Review Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: Future applications in Parkinson’s disease Abdelrahman Ibrahim Abushouk a,b,c , Ahmed Negida c,d,e , Hussien Ahmed c,d,e , Mohamed M. Abdel-Daim f, * a Faculty of Medicine, Ain Shams University, Cairo, Egypt b NovaMed Medical research Association, Cairo, Egypt c Medical Research Group of Egypt, Cairo, Egypt d Faculty of Medicine, Zagazig University, Zagazig, El-Sharkia, Egypt e Student Research Unit, Zagazig University, Zagazig, El-Sharkia, Egypt f Pharmacology department, Faculty of veterinary medicine, Suez Canal University, Ismailia, 41522, Egypt A R T I C L E I N F O Article history: Received 27 September 2016 Received in revised form 3 November 2016 Accepted 16 November 2016 Keywords: Parkinson’s disease Mptp Plant extracts Neuroprotection A B S T R A C T Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting about seven to 10 million patients worldwide. The major pathological features of PD are loss of dopaminergic neurons in the nigrostriatal pathway and accumulation of alpha-synuclein molecules, forming Lewy bodies. Until now, there is no effective cure for PD, and investigators are searching for neuroprotective strategies to stop or slow the disease progression. The MPTP (1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine) induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD in animal models. Multiple experimental studies showed the ability of several plant extracts to protect against MPTP induced neurotoxicity through activation of catalase, superoxide dismutase, and glutathione reductase enzymes, which reduce the cellular concentration of free radicals, preventing intracellular Ca ++ release and subsequent apoptosis signaling. Other neuroprotective mechanisms of plant extracts include promoting autophagy of alpha-synuclein molecules and exerting an antiapoptotic activity via inhibition of proteolytic poly (ADP-ribose) polymerase and preventing caspase cleavage. The variety of neuroprotective mechanisms of natural plant extracts may allow researchers to target PD progression in different pathological stages and may be through multiple pathways. Further investigations are required to translate these neuroprotective mechanisms into safe and effective treatments for PD. ã 2016 Elsevier Masson SAS. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2. Summary of neuroprotective effects of different plant extracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.1. Antioxidant activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.2. Antiapoptotic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.3. Autophagy enhancement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Abbreviations: ASK-1, Apoptosis signal regulating kinase-1; BDNF, Brain Derived Neurotrophic Factor; CI, Chrysanthemum indicum Linn; DAT, Dopamine transporter; EGb761, Ginkgo biloba extract 761; EGCG, Epigallocatechin-3-gallate; GR, Glutathione Reductase; H2O2, Hydrogen peroxide; HO-1, Heme-Oxygenase 1; JNK, c-Jun NH2- terminal kinase; LAMP-2A, Lysosome associated membrane protein type 2A; LC3-II, Light chain 3- phosphatidylethanolamine conjugate; MAPK, mitogen activated protein kinases; MDA, Malondialdehyde; MPTP, 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine; NADP(H)QO-1, Nicotine-Adenine Diphosphonucleotide, Quinone oxidoreductase 1 (NQO1); NBP, Dl-3-n-butylphthalide; NF-Kb, Nuclear factor- Kappa-B; NO, Nitric oxide; Nrf-2, Nuclear factor-2 Erythroid-2; PARP, Poly (ADP-ribose) polymerase; PC12, Pheochromocytoma cells 12; PCA, Protocatechuic acid; PF, Paeoniflorin; PGC, Peroxisome proliferator-activated receptor gamma coactivator 1; PI3K/Akt, Phosphatidylinositol 3-kinase/Protein Kinase B; ROS, Reactive oxygen species; SAC, S-Allylcysteine; SH-SY5Y, Human Neuroblastoma cells; SOD, Superoxide Dismutase; UPS, Ubiquitin Protease system. * Corresponding author. E-mail addresses: abdeldaim.m@vet.suez.edu.eg, abdeldaim.m@gmail.com (M.M. Abdel-Daim). http://dx.doi.org/10.1016/j.biopha.2016.11.074 0753-3322/ã 2016 Elsevier Masson SAS. All rights reserved. Biomedicine & Pharmacotherapy xxx (2016) xxx–xxx G Model BIOPHA 4584 No. of Pages 11 Please cite this article in press as: A.I. Abushouk, et al., Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: Future applications in Parkinson’s disease, Biomed Pharmacother (2016), http://dx.doi.org/10.1016/j.biopha.2016.11.074 Available online at ScienceDirect www.sciencedirect.com