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Tormentic acid confers protection against oxidative stress injury in rats with Parkinson's disease by targeting the Wnt/β-catenin signaling pathway
Corresponding Author(s) : Xiaohua Jiang
Cellular and Molecular Biology,
Vol. 66 No. 1: Issue 1
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Studies have shown that oxidative stress (OS) may contribute to the cascade of reactions leading to the degeneration of dopaminergic neurons in the brain. The present study investigated the protective effect of tormentic acid (TMA) on OS-induced injury in rat model of PD, and the underlying mechanism. Evaluation of learning and memorizing ability was done using Morris water maze (MWM) test. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and level of malondialdehyde (MDA) in substantia nigra were determined using enzyme-linked immunosorbent assay (ELISA). The protein and mRNA expressions of β-catenin, GSK-3β, and GSK-3β-Ser9 were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting. The effect of TA on cell viability and proliferation was determined in vitro on rat adrenal pheochromocytoma (PC12) cell line using MTT assay. The results showed that the escape latency of rats in negative control group was significantly higher than that in normal control group (p < 0.05). However, treatment with TMA significantly and time-dependently reduced the escape latency of the rats (p < 0.05). The extent of apoptosis was significantly reduced after treatment with TMA (p < 0.05). Besides, treatment with TMA significantly increased the viability of brain cells (p < 0.05). The activities of SOD and GPx were significantly lower in negative control group than in normal control group, but were significantly increased after treatment with TMA (p < 0.05). The level of MDA was significantly higher in negative control group than in normal control group, but was significantly reduced after treatment with TMA (p < 0.05). The results of qRT-PCR and Western blotting showed that treatment with TMA significantly activated Wnt/β-catenin signaling pathway (p < 0.05). TMA treatment significantly reversed the effect of 6-hydroxydopamine on the expression levels of these proteins and their mRNAs (p < 0.05). These results suggest that TMA confers protection against OS-induced injury in rats with PD by targeting the Wnt/β-catenin signaling pathway.
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- Nishijima H, Tomiyama M. What mechanisms are responsible for the reuptake of levodopa-derived dopamine in parkinsonian striatum? Front Neurosci 2016; 10: 575.
- Vander-Merwe C, Van-Dyk HC, Engelbrecht L, Vander-Westhuizen FH, Kinnear C, Loos B, et al. Curcumin rescues a PINK1 knock down SH-SY5Y cellular model of Parkinson's disease from mitochondrial dysfunction and cell death. Mol Neurobiol 2017; 54: 2752-2762.
- Svenningsson P, Westman E, Ballard C, Aarsland D. Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment. Lancet Neurol 2012; 11: 697-707.
- Pagano G, Niccolini F, Fusar-Poli P, Politis M. Serotonin transporter in Parkinson's disease: A meta"analysis of positron emission tomography studies. Ann Neurol 2017; 81: 171-180.
- Chi J, Xie Q, Jia J, Liu X, Sun J, Deng Y, et al. Integrated analysis and identification of novel biomarkers in Parkinson's disease. Front Aging Neurosci 2018; 10: 178.
- Kalia SK, Kalia LV, McLean PJ. Molecular chaperones as rational drug targets for Parkinson's disease therapeutics. CNS Neurol Disord Drug Targets 2010; 9: 741-753.
- Romuk EB, Szczurek W, Nowak PG, Hudziec E, Chwalińska E, Birkner E. Effects of Propofol on the Liver Oxidative-Antioxidant Balance in a Rat Model of Parkinson's Disease. Adv Clin Exp Med 2016; 25: 815-820.
- Sita G, Hrelia P, Tarozzi A, Morroni F. Isothiocyanates are promising compounds against oxidative stress, neuroinflammation and cell death that may benefit neurodegeneration in Parkinson's disease. Int J Mol Sci 2016; 17: 1454.
- Cho EJ, Yokozawa T, Rhyu DY, Kim HY, Shibahara N. The inhibitory effects of 12 medicinal plants and their component compounds on lipid peroxidation. Am J Chin Med 2003; 31: 907-917.
- Lin X, Zhang S, Huang R, Tan S, Liang S, Wu X, et al. Protective effect of tormentic acid from Potentilla chinensis against lipopolysaccharide/D-galactosamine induced fulminant hepatic failure in mice. Int Immunopharmacol 2014; 19: 365-372.
- Gao H, Wu L, Kuroyanagi M, Harada K, Kawahara N, Nakane T, et al. Antitumor-promoting constituents from Chaenomeles sinensis Koehne and their activities in JB6 mouse epidermal cells. Chem Pharm Bull (Tokyo) 2003; 51: 1318-1321.
- Wu JB, Kuo YH, Lin CH, Ho HY, Shih CC. Tormentic acid, a major component of suspension cells of Eriobotrya japonica, suppresses high-fat diet-induced diabetes and hyperlipidemia by glucose transporter 4 and AMP-activated protein kinase phosphorylation. J Agric Food Chem 2014; 62: 10717-10726.
- Jacob R, Nalini G, Chidambaranathan N. Neuroprotective effect of Rhodiola rosea Linn against MPTP induced cognitive impairment and oxidative stress. Ann Neurosci 2013; 20: 47.
- Bae ON, Serfozo K, Baek SH, Lee KY, Dorrance A, Rumbeiha W, et al. Safety and efficacy evaluation of carnosine, an endogenous neuroprotective agent for ischemic stroke. Stroke 2013; 44: 205-212.
- Varçin M, Bentea E, Michotte Y, Sarre S. Oxidative stress in genetic mouse models of Parkinson's disease. Oxid. Med. Cell Longev 2012; 2012: 624925.
- Hwang O. Role of oxidative stress in Parkinson's disease. J Endourol 2013; 22: 11-17.
- Zhou C, Huang Y, Przedborski S. Oxidative stress in Parkinson's disease: a mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci 2008; 1147: 93-104.
- Boonen RA, Van-Tijn P, Zivkovic D. Wnt signaling in Alzheimer's disease: up or down, that is the question. Ageing Res Rev 2009; 8: 71-82.
- Vargas JY, Ahumada J, Arrázola MS, Fuenzalida M. WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers. Exp Neurol 2015; 264: 14-25.
- Zhang L, Bahety P, Ee PLR. Wnt co-receptor LRP5/6 overexpression confers protection against hydrogen peroxide-induced neurotoxicity and reduces tau phosphorylation in SH-SY5Y cells. Neurochem Int 2015; 87: 13-21.
- Zhang J, Graham DG, Montine TJ, Ho YS. Enhanced N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine toxicity in mice deficient in CuZn-superoxide dismutase or glutathione peroxidase. Neurology 2000; 59: 53-61.
- Eriksen JL, Dawson TM, Dickson DW, Petrucelli L. Caught in the act: α-synuclein is the culprit in Parkinson's disease. Neuron 2003; 40: 453-456.
- Olanow C. A radical hypothesis for neurodegeneration. Trends Neurosci 1993; 16: 439-444.
References
Nishijima H, Tomiyama M. What mechanisms are responsible for the reuptake of levodopa-derived dopamine in parkinsonian striatum? Front Neurosci 2016; 10: 575.
Vander-Merwe C, Van-Dyk HC, Engelbrecht L, Vander-Westhuizen FH, Kinnear C, Loos B, et al. Curcumin rescues a PINK1 knock down SH-SY5Y cellular model of Parkinson's disease from mitochondrial dysfunction and cell death. Mol Neurobiol 2017; 54: 2752-2762.
Svenningsson P, Westman E, Ballard C, Aarsland D. Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment. Lancet Neurol 2012; 11: 697-707.
Pagano G, Niccolini F, Fusar-Poli P, Politis M. Serotonin transporter in Parkinson's disease: A meta"analysis of positron emission tomography studies. Ann Neurol 2017; 81: 171-180.
Chi J, Xie Q, Jia J, Liu X, Sun J, Deng Y, et al. Integrated analysis and identification of novel biomarkers in Parkinson's disease. Front Aging Neurosci 2018; 10: 178.
Kalia SK, Kalia LV, McLean PJ. Molecular chaperones as rational drug targets for Parkinson's disease therapeutics. CNS Neurol Disord Drug Targets 2010; 9: 741-753.
Romuk EB, Szczurek W, Nowak PG, Hudziec E, Chwalińska E, Birkner E. Effects of Propofol on the Liver Oxidative-Antioxidant Balance in a Rat Model of Parkinson's Disease. Adv Clin Exp Med 2016; 25: 815-820.
Sita G, Hrelia P, Tarozzi A, Morroni F. Isothiocyanates are promising compounds against oxidative stress, neuroinflammation and cell death that may benefit neurodegeneration in Parkinson's disease. Int J Mol Sci 2016; 17: 1454.
Cho EJ, Yokozawa T, Rhyu DY, Kim HY, Shibahara N. The inhibitory effects of 12 medicinal plants and their component compounds on lipid peroxidation. Am J Chin Med 2003; 31: 907-917.
Lin X, Zhang S, Huang R, Tan S, Liang S, Wu X, et al. Protective effect of tormentic acid from Potentilla chinensis against lipopolysaccharide/D-galactosamine induced fulminant hepatic failure in mice. Int Immunopharmacol 2014; 19: 365-372.
Gao H, Wu L, Kuroyanagi M, Harada K, Kawahara N, Nakane T, et al. Antitumor-promoting constituents from Chaenomeles sinensis Koehne and their activities in JB6 mouse epidermal cells. Chem Pharm Bull (Tokyo) 2003; 51: 1318-1321.
Wu JB, Kuo YH, Lin CH, Ho HY, Shih CC. Tormentic acid, a major component of suspension cells of Eriobotrya japonica, suppresses high-fat diet-induced diabetes and hyperlipidemia by glucose transporter 4 and AMP-activated protein kinase phosphorylation. J Agric Food Chem 2014; 62: 10717-10726.
Jacob R, Nalini G, Chidambaranathan N. Neuroprotective effect of Rhodiola rosea Linn against MPTP induced cognitive impairment and oxidative stress. Ann Neurosci 2013; 20: 47.
Bae ON, Serfozo K, Baek SH, Lee KY, Dorrance A, Rumbeiha W, et al. Safety and efficacy evaluation of carnosine, an endogenous neuroprotective agent for ischemic stroke. Stroke 2013; 44: 205-212.
Varçin M, Bentea E, Michotte Y, Sarre S. Oxidative stress in genetic mouse models of Parkinson's disease. Oxid. Med. Cell Longev 2012; 2012: 624925.
Hwang O. Role of oxidative stress in Parkinson's disease. J Endourol 2013; 22: 11-17.
Zhou C, Huang Y, Przedborski S. Oxidative stress in Parkinson's disease: a mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci 2008; 1147: 93-104.
Boonen RA, Van-Tijn P, Zivkovic D. Wnt signaling in Alzheimer's disease: up or down, that is the question. Ageing Res Rev 2009; 8: 71-82.
Vargas JY, Ahumada J, Arrázola MS, Fuenzalida M. WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers. Exp Neurol 2015; 264: 14-25.
Zhang L, Bahety P, Ee PLR. Wnt co-receptor LRP5/6 overexpression confers protection against hydrogen peroxide-induced neurotoxicity and reduces tau phosphorylation in SH-SY5Y cells. Neurochem Int 2015; 87: 13-21.
Zhang J, Graham DG, Montine TJ, Ho YS. Enhanced N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine toxicity in mice deficient in CuZn-superoxide dismutase or glutathione peroxidase. Neurology 2000; 59: 53-61.
Eriksen JL, Dawson TM, Dickson DW, Petrucelli L. Caught in the act: α-synuclein is the culprit in Parkinson's disease. Neuron 2003; 40: 453-456.
Olanow C. A radical hypothesis for neurodegeneration. Trends Neurosci 1993; 16: 439-444.