Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

Abstract

SUMMARY:Among the neurodegenerative disorders, Parkinson disease (PD) is ranked as second most common. The pathological hallmark is selective degeneration of the dopaminergic neurons in the nigro-striatal regions of brain with appearance of the Lewy bodies. Present study explores the neuro-protective potential of polydatin in terms of amelioration of degeneration of dopaminergic neurons in nigro-striatal regions of brain and distorted neuromotor behavior in the rotenone model of Parkinson's disease. Thirty-six male Sprague Dawley rats were divided into three groups. Group A (control), Group B (rotenone treated) and Group C (rotenone+polydatin treated). Rotenone was administrated intraperitoneally (i.p) at a dose of 3 mg/kg/body weight while polydatin was given i.p. at a dose of 50 mg/ kg/body weight for four weeks. Then, animals were sacrificed; substantia nigra (SN) & striatum isolated from brain and five micron thick sections were prepared. Cresyl violet (CV), H&E and Immuno-histochemical staining using anti-TH antibody was done. Motor behavior was assessed weekly throughout the experiment using five different methods. Rotenone treated parkinsonian animals showed deterioration of motor behavior, weight loss, loss of dopaminergic neurons and diminished immune-reactivity in the sections from the nigrostriatal regions of these animals Polydatin+rotenone treatment showed contradicting effects to parkinsonism, with amelioration in weight loss, neuro-motor behavior, dopaminergic loss and immune-reactivity against dopaminergic neurons. Present study revealed a neuro-protective potential of polydatin in animal model of PD by ameliorating the neuro-motor abnormalities and degeneration of dopaminergic neurons in nigrostriatal regions.

Polydatin as a therapeutic alternative for central nervous system disorders: A systematic review of animal studies

“…Currently, we have at our disposal a range of damage‐inducing agents capable of reproducing PD as reliably as possible (de Andrade Teles et al, 2018). The studies included in this review used only neurotoxin‐based models to induce PD, including 6‐hydroxydopamine (6‐OHDA) (Y. Chen et al, 2015), lipopolysaccharide (LPS) (Huang et al, 2018), 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) (Y. Chen et al, 2015; S. Zhang, Wang, Shi, & Feng, 2020), and rotenone (Ahmed et al, 2018; Y. Chen et al, 2015).…”

“…In general, all of the studies demonstrated the beneficial effects of polydatin at different dosages and administration protocols on the behavioral performance of animals chemically induced to PD. Polydatin prevented motor coordination, muscle performance, and balance dysfunctions, as detected by the rotarod test (Y. Chen et al, 2015), and the occurrence of tremors, bradykinesia, and rigidity, as evaluated by the catalepsy test (Ahmed et al, 2018; Y. Chen et al, 2015). Some studies used an apomorphine‐induced rotational test to detect damage to the dopaminergic system and behavioral dysfunction in PD animals and verified that polydatin was able to decrease rotational movement (Y. Chen et al, 2015; Huang et al, 2018).…”

“…Some studies used an apomorphine‐induced rotational test to detect damage to the dopaminergic system and behavioral dysfunction in PD animals and verified that polydatin was able to decrease rotational movement (Y. Chen et al, 2015; Huang et al, 2018). Better tactile perception and movement coordination in the patch removal test and manual gait analysis, respectively, were observed after cotreatment with polydatin (Ahmed et al, 2018). The general locomotor activity in the open field test was also improved by polydatin when compared to PD untreated animal groups (Huang et al, 2018; S. Zhang et al, 2020).…”

“…Studies have demonstrated that polydatin or its metabolites can cross the blood–brain barrier (BBB), making it plausible to explore the neuroprotective potential of this compound (Huang et al, 2018; C. Lv et al, 2006). Several works have supported this hypothesis and demonstrated that polydatin can exert prophylactic and/or therapeutic effects in CNS disorders, including Parkinson's disease (PD; Ahmed et al, 2018; Y. Chen et al, 2015), stroke (Gao et al, 2016), cerebral ischemia (Ji et al, 2012; R. P. Li et al, 2012), traumatic brain injuries (Y. Li et al, 2019), and aging impairments (Xu et al, 2016). In view of the increasing incidence of neuropathologies and the lack of effective preventive and/or therapeutic alternatives for these disorders, a systematic review and synthesis of the data available for this compound in the literature could provide scientific support for future preclinical and clinical studies.…”

The Neuroprotective Role of Polydatin: Neuropharmacological Mechanisms, Molecular Targets, Therapeutic Potentials, and Clinical Perspective

“…They also indicated that polydatin improved neuromotor behavior in a rat model of rotenone-induced PD. Thus, the protective effect of polydatin against striatal degeneration is presented in their report [ 68 ]. In a similar report, polydatin meaningfully prevented the rotenone-induced dysregulations of MDA, manganese SOD, glutathione, and thioredoxin in the striatum.…”