The potential neuroprotective effect of diosmin in rotenone-induced model of Parkinson's disease in rats
Habib, Christine N; Tadros, Mariane G; Tolba, Mai; Menze, Esther; Masoud, Somia I; Mohamed, Mohamed R;
Abstract
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 α-synuclein, Bax, Bcl2, nuclear factor kappa B (NF-кB), nuclear factor erythroid 2- related factor 2 (Nrf2), and heme oxygenase-1 (HO-1), in addition to biochemical analysis of tumor necrosis factor-α (TNF-α). 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 α-synuclein immunoreactivity, together with improvement of Bax/Bcl2 ratio compared to rotenone group. DM also attenuated rotenone-induced increase in NF-кB expression as well as TNF- α 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.
Other data
Title | The potential neuroprotective effect of diosmin in rotenone-induced model of Parkinson's disease in rats | Authors | Habib, Christine N; Tadros, Mariane G; Tolba, Mai ; Menze, Esther ; Masoud, Somia I; Mohamed, Mohamed R | Keywords | Apoptosis; Diosmin; Neuroinflammation; Oxidative stress; Parkinson's disease; Rotenone | Issue Date | 5-Jan-2022 | Publisher | ELSEVIER | Journal | European journal of pharmacology | Volume | 914 | ISSN | 0014-2999 | DOI | 10.1016/j.ejphar.2021.174573 | PubMed ID | 34656609 | Scopus ID | 2-s2.0-85121211205 | Web of science ID | WOS:000754694600003 |
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