BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Xuejun Jiang,Pengcheng Wu,Hui Chen,Jialu Cui,Xiting Lv,Linna Ha,Mingyang Wu,Min Chen,Baojian Wu,Haiman Xu,Dong Dong
Intestinal bowel disease (IBD), prevalent among sleep-deprived populations, is closely associated with circadian rhythm disruptions. Evidence suggests that sleep deprivation (SD) exacerbates colitis; however, the mechanisms is remains poorly understood. We subjected mice with Dextran sulfate sodium (DSS) induced acute and chronic colitis to 6 h-SD per day. It was observed that mild SD significantly aggravated both acute and chronic colitis, involving progressive body weight loss, increased Disease Activity Index (DAI), shortened colon length, histopathological deterioration, and elevated levels of inflammatory cytokines. Circadian gene screening identified PER2 as a pivotal mediator in SD aggravating colitis. Both SD and colitis independently suppressed Per2 expression in mice colon. Notably, the inhibitory effect on PER2 was most pronounced in cases of colitis accompanied by SD. Consistent with this, Per2 deficiency heightened the susceptibility of mice to DSS-induced colitis. Furthermore, transcriptomic analysis revealed that the disordered arachidonic acid (AA) metabolism pathway was implicated in the exacerbation of colitis due to Per2 deficiency. Specifically, Ptgs2 , a gene coding AA metabolism enzyme COX-2, was significantly upregulated in both Per2 -/- colitis mice and SD colitis mice. The elevated PGE 2 levels in plasma and colon supported the involvement of COX-2 mediated proinflammatory conversion of AA during episodes of SD-related colitis aggravation. Mechanistically, in vitro experiments in CT-26 cells suggested Per2 suppressed COX-2 transcription via BMAL1. In summary, SD inhibited the expression of clock factor PER2 in colon, leading to disorder of COX-2-mediated AA metabolism; this process released more pro-inflammatory mediators thereby aggravating colitis
研究领域:
免疫学
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分子生物学
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胃肠病学
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时间生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2023
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IF 7.9
Sanli Zhang,Yan Yu,Mingyue Sheng,Xun Chen,Qi Wu,Junping Kou,Gangling Chen
Background Ruscogenin (Rus), a steroidal sapogenin extracted from Ophiopogon japonicus (L. f.) Ker-Gawl., has the effect of alleviating cerebral ischemia-reperfusion injury (IRI), acute lung injury . At present, the chronopharmacological effects of Rus are still unknown. Purpose This study explored the alleviating effect and mechanism of Rus timing administration on mice cerebral IRI. Methods The animals in different groups were administrated Rus (10 mg/kg) by gavage at four time points (23:00–01:00, 05:00–07:00, 11:00–13:00, 17:00–19:00) respectively for 3 days. On the 4th day, middle cerebral artery occlusion (MCAO) surgery was operated during 5:00–7:00. Behavioral tests were executed and the brain was collected for infarct volume , qPCR and immunoblot detection. The levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin-1beta (IL-1β) and inducible nitric oxide synthase (iNOS) were detected by qPCR. Glutathione (GSH), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in serum and cerebral cortex were detected. The clock genes were tested by western blot. Based on these results, 17:00–19:00 was selected to administrate Rus for further mechanism study and Nrf2 blocker group was administrated all-trans-retinoic acid (ATRA) at 14:00 for 3 days. Results Administration of Rus reduced cerebral infarcted volume, ameliorated the behavior score and upregulated the mRNA and protein expression of Per1, Bmal1, Clock, Rev-erbα, transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1). Administration of Rus during 17:00–19:00 had better preventive effect than other three time points. Combined administration of ATRA blunted the preventive effect of Rus. Conclusion The preventive effect of Rus is affected by the time of administration, which was regulated by Nrf2 pathway. Taken together, we provide solid evidence to suggest that different administration time point affect the effectiveness of Rus in alleviating IRI.
研究领域:
药理学
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神经科学
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分子生物学
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生物钟学
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产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
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2021
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IF 4.418
Peng Wang,Xiaoxia Gao,Fang Zhao,Yao Gao,Kexin Wang,Jun-Sheng Tian,Zhenyu Li,Xue-Mei Qin
Depression has drawn increasing attention from the public around the world in recent years. Studies have shown that liver injury caused by chronic stress is relevant to depression and neurotransmitter changes. It is essential to clarify the relationship between neurotransmitter changes and hepatic gene expression in depression. In this study, we used the chronic unpredictable mild stress (CUMS) model combined with UHPLC–MS to explore the changes of neurotransmitters in serum and hippocampus and to decipher the differential gene expression in the liver by using the RNA-Seq combined with multivariate statistical analysis. Compared with the control group, the levels of neurotransmitters including 5-hydroxytryptamine (5-HT), acetylcholine, glutamate (Glu), and dopamine (DA) in the hippocampus and 5-HT, norepinephrine, γ-aminobutyric acid (GABA), and 5-hydroxyindoleacetic acid in serum were significantly changed in the CUMS rats. The results of liver transcriptomic analysis and correlation analysis showed that the Glu, DA, 5-HT, and GABA were impacted by 68 liver genes which were mainly enriched in three pathways including circadian rhythm, serotonergic synapse, and p53 signaling pathway. The expressive levels of clock genes and serotonergic synapse genes were validated by using q-PCR, and the diurnal rhythms of neurotransmitters were validated by in vivo hippocampus microdialysis. The CUMS stressors might cause phase advance of Glu and GABA by adjusting clock genes. The transcriptomic technique combined with correlation analysis and in vivo microdialysis could be used to discover comprehensive pathways of depression. It provides a new strategy for the rational assessment of the mechanism of disease.
研究领域:
神经科学
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药理学
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分子生物学
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转录组学
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行为科学
✓ 已验证
DOI
PubMed
高影响因子
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