PMID- 34656609 OWN - NLM STAT- MEDLINE DCOM- 20220310 LR - 20220310 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 914 DP - 2022 Jan 5 TI - The potential neuroprotective effect of diosmin in rotenone-induced model of Parkinson's disease in rats. PG - 174573 LID - S0014-2999(21)00729-9 [pii] LID - 10.1016/j.ejphar.2021.174573 [doi] AB - 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-small ka, CyrillicB), 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-small ka, CyrillicB 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. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Habib, Christine N AU - Habib CN AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt. Electronic address: christine-nathan@pharma.asu.edu.eg. FAU - Mohamed, Mohamed R AU - Mohamed MR AD - Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt. FAU - Tadros, Mariane G AU - Tadros MG AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt. FAU - Tolba, Mai F AU - Tolba MF AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt; School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Egypt. FAU - Menze, Esther T AU - Menze ET AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt. FAU - Masoud, Somia I AU - Masoud SI AD - Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. LA - eng PT - Journal Article DEP - 20211014 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Bax protein, rat) RN - 0 (Bcl2 protein, rat) RN - 0 (Flavones) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (Neuroprotective Agents) RN - 0 (Nfe2l2 protein, rat) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Snca protein, rat) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (alpha-Synuclein) RN - 0 (bcl-2-Associated X Protein) RN - 7QM776WJ5N (Diosmin) RN - S2V45N7G3B (flavone) SB - IM MH - Animals MH - Corpus Striatum/drug effects/metabolism MH - Diosmin/*pharmacology MH - Disease Progression MH - Dose-Response Relationship, Drug MH - Flavones/pharmacology MH - Mesencephalon MH - NF-E2-Related Factor 2/metabolism MH - NF-kappa B/metabolism MH - Neuroinflammatory Diseases/drug therapy/metabolism MH - Neuroprotective Agents/pharmacology MH - *Parkinson Disease/drug therapy/metabolism/pathology MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Rats MH - Tumor Necrosis Factor-alpha/metabolism MH - Up-Regulation/*drug effects MH - alpha-Synuclein/*metabolism MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Apoptosis OT - Diosmin OT - Neuroinflammation OT - Oxidative stress OT - Parkinson's disease OT - Rotenone EDAT- 2021/10/18 06:00 MHDA- 2022/03/11 06:00 CRDT- 2021/10/17 20:37 PHST- 2021/08/26 00:00 [received] PHST- 2021/10/11 00:00 [revised] PHST- 2021/10/12 00:00 [accepted] PHST- 2021/10/18 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2021/10/17 20:37 [entrez] AID - S0014-2999(21)00729-9 [pii] AID - 10.1016/j.ejphar.2021.174573 [doi] PST - ppublish SO - Eur J Pharmacol. 2022 Jan 5;914:174573. doi: 10.1016/j.ejphar.2021.174573. Epub 2021 Oct 14.