Abstract
Parkinson’s disease (PD), a multifactorial movement disorder that involves progressive degeneration of the nigrostriatal system affecting the movement ability of the patient. Oxidative stress and neuroinflammation both are shown to be involved in the etiopathogenesis of PD. The aim of this study was to evaluate the therapeutic potential of thymol, a dietary monoterpene phenol in rotenone (ROT)-induced neurodegeneration in rats that precisely mimics PD in humans. Male Wistar rats were injected ROT at a dose of 2.5 mg/kg body weight for 4 weeks, to induce PD. Thymol was co-administered for 4 weeks at a dose of 50 mg/kg body weight, 30 min prior to ROT injection. The markers of dopaminergic neurodegeneration, oxidative stress and inflammation were estimated using biochemical assays, enzyme-linked immunosorbent assay, western blotting and immunocytochemistry. ROT challenge increased the oxidative stress markers, inflammatory enzymes and cytokines as well as caused significant damage to nigrostriatal dopaminergic system of the brain. Thymol treatment in ROT challenged rats appears to significantly attenuate dopaminergic neuronal loss, oxidative stress and inflammation. The present study showed protective effects of thymol in ROT-induced neurotoxicity and neurodegeneration mediated by preservation of endogenous antioxidant defense networks and attenuation of inflammatory mediators including cytokines and enzymes.
Highlights
Parkinson’s disease (PD) is pathologically described by the continued loss of dopaminergic neuronal cells in the substantia nigra pars compacta (SNc), which results in motor impairments such as loss of motion, postural and gait instability, resting tremors, and muscle rigidity [1,2]
thymol group (Thymol) (Figure 1), a monoterpene phenol was used to protect the dopaminergic neuronal death caused by ROT administration
We performed the immunohistochemical analysis of Tyrosine Hydroxylase (TH)+ neurons in the SNc and TH-ir fibers in the striatum to observe the effects of thymol on nigrostriatal dopaminergic loss
Summary
Parkinson’s disease (PD) is pathologically described by the continued loss of dopaminergic neuronal cells in the substantia nigra pars compacta (SNc), which results in motor impairments such as loss of motion, postural and gait instability, resting tremors, and muscle rigidity [1,2]. Oxidative stress and inflammation are the two central pathways in microglial cells activation that lead to progressive neuronal degeneration and represent an important therapeutic target in PD [3,4,5,6,7]. The restoration of the cellular antioxidant system using antioxidants is one of the emerging therapeutic strategies to protect susceptible dopaminergic neurons from oxidative stress and subsequent inflammation. The adverse effects of anti-inflammatory agents and the pro-oxidant action of the synthetic antioxidants are of concern in therapeutics. This concern shifted the focus of drug discovery to explore plant extracts and plant-derived phytochemicals that possess antioxidant and anti-inflammatory activities for their therapeutic and preventive benefits in PD [8,9]. In recent years, the focus of pharmacological therapy has been on the development of novel nutraceutical-based plant-derived phytochemicals that possess high antioxidant and anti-inflammatory properties, with a lesser degree of cytotoxic effects [9]
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