☆ 4.7 Article

The potential neuroprotective effect of diosmin in rotenone-induced model of Parkinson's disease in rats

EUROPEAN JOURNAL OF PHARMACOLOGY (2022)

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EUROPEAN JOURNAL OF PHARMACOLOGY

Volume 914, Issue -, Pages -

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ELSEVIER

DOI: 10.1016/j.ejphar.2021.174573

Keywords

Parkinson's disease; Rotenone; Diosmin; Neuroinflammation; Apoptosis; Oxidative stress

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Abstract

The study found that diosmin (DM) has neuroprotective effects in Parkinson's disease (PD) and can act through various mechanisms such as anti-inflammatory and antioxidative properties. These findings suggest that DM may be a promising candidate for managing the neuropathological course of PD.

Most treatments for Parkinson's disease (PD) focus on improving the symptoms and the dopaminergic effects; nevertheless, they cannot delay the disease progression. Diosmin (DM), a naturally occurring flavone that is obtained from citrus fruits, has demonstrated anti-apoptotic, anti-inflammatory and antioxidative properties in many diseases. This study aimed to assess the neuroprotective effects of diosmin in rotenone-induced rat model of PD and investigate its potential underlying mechanisms. A preliminary dose-response study was conducted where rats were treated with DM (50,100 and 200 mg/kg, p.o.) concomitantly with rotenone (2 mg/kg, s.c.) for 4 weeks. Catalepsy, motor impairment, spontaneous locomotion, body weight, histological examination and tyrosine hydroxylase (TH) immunoreactivity were evaluated in both the midbrains and striata of rats. Treatment with DM (200 mg/kg) showed the most promising outcome therefore, it was selected for further evaluation of alpha-synuclein, Bax, Bcl2, nuclear factor kappa B (NF-KB), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1), in addition to biochemical analysis of tumor necrosis factor-alpha (TNF-alpha). Results showed that DM (200 mg/kg, p.o.) prevented rotenone-induced motor impairment, weight reduction and histological damage. Furthermore, it significantly inhibited rotenone-induced decrease in TH expression. These results were correlated with reduction in alpha-synuclein immunoreactivity, together with improvement of Bax/Bcl2 ratio compared to rotenone group. DM also attenuated rotenone-induced increase in NF-KB expression as well as TNF-alpha levels. Moreover, DM inhibited rotenone-induced upregulation of Nrf2/HO-1 pathway. Thus, the current study suggests that DM might be a promising candidate for managing the neuropathological course of PD.

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Synergistic effects of lipopolysaccharide and rotenone on dopamine neuronal damage in rats

Jing-Yi He, Dai-Di Li, Qian Wen, Ting-Yang Qin, Hong Long, Shi-Bin Zhang, Feng Zhang

Summary: The etiology of Parkinson's disease (PD) is still unknown, but oxidative stress and neuroinflammation play a crucial role in its pathogenesis. This study found that lipopolysaccharide (LPS)-induced neuroinflammation and rotenone (ROT)-induced oxidative stress synergistically aggravated motor dysfunction, dopamine neuron damage, glial cell activation, release of related mediators, activation of Nrf2 signaling, and disruption of oxidative balance in the rat brain. Furthermore, oxidative stress followed by neuroinflammation caused more dopamine neuronal loss than neuroinflammation followed by oxidative stress.

CNS NEUROSCIENCE & THERAPEUTICS (2023)