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

• Published in: European journal of pharmacology 2022-01, Vol.914, p.174573-174573, Article 174573
• Main Authors: Habib, Christine N., Mohamed, Mohamed R., Tadros, Mariane G., Tolba, Mai F., Menze, Esther T., Masoud, Somia I.
• Format: Article
• Language: English
• Subjects: alpha-Synuclein - metabolism; Animals; Apoptosis; bcl-2-Associated X Protein - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Diosmin; Diosmin - pharmacology; Disease Progression; Dose-Response Relationship, Drug; Flavones - pharmacology; Mesencephalon; Neuroinflammation; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - metabolism; Neuroprotective Agents - pharmacology; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Oxidative stress; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rotenone; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation - drug effects
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2021.174573

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. •Diosmin significantly improved rotenone-induced motor impairment.•It prohibited rotenone-induced α-synuclein accumulation in rats' midbrains and striata.•It decreased rotenone-induced increase in Bax/Bcl-2 ratio.•It inhibited rotenone-induced increase in NF-кB expression as well as TNF- α levels.•It suppressed rotenone-induced upregulation of Nrf2 and HO-1 expression.