Title:Neuroprotection of Rotenone-Induced Parkinsonism by Ursolic Acid in PD Mouse Model
Volume: 19
Issue: 7
Author(s): Walia Zahra, Sachchida Nand Rai, Hareram Birla, Saumitra Sen Singh, Aaina Singh Rathore, Hagera Dilnashin, Richa Singh, Chetan Keswani, Rakesh K. Singh and Surya Pratap Singh*
Affiliation:
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi-221005,India
Keywords:
Parkinson`s disease, rotenone, α-synuclein, neuroinflammation, oxidative stress, ursolic acid.
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 the
Rotenone-induced mouse model of PD.
Methods: To investigate our hypothesis, we have divided mice into 4 different groups, control, drug
only control, Rotenone-intoxicated 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),
α-Synuclein, 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 levels 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 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 shows the neuroprotective potential of UA, which can further be explored
for possible clinical intervention.
