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Neuroprotective effect of 25-Methoxyhispidol A against CCl4-induced behavioral alterations by targeting VEGF/BDNF and caspase-3 in mice

Title
Neuroprotective effect of 25-Methoxyhispidol A against CCl4-induced behavioral alterations by targeting VEGF/BDNF and caspase-3 in mice
Authors
Shal, BushraKhan, AdnanNaveed, MuhammadAli, HussainSeo, Eun KyoungChoi, HyukjaeKhan, Salman
Ewha Authors
서은경
SCOPUS Author ID
서은경scopus
Issue Date
2020
Journal Title
LIFE SCIENCES
ISSN
0024-3205JCR Link

1879-0631JCR Link
Citation
LIFE SCIENCES vol. 253
Keywords
AnxietyDepression25-MHAOxido-nitrasative stressApoptosisNeurotrophic factors
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
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-kappa B), 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.
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DOI
10.1016/j.lfs.2020.117684
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약학대학 > 약학과 > Journal papers
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