Neuroprotection of Rotenone-Induced Parkinsonism by Ursolic Acid in PD Mouse Model

Abstract

Background: Parkinson’s disease (PD) is characterized by both motor and non-motor symptoms. The presynaptic neuronal protein, α-Synuclein, plays a pivotal role in PD pathogenesis and is associated with both genetic and sporadic origin of the disease. Ursolic Acid (UA) is a well-known bioactive compound found in various medicinal plants, widely studied for its anti-inflammatory and antioxidant activities. Objective: In this research article, the neuroprotective potential of UA has been further explored in Rotenone-induced mouse model of PD. Methods: To investigate our hypothesis, we have divided mice into 4 different groups, control, drug only control, Rotenoneintoxicated group, and Rotenone-intoxicated mice treated with UA. After the completion of dosing, behavioral parameters were estimated. Then mice from each group were sacrificed and the brains were isolated. Further, the biochemical tests were assayed to check the balance between the oxidative stress and endogenous anti-oxidants; and TH (Tyrosine Hydroxylase), αSynuclein, Akt (Serine-threonine protein kinase), ERK (Extracellular signal-regulated kinase) and inflammatory parameters like Nuclear factor-κB (NF-κB) and Tumor Necrosis Factor- α (TNF-α) were assessed using Immunohistochemistry (IHC).Western blotting was also done to check the expressions of TH and α-Synuclein. Moreover, the expression level of PD related genes like α-Synuclein, β-Synuclein, Interleukin-1β (IL-1β), and Interleukin- 10 (IL-10) were assessed by using Real-time PCR. Results: The results obtained in our study have suggested that UA significantly reduced the overexpression of α-Synuclein and regulated the phosphorylation of survival-related kinases (Akt and ERK) apart from alleviating the behavioral abnormalities and protecting the dopaminergic neurons from oxidative stress and neuroinflammation. Conclusion: Thus, our study puts forward the neuroprotective potential of UA which can be further explored for possible clinical intervention.

Unraveling the neuroprotective effect of Tinospora cordifolia in Parkinsonian mouse model through proteomics Approach.

“…Various studies reported that non motor symptoms generally develop at the initial stage of PD progression so that it is not able to differentiate PD patients from others. Zahra et al (2020) reported the characteristic motor impairment in ROT-intoxicated Parkinsonian mice [31]. To check the behavioral de cit in mice, we performed various behavioral tests such as catalepsy, rotarod, pole, and footprint, which highlighted severe motor abnormalities in ROT-intoxicated PD mouse model [42][43][44][45] (Figure 1).…”

“…per day) orallyadministered for 7 days, then concurrent administration of Tc (21 days) and ROT-intoxication (35 days) were done similar to that Rotenone group (n = 8/group). In accordance with our previous study, dosing was administered with minor changes [19,31]. Upon completion of the dosing, behavioral analysis was carried out, and the mice were sacri ced to isolate the brains for the proteome analysis.…”

Unraveling the Neuroprotective Effect of Tinospora Cordifolia in Parkinsonian Mouse Model Through Proteomics Approach.

“…Various studies reported that non motor symptoms generally develop at the initial stage of PD progression so that it is not able to differentiate PD patients from others. Zahra et al (2020) reported the characteristic motor impairment in ROT-intoxicated Parkinsonian mice [31]. To check the behavioral de cit in mice, we performed various behavioral tests such as catalepsy, rotarod, pole, and footprint, which highlighted severe motor abnormalities in ROT-intoxicated PD mouse model [42][43][44][45] (Fig 1).…”

Ferritinophagy‐Mediated Ferroptosis Involved in Paraquat‐Induced Neurotoxicity of Dopaminergic Neurons: Implication for Neurotoxicity in PD

“…Parkinson's disease (PD) is the most frequent and debilitating group of motor disorders in the elderly population [1,2] and has affected millions around the world from 1990 to 2015 [3]. The neuropathological features of PD are the loss of dopaminergic neurons in vulnerable brain regions, especially in the substantia nigra (SN) [4,5].…”