Oxidative Stress and Parkinson's Disease: New Hopes in Treatment with Herbal Antioxidants
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See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/283728452 Oxidative stress and Parkinson's disease: New hopes in treatment with herbal antioxidants Article in Current pharmaceutical design · November 2015 CITATIONS READS 43 1,053 4 authors, including: Mahmoud Bahmani Hedayatollah Shirzad 219 PUBLICATIONS 2,021 CITATIONS Shahrekord University of Medical Sciences 106 PUBLICATIONS 1,357 CITATIONS SEE PROFILE SEE PROFILE Mahmoud Rafieian-kopaei Shahrekord University of Medical Sciences 337 PUBLICATIONS 5,110 CITATIONS SEE PROFILE Some of the authors of this publication are also working on these related projects: Genetic mapping of deafness in Iran View project expression of anti-oxidative stress genes in ulcerative colitis View project All content following this page was uploaded by Mahmoud Bahmani on 28 November 2015. provided by shahrekord university of medical scinces The user has requested enhancement of the downloaded file. View metadata, citation and similar papers at core.ac.uk CORE brought to you by Send Orders for Reprints to [email protected] Current Pharmaceutical Design, 2016, 22, 000-000 1 Oxidative Stress and Parkinson’s Disease: New Hopes in Treatment with Herbal Antioxidants Amir Sarrafchi1, Mahmoud Bahmani2, Hedayatollah Shirzad1 and Mahmoud Rafieian-Kopaei1* 1Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran; 2Food and Bev- erages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran Abstract: Parkinson's disease (PD) is a neurodegenerative disorder due to dopamine deficit in substatia nigra. PD is mainly a sporadic disease with unestablished etiology. However, exposure to environmental toxins, head trauma, Please provide corresponding author(s) inflammation, and free radicals are potential reasons. Recently, the role of oxidative stress in neurological abnor- photograph malities, including PD, has been particularly addressed. Antioxidant remedies, particularly herbal antioxidants, size should be 4" x 4" inches have revealed new perspectives of research and therapy as possible preventive and therapeutic approaches for PD. In this paper, we reviewed the recently published papers on the effects of herbal medicines on PD alongside the pathogenesis of PD with regard to oxidative stress. Keywords: Antioxidant, Degenerative disorder, Herbal medicines, Medicinal plants, Oxidative stress, Parkinson's disease. INTRODUCTION In fact, PD usually starts long before its manifestations appear. Parkinson’s disease (PD) is the second most common neurode- Therefore, the diets and medicinal plants with low side effects to generative disorder which is caused by reduction in dopamine level prevent them as well as knowledge of the first appearing biomark- and loss of projecting dopaminergic neurons in striatum and sub- ers and diagnostic methods to disguise the progressing disease at stantia nigra [1]. Dopaminergic impairment in PD leads to altera- early stages are important. Medicinal plants with antioxidant ac- tions in basal glutamatergic synaptic transmission of striatum and tivities, which are effective on PD have been recently reviewed plasticity in the medium spiny neurons [1]. PD affects 2% of the [12]. However, this review article only covers the Indian plants. population older than 65 years, with 7-10 million individuals af- In this paper, we reviewed the recently published papers on the fected worldwide [2]. Its symptoms include resting tremor, rigidity effects of herbal medicines on PD alongside the pathogenesis of PD of muscles, bradykinesia, and postural and gait impairments [3]. with regard to oxidative stress. The most cases of Parkinson’s disease are sporadic, with unde- PATHOGENESIS OF PD termined etiology. However, exposure to environmental toxins, About 50 years ago the dopaminergic defect was suggested as head trauma, inflammation, and free radicals are potential reasons the main neurochemical cause of PD; however, the exact causes of [4, 5]. Remarkable neuroinammation which is exacerbated by free this disease are not clear. About 10% of the patients with PD are radicals has been reported in the substantia nigra in the patients estimated to have mutations in selected genes. However, it has fur- with PD [6]. The neurotoxins and cytokines released from the reac- ther complicated the general picture about the underlying factors of tive inammatory cells cause distraction of the projecting dopa- PD [13]. minergic neurons in striatum and substantia nigra [6]. Neu- roinammation inhibition in the striatum and substantia nigra has In PD, there is a loss of dopaminergic neurons in substantia been shown to signicantly ameliorate the behavioral deciency in nigra with projecting nerve fibers residing in the striatum. These PD [7]. neurons play a crucial role in control of voluntary movements, and their degeneration usually leads to debilitating symptoms including Recently, special attention has been paid to the role of oxidative resting tremor, muscular rigidity, postural imbalance, and bradyki- stress in neurological abnormalities, including PD. In fact, exces- nesia. Aging is an important variable associated with the onset of sive production of reactive oxidative species (ROS) has been con- PD. So that, deficits in the normal cellular function that usually sidered as the cause of neuronal death [8, 9]. occur with aging increase the vulnerability of dopaminergic neu- There is no cure for PD yet, and treatment is mainly sympto- rons [14]. matic. The therapies based on a dopamine replacement consist of There is no single causative factor to identify sporadic PD. In the use of dopamine precursors; however, substantial adverse fact, a multi-factorial nature contributes to the process of nigral cell eects may appear in long-term usage. Novel pharmacotherapy and death, of which mitochondrial dysfunction and elevated levels in cell replacement, before being routinely used in humans, need ex- formation of ROS are the most important mechanisms [15]. An- tensive evaluation [10]. other factor which may contribute to the neuronal loss underlying The evidence that mitochondria and ROS as the main neurode- PD is neuro-inflammation which in turn increases the ROS and generation players have caused antioxidant remedies opens new exacerbates PD. The inflammatory response associated with the cell perspectives of research and therapy as possible preventive and loss in the dopaminergic nigrostriatal tract and the role of immune therapeutic approaches for PD [11]. mechanisms, which are associated with oxidative stress, are being increasingly addressed as important factors in the pathogenesis of PD [13]. *Address correspondence to this author at the Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran; Tel/Fax: +98 383 3330709; E-mail: [email protected] 1381-6128/16 $58.00+.00 © 2016 Bentham Science Publishers 2 Current Pharmaceutical Design, 2016, Vol. 22, No. 00 Sarrafchi et al. The Role of Free Radicals in PD DJ-1 and UCH-L1 have a cysteine residue which is crucial for Although familial forms of PD have been described, ROS is their activities. The oxidative modification of their cysteine has likely the main underlying mechanism in both genetic and idio- been reported in PD patients [24]. Dopamine quinone also can lead pathic cases of PD, leading to cellular dysfunction of dopaminergic to dysfunction of mitochondria and inactivation of tyrosine neurons. In this regard, the substantia nigra of PD patients contains hydroxyalase and dopamine transporter [16]. Furthermore, the higher levels of oxidized lipids, DNA and proteins as well as lower proteins that assist in protein folding in endoplasmic reticulum, levels of glutathione (GSH) [16]. including protein disulfide isomerase-5 and ER-60/GRP58/ERp57, are also modified by dopamine quinine [22]. Dopamine quinone Oxidative stress is potential when there is an imbalance be- also induces proteasomal inhibition leading to apoptosis of the cells tween ROS production and cellular antioxidant activity [17, 18]. [25]. Moreover, dopamine quinone is able to cyclize and become The major sources of ROS which cause oxidative stress and deficit the highly reactive aminochrome. In this form the redox-cycling in nigral dopaminergic neurons seem to be mitochondrial dysfunc- can lead to depletion of cellular nicotinamide adenine dinucleotide tion, neuroinflammation and dopamine metabolism [8]. phosphate (NADPH) and generation of superoxide, and ultimately Mitochondria are the main cellular source of free radicals and it may polymerize to form neuromelanin which exacerbates the have a crucial role in oxidative phosphorylation and electron trans- neurodegenerative process by triggering neuro-inflammation [26]. port [19]. Mitochondria are also involved in calcium homeostasis Neuromelanin is one of the final products of dopamine oxidation and regulation and instigation of cell-death pathways. Hence, there and is accumulated in the nigral region. Furthermore, during is a complex interaction between mitochondria function and other dopamine metabolism by monoamine oxidase, hydrogen peroxide parts of cellular machinery which affects cell survival. Notably, is also generated which is converted to the highly reactive hydroxyl mitochondrial dysfunction is not detected in all patients with PD. radical in the presence of transition metal ions, inducing oxidative However, this factor may have a critical contribution in the future stress [16]. treatment