Neuroprotective effect of 25-Methoxyhispidol A against CCl4-induced behavioral alterations by targeting VEGF/BDNF and caspase-3 in mice
- 주제(키워드) 25-MHA , Anxiety , Apoptosis , Depression , Neurotrophic factors , Oxido-nitrasative stress
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Inc.
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168885
- 본문언어 영어
- Published As https://dx.doi.org/10.1016/j.lfs.2020.117684
- PubMed https://pubmed.ncbi.nlm.nih.gov/32315728
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Brain oxidative stress and neuroinflammation have been implicated in various psychiatric disorders. The current study investigated the effect and mechanism of 25-Methoxyhispidol A (25-MHA) against CCl4-induced anxiety and depression. Mice were challenged with CCl4 (1 ml/kg; i.p.) after 30 min of 25-MHA (1, 5 and 10 mg/kg; i.p.) administration. Pretreatment with 25-MHA (10 mg/kg) significantly attenuated the anxiety and depression-like behavior in testing models. The oxidative stress induced by CCl4 was significantly attenuated by pretreatment with 25-MHA. The immunohistochemical (IHC) analysis showed a reduction in kelch-like ECH-associated protein 1 (Keap1) and improvement in expression of nuclear factor erythroid-2-related factor (Nrf-2) and heme oxygenase (HO)-1. In addition, 25-MHA significantly attenuated the CCl4-mediated depletion of antioxidant enzymes in hippocampus (HC) and prefrontal cortex (PFC) region and reduced the expression of toll-like receptor (TLR)-4 and nuclear factor kappa B (NF-κB), along with a decreased production of pro-inflammatory cytokines in HC and PFC region. Pretreatment with 25-MHA also showed an improved expression of neurotrophic factors i.e., brain derived growth factor (BDNF) and vascular endothelial growth factor (VEGF). Furthermore, 25-MHA inhibited malondialdehyde (MDA) and ammonia level in plasma, liver, HC and PFC regions of mice brain. 25-MHA also exhibited anti-apoptotic effect evident from the reduced expression of caspase-3 and decreased hippocampal DNA damage in comet assay. Furthermore, decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and corticosterone level, along with prevention of CCl4-induced alterations in thickness of dentate gyrus and intact hepatic cells morphology, represented by hippocampal and liver histopathology, indicated the neuroprotective effect of 25-MHA. © 2020 Elsevier Inc.
more