentral
23.
Tsao SM, Yin MC. Antioxidative and antiinflammatory activities of asiatic acid, glycyrrhizic acid, and oleanolic acid in human bronchial epithelial cells. J Agric Food Chem. 2015;63:3196–204.CrossRefPubMed
24.
25.
Nataraj J, Manivasagam T, Justin Thenmozhi A, Essa MM. Neuroprotective effect of asiatic acid on rotenone-induced mitochondrial dysfunction and oxidative stress-mediated apoptosis in differentiated SH-SYS5Y cells. Nutr Neurosci. 2017;20:351–9.CrossRefPubMed
26.
Jiang W, Li M, He F, Bian Z, He Q, Wang X, Yao W, Zhu L. Neuroprotective effect of asiatic acid against spinal cord injury in rats. Life Sci. 2016;157:45–51.CrossRefPubMed
27.
Xu MF, Xiong YY, Liu JK, Qian JJ, Zhu L, Gao J. Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells. Acta Pharmacol Sin. 2012;33:578–87.CrossRefPubMedPubMedCentral
28.
Sirichoat A, Chaijaroonkhanarak W, Prachaney P, Pannangrong W, Leksomboon R, Chaichun A, Wigmore P, Welbat JU. Effects of asiatic acid on spatial working memory and cell proliferation in the adult rat hippocampus. Nutrients. 2015;7:8413–23.CrossRefPubMedPubMedCentral
29.
Krishnamurthy RG, Senut MC, Zemke D, Min J, Frenkel MB, Greenberg EJ, Yu SW, Ahn N, Goudreau J, Kassab M, et al. Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia. J Neurosci Res. 2009;87:2541–50.CrossRefPubMedPubMedCentral
30.
Umka Welbat J, Sirichoat A, Chaijaroonkhanarak W, Prachaney P, Pannangrong W, Pakdeechote P, Sripanidkulchai B, Wigmore P. Asiatic acid prevents the deleterious effects of valproic acid on cognition and hippocampal cell proliferation and survival. Nutrients. 2016;8:303.CrossRefPubMedCentral
31.
Pruszak J, Just L, Isacson O, Nikkhah G: Isolation and culture of ventral mesencephalic precursor cells and dopaminergic neurons from rodent brains. Curr Protoc Stem Cell Biol 2009, Chapter 2:Unit 2D.5. doi:10.​1002/​9780470151808.​sc02d05s11.
32.
Park JH, Lee MK, Yoon J. Gamma-linolenic acid inhibits hepatic PAI-1 expression by inhibiting p38 MAPK-dependent activator protein and mitochondria-mediated apoptosis pathway. Apoptosis. 2015;20:336–47.CrossRefPubMed
33.
Park JH, Lee KY, Park B, Yoon J. Suppression of Th2 chemokines by crocin via blocking of ERK-MAPK/NF-kappaB/STAT1 signalling pathways in TNF-alpha/IFN-gamma-stimulated human epidermal keratinocytes. Exp Dermatol. 2015;24:634–6.CrossRefPubMed
34.
Carniglia L, Ramirez D, Durand D, Saba J, Turati J, Caruso C, Scimonelli TN, Lasaga M. Neuropeptides and microglial activation in inflammation, pain, and neurodegenerative diseases. Mediat Inflamm. 2017;2017:5048616.CrossRef
35.
36.
McArthur S, Cristante E, Paterno M, Christian H, Roncaroli F, Gillies GE, Solito E. Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia. J Immunol. 2010;185:6317–28.CrossRefPubMedPubMedCentral
37.
Skaper SD, Mercanti G, Facci L. Culture and characterization of rat mesencephalic dopaminergic neurons. Methods Mol Biol. 2012;846:91–101.CrossRefPubMed
38.
Shin EJ, Dang DK, Tran TV, Tran HQ, Jeong JH, Nah SY, Jang CG, Yamada K, Nabeshima T, Kim HC. Current understanding of methamphetamine-associated dopaminergic neurodegeneration and psychotoxic behaviors. Arch Pharm Res. 2017;40:403–28.CrossRefPubMed
39.
Robson MJ, Turner RC, Naser ZJ, McCurdy CR, O'Callaghan JP, Huber JD, Matsumoto RR. SN79, a sigma receptor antagonist, attenuates methamphetamine-induced astrogliosis through a blockade of OSMR/gp130 signaling and STAT3 phosphorylation. Exp Neurol. 2014;254:180–9.CrossRefPubMedPubMedCentral
40.
Wang X, Wang C, Wang J, Zhao S, Zhang K, Wang J, Zhang W, Wu C, Yang J. Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-kappaB, MAPKs and Akt signaling pathways. Neuropharmacology. 2014;79:642–56.CrossRefPubMed
41.
Yan T, Li L, Sun B, Liu F, Yang P, Chen T, Li T, Liu X. Luteolin inhibits behavioral sensitization by blocking methamphetamine-induced MAPK pathway activation in the caudate putamen in mice. PLoS One. 2014;9:e98981.CrossRefPubMedPubMedCentral
42.
Nair MP, Saiyed ZM, Nair N, Gandhi NH, Rodriguez JW, Boukli N, Provencio-Vasquez E, Malow RM, Miguez-Burbano MJ. Methamphetamine enhances HIV-1 infectivity in monocyte derived dendritic cells. J NeuroImmune Pharmacol. 2009;4:129–39.CrossRefPubMed
43.
Shiflett MW, Balleine BW. Contributions of ERK signaling in the striatum to instrumental learning and performance. Behav Brain Res. 2011;218:240–7.CrossRefPubMed
44.
Nestler EJ. Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci. 2001;2:119–28.CrossRefPubMed
45.
Mizoguchi H, Yamada K, Mizuno M, Mizuno T, Nitta A, Noda Y, Nabeshima T. Regulations of methamphetamine reward by extracellular signal-regulated kinase 1/2/ets-like gene-1 signaling pathway via the activation of dopamine receptors. Mol Pharmacol. 2004;65:1293–301.CrossRefPubMed
46.
Matsumoto RR, Nguyen L, Kaushal N, Robson MJ. Sigma (sigma) receptors as potential therapeutic targets to mitigate psychostimulant effects. Adv Pharmacol. 2014;69:323–86.CrossRefPubMed
47.
Huang YN, Yang LY, Wang JY, Lai CC, Chiu CT, Wang JY. L-Ascorbate protects against methamphetamine-induced neurotoxicity of cortical cells via inhibiting oxidative stress, autophagy, and apoptosis. Mol Neurobiol. 2017;54:125–36.CrossRefPubMed
48.
Shin EJ, Duong CX, Nguyen XK, Li Z, Bing G, Bach JH, Park DH, Nakayama K, Ali SF, Kanthasamy AG, et al. Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cdelta. Behav Brain Res. 2012;232:98–113.CrossRefPubMedPubMedCentral
Metadata
Title
Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway
Authors
Ji-Hyun Park
Young Ho Seo
Jung-Hee Jang
Chul-Ho Jeong
Sooyeun Lee
Byoungduck Park
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-1009-0

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