JOURNAL OF ANIMAL SCIENCE
·
2024
·
IF 2.7
Liu Jie,Zhang Ke,Zhao Mindie,Chen Liang,Chen Huimin,Zhao Yulan,Zhao Ruqian
The aim of this study was to investigate the alleviating effects and mechanisms of bile acids (BA) on corticosterone-induced fatty liver in broiler chickens. Male Arbor Acres chickens were randomly divided into three groups: control group (CON), stress model group (CORT), and BA-treated group (CORT-BA). The CORT-BA group received a diet with 250 mg/kg BA from 21 days of age. From day 36 to 43, both the CORT and CORT-BA groups received subcutaneous injections of corticosterone to simulate chronic stress. The results indicated that BA significantly mitigated the body weight loss, liver enlargement, and hepatic lipid deposition caused by corticosterone (P < 0.05). Liver RNA-seq analysis showed that BA alleviated corticosterone-induced fatty liver by inhibiting lipid metabolism pathways, including fatty acid biosynthesis, triglyceride biosynthesis, and fatty acid transport. Additionally, BA improved corticosterone-induced downregulation of glucocorticoid receptor (GR) expression (P < 0.05). Molecular docking and cellular thermal shift assays revealed that hyodeoxycholic acid (HDCA), a major component of compound bile acids, could bind to GR and enhance its stability. In conclusion, BA alleviated corticosterone-induced fatty liver in broilers by inhibiting lipid synthesis pathways and mitigating the suppression of hepatic GR expression.
研究领域:
动物科学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Mengru Chen,Yifei He,Yimin Jia,Lei Wu,Ruqian Zhao
Avian pathogenic Escherichia coli ( APEC ) infection has high morbidity and mortality, and multiple stressors encountered during rearing place poultry in a state of stress. However, research on how poultry cope with APEC infection under stress situation is still limited. In this study, we established a broiler stress model by corticosterone ( CORT ) administration subcutaneously for 7 consecutive days, followed by APEC challenge intramuscularly. CORT treatment significantly reduced body weight ( BW ) and average daily gain ( ADG ) while increasing feed conversion ratio ( FCR ) ( P < 0.01). APEC infection significantly decreased ADG ( P < 0.01). CORT treatment and APEC infection elevated plasma corticosterone and heterophil to lymphocyte ( H/L ) ratio ( P < 0.05). Additionally, plasma aspartate aminotransferase ( AST ), AST to alanine aminotransferase ( AST/ALT ) ratio, and lactate dehydrogenase ( LDH ) levels increased significantly ( P < 0.01). Histopathological analysis revealed structural damage of liver, indicating that CORT treatment and APEC infection induced liver injury. However, CORT pretreatment broilers exhibited a milder histopathological lesions and significantly lower AST, ALT, and LDH levels ( P < 0.05) compared to APEC infection alone. CORT treatment and APEC infection increased plasma levels of lysozyme ( LZM ), total protein ( TP ), and globulin ( GLOB ) ( P < 0.05), while CORT pretreatment further elevating their concentrations compared to APEC infection alone, suggesting an enhanced innate immune response. Liver transcriptomic analysis identified 768, 335, and 567 differentially expressed genes ( DEGs ) following CORT, APEC, or both treatments, respectively, enriched in cytokine-cytokine receptor interaction, PPAR signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, steroid hormone biosynthesis pathway, arachidonic acid metabolism, and phagosome pathway, etc., indicating that CORT treatment regulates lipid metabolism and immunity, while APEC infection induces inflammation and disrupts lipid metabolism. Notably, CORT pretreatment may mitigate APEC induced liver injury by enhancing phagosome function. Moreover, glucocorticoid receptor ( GR ) may regulate DEGs expressions, thus affected broilers response to CORT, APEC, or both treatments. These results suggest that CORT treatment, APEC infection, or both significantly affect the growth performance, immune response and liver function of broilers, while lipid metabolism may play a crucial role.
研究领域:
动物科学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
·
2025
·
IF 2.3
Huimin Chen,Ke Zhang,Hui Yu,Ziting Guan,Ruqian Zhao,Lei Wu
Stress is a primary contributor to fatty liver syndrome (FLS) in chickens. Mitochondrial functionality is pivotal in FLS progression, with diminished supercomplex (SC) formation disrupting electron transport and escalating reactive oxygen species (ROS) production. However, the impact of stress on mitochondrial SC in chicken FLS remains elusive. This study employed corticosterone (CORT) to model chronic stress and examined its consequences on mitochondrial performance and SC configuration in both vivo and vitro FLS models. Notably, the CORT-treated hepatocytes exhibited elevated triglyceride content (P < 0.05), accompanied by increased mitochondrial ROS (P < 0.01). Moreover, CORT-exposed broilers displayed reduced body weight (P < 0.05) alongside heightened liver-to-body weight ratio (P < 0.01), indicative of liver steatosis with increased triglyceride levels in both liver and plasma (P < 0.01). Mitochondrial alterations in reduced ATP content (P < 0.05). Gene expression analysis revealed enrichment in the mitochondrial respiratory chain pathway, with down-regulated mRNA expression of Complex I-associated SC assembly factors NDUFAF5, NDUFAF7, and TIMMDC1 (P < 0.05). Meanwhile, the glucocorticoid receptor (GR) protein level and its specific binding to the NDUFAF5 gene promoter were reduced in the CORT group (P < 0.01 and P < 0.05, respectively), accompanied by a decrease in NDUFAF5 protein expression in liver, primary hepatocytes, and AML12 cells (P < 0.05). GR knockdown in AML12 cells reduced NDUFAF5 protein expression (P < 0.05). Thus, these findings imply that GR-mediated transcriptional regulation of Complex I assembly factor NDUFAF5 may influence SC assembly, shedding light on stress-induced FLS mechanisms in broilers.
研究领域:
动物科学
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分子生物学
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兽医学
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DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2022
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IF 4.014
Mingfa Sun,Hongchao Jiao,Jingpeng Zhao,Xiaojuan Wang,Haifang Li,Yunlei Zhou,Hai Lin
Stress is a common problem diminishing the muscle development of broilers. Creatine ( Cr ), an energy buffer in skeletal muscle, plays a fundamental role in muscle physiology. This study aimed to evaluate the effect of Cr monohydrate (CMH) on protein breakdown in chicken myotubes challenged by corticosterone (CORT) in vitro. The morphology of myotube was measured and the activation of ubiquitin proteasome ( UP ) pathway was determined. The result showed that CORT treatment decreased myotube diameter ( P < 0.05), increased 3-methyl-histidine (3M-His) content in medium, enhanced the mRNA expression levels of muscle ring finger1 ( MuRF1 ) and Atrogin1 ( P < 0.001), and Atrogin1 protein level ( P < 0.05) compared with control. By contrast, CMH increased myotube diameter ( P < 0.05) and myosin heavy chain ( MHC ) expression ( P < 0.001), whereas decreased 3M-His and the mRNA and protein levels of Atrogin1 ( P < 0.05), compared to control. In the present of CMH, the decreased myotube diameter and increased 3M-His, mRNA levels of MuRF1 and Atrogin1 , and Atrogin1 protein level by CORT were partially relieved ( P < 0.05). Hence, the result suggests that CMH alleviates CORT-induced protein breakdown by suppressing Atrogin1 expression in chicken myotubes. The result highlights the potential application of CMH in regulating muscle protein catabolism in chickens under stress.
研究领域:
动物生理学
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肌肉生物学
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应激生理学
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产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
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2025
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IF 2.5
Ma Qi,Ma Yu,Sun Shizhuo,Yang Lei,Shi Tian,Zhang Boxi,Shang Bo,Zhou Ruiyuan,Liu Jingyuan,He Jiao,Hu Jing,Cao Yanjun
Geniposide (GE), an iridoid glycoside from Gardenia jasminoides J.Ellis , exhibits anti-inflammatory, antioxidant, antidepressant, and neuroprotective properties. The excessive presence of corticosterone (CORT) can lead to neurotoxicity and inflict harm upon nerve cells. This study aimed to examine GE’s neuroprotective effects on CORT-induced damage in PC12 cells. Cells were pre-treated with GE for 3 h, then exposed to CORT for 24 h. Cell viability and lactate dehydrogenase (LDH) leakage were measured, apoptosis was assessed via flow cytometry, and immunofluorescence was used to detect MAP2 and PSD95 expression. The detection of glutamate (Glu) receptor, BDNF pathway, synaptic plasticity-related protein, and apoptosis pathway were performed using Western blot. The findings indicated that GE effectively prevented the reduction in cell viability, apoptosis, and LDH release caused by CORT. In PC12 cells, the expression of MAP2 and PSD95 were significantly enhanced by GE. Furthermore, GE reduced NR1, NR2A, NR2B, and Bax levels, increased EAAT2/3, Bcl-2, and proteins linked to BDNF and synaptic plasticity, and inhibited Caspase-3 and Caspase-9. GE shows neuroprotective and anti-apoptotic properties against CORT-induced cellular damage through BDNF pathway activation and Bax/Bcl-2 pathway suppression.
研究领域:
神经药理学
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细胞生物学
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植物化学
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分子生物学
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神经科学
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2018
·Vol. 15
·期 5
·4284-4290
·
IF 1.41
Sha Feng,Jue Liu,Biao Cheng,Aiping Deng,Hong Zhang
It has been acknowledged that environmental stress is a risk factor for developing mental disorders. Chronic stress may contribute to the hyperactivation of the hypothalamic‑pituitary‑adrenal (HPA) axis and a sustained rise in the levels of glucocorticoids (GCs). A high concentration of corticosterone (CORT) damages neuronal PC12 cells. It has been reported that (‑)‑Epigallocatechin‑3‑gallate (EGCG), a major component of green tea, exhibits neuroprotective activity. However, the protective effect of EGCG on neuronal cells injured by CORT remains to be elucidated. The present study aimed to identify the effects of EGCG on CORT‑injured neuronal PC12 cells and its associated mechanisms of action. CORT‑injured PC12 cells were pretreated with EGCG with or without cyclopamine. Cell viability was assessed using an MTT assay, changes in cell morphology were observed using phase‑contrast microscopy, cellular apoptosis was assessed by Hoechst 33342 staining, cell proliferation was measured using a cell counting kit‑8 assay, mRNA levels were measured by reverse transcription‑quantitative polymerase chain reaction and protein expression was assessed using western blot analysis. The current study demonstrated that exposure to high concentrations of CORT induced cytotoxicity and downregulated the Sonic hedgehog pathway (Shh) in PC12 cells. These effects were attenuated by EGCG. However, the EGCG‑mediated neuroprotective effects, as well as upregulation of the Shh pathway were all attenuated by the Shh signaling inhibitor cyclopamine. These results indicate that EGCG protects PC12 cells from CORT‑induced neurotoxicity via activation of the Shh signaling pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Sun Jia-Yi,Liu Yi-Tong,Jiang Sheng-Nan,Guo Peng-Mei,Wu Xin-Yu,Yu Jia
For thousands of years, the roots of Paeonia lactiflora Pall (PLP) has been considered by traditional Chinese medicine as a drug that can improve mental or emotional disorders, including depression, anxiety and affective disorders. Unfortunately, the research on the mechanism of action and active ingredients of this beneficial drug is not comprehensive. This study focused on the activity of essential oil from PLP (EOP), systematically studied the antidepressant effect of EOP for the first time, and discussed the potential mechanism of its antidepressant effect. In this study, we used a mouse model of corticosterone (CORT)-induced depression, and found that EOP had a significant antidepressant effect on the symptoms of CORT-induced depression in mice, and significantly down-regulated the levels of CRH, ACTH and cortisol in the brain tissues of mice. In addition, we found that EOP treatment alleviated CORT-induced hippocampal neuron injury in mice In vitro experiments. It was also found that EOP could inhibit CORT-induced apoptosis and improve the proliferation ability and cell viability of PC12 cells. Further, with the help of network analysis, it was revealed that PI3K-Akt might be one of the main signaling pathways of EOP against CORT-induced hippocampal neuron apoptosis. In this study, we also found that EOP up-regulated the phosphorylation of PI3K and Akt in CORT-induced mouse hippocampal neurons and PC12 cells, and promoted the nuclear transcription of Nrf2 in CORT-induced PC12 cells. In conclusion, with the integrated approach, we demonstrated that EOP exerted anti-apoptotic effects on hippocampal neurons through PI3K/Akt/Nrf2 signaling pathway.
研究领域:
药理学
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神经科学
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传统中药
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2022
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IF 3.571
Zhenyao Lu,Sijia Li,Nan Aa,Yuanmao Zhang,Ran Zhang,Chen Xu,Shize Zhang,Xiangqing Kong,Guangji Wang,Jiye Aa,Yue Zhang
Purine and pyrimidine metabolism are vital metabolic pathways in the development, proliferation or repairment of cells or tissues associated with various diseases. Here, a simple, all-in-one injection hydrophilic interaction liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of 20 metabolites: adenine , adenosine, deoxyadenosine , adenosine 5′-monophosphate, cyclic adenosine monophosphate, hypoxanthine , xanthine , inosine , deoxyinosine , xanthosine , xanthosine 5′-monophosphate and uric acid , which are products of purine metabolism; uridine , deoxyuridine , uridine 5′-monophosphate and uracil , are products of pyrimidine metabolism; and corticosterone , methionine , acetylcholine and serotonin. To minimize interference of endogenous molecules in sample matrixes, a combination of activated carbon adsorption and a serum substitute matrix (5% bovine serum albumin in phosphate buffered saline) was utilized and jointly applied. The sensitivity, linearity, stability, precision, accuracy and extraction recovery were evaluated, and the method was demonstrated to be accurate, sensitive and reliable. An analytical strategy was successfully applied to quantitatively determine 20 metabolite levels in the serum and hippocampus of mice with chronic social defeat stress-induced depression. The results showed greatly perturbed purine metabolism in the depressed mice, which was primarily characterized by dramatic increases in hypoxanthine, xanthine and inosine in serum and reduced levels of adenine, adenosine and adenosine 5′-monophosphate in the hippocampus. These findings suggest that this novel strategy can facilitate the quantitative analysis of adenine and other purine and pyrimidine metabolites in tissue and serum and exhibits great potential in the exploration of metabolism-related mechanisms of relevant diseases.
研究领域:
生物化学
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医学
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神经科学
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DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2022
·Vol. 179
·期 17
·4440-4456
·
IF 9.473
Mengru Bai,Mingyang Chen,Qingquan Zeng,Shuanghui Lu,Ping Li,Zhiyuan Ma,Nengming Lin,Caihong Zheng,Hui Zhou,Su Zeng,Dongli Sun,Huidi Jiang
Background and Purpose Plasma triglyceride (TG) levels increase as gestation proceeds, and abnormal elevation of TG increases the risk of pregnancy complications. The current study explored the mechanisms involved in hypertriglyceridaemia during pregnancy. Experimental Approach Lipid profile and expression levels of key genes involved in liver TG metabolism in non-pregnant and pregnant mice were studied. The effects of pregnancy-related hormones on key genes and the underlying mechanisms were uncovered in vitro and in vivo. Key Results Plasma and hepatic TG levels were elevated, while hepatic fatty acid translocase (FAT/CD36) was up-regulated in pregnant mice. Corticosterone and cortisol (endogenous glucocorticoids that are elevated during pregnancy), but not oestradiol or progesterone, significantly up-regulated CD36 in hepatocytes, and this was abolished after knockdown of the glucocorticoid receptor (GR) using a siRNA or in the presence of GR antagonists, RU486 and AL082D06. The luciferase reporter gene and chromatin immunoprecipitation assay further revealed that corticosterone/cortisol promoted the direct binding of GR to the CD36 promoter and up-regulated its transcription. Chronic corticosterone exposure induced liver lipid accumulation and increased plasma TG levels in mice, which were attenuated by RU486 via inhibition of the GR-CD36 pathway. Conclusions and Implications Increased corticosterone/cortisol induces liver lipid accumulation and hypertriglyceridaemia during pregnancy by accelerating fatty acid uptake into hepatocytes via activation of GR and its target gene, CD36. Our results may be useful for the prevention of severe hypertriglyceridaemia and associated pregnancy complications. Graphical
研究领域:
内分泌学
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肝病学
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药理学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Tian-tian Wang,Meng-yuan Zhou,Xue-na Gong,Yan Huang,Fei-long Li,Sheng-long Gu,Man-yu Zhang,Ling-ling Li,Ze-shan Xu,Rong Li,Li Cai
Eupalinolide B (EB), a primary bioactive compound isolated from Eupatorium lindleyanum DC ., has exhibited various pharmacological properties, such as antitumor, anti-inflammatory, and notably, neuroprotective effects in neurodegenerative diseases. However, the in-depth studies on the antidepressant potential of EB and its underlying mechanisms are still lacking. Herein, we investigated the therapeutic effects of EB on corticosterone (CORT)-induced neurotoxicity in PC12 cells and its antidepressant-like effects in rats subjected to chronic unpredictable mild stress (CUMS). In particular, we focused on the molecular mechanisms related to modulating the GSK-3β/β-catenin pathway. Our findings revealed that EB promoted cell proliferation while decreasing apoptosis and oxidative stress in CORT-induced PC12 cells. In vivo, EB alleviated the depressive-like behaviors in CUMS rats, as assayed by the sucrose preference test, open field test, and forced swim test. Additionally, EB attenuated the hippocampal pathological damage and increased Ki67- and doublecortin-positive cell numbers in hippocampal dentate gyrus, thus restoring hippocampal neurogenesis in CUMS rats. The binding of EB to GSK-3β was confirmed using molecular docking and cellular thermal shift assays. Overexpression of GSK-3β diminished the therapeutic effects of EB on CORT-induced PC12 cells, further indicating that GSK-3β is the target of EB. Mechanistically, EB hindered GSK-3β activity and thus activated β-catenin signaling in both CORT-induced PC12 cells and CUMS rat hippocampus, as demonstrated by increased p-GSK-3β (Ser9), reduced p-β-catenin, and elevated β-catenin expression. Collectively, this study offers new insights into the antidepressant mechanisms of EB, highlighting its potential as a candidate for depression treatment.
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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产品关联
DOI
PubMed
高影响因子
Comparative Biochemistry and Physiology D-Genomics & Proteomics
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2021
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IF 2.674
Liming Chang,Bin Wang,Meihua Zhang,Jiongyu Liu,Tian Zhao,Wei Zhu,Jianping Jiang
Corticosterone (CORT)-mediated adaptive plasticity improves animal fitness in stressful environments. Although it brings ecological benefits, the cost potentially constrains its expression and evolution. Revealing the factors affecting plasticity costs is of great ecological and evolutionary significance. Evidence indicates that both CORT and background colour can induce metabolic changes in animals, which in turn determine phenotypic plasticity . However, whether and/or how CORT and background colour jointly act on plastic responses has not been studied. Here, this question has been investigated in amphibian tadpoles ( Microhyla fissipes ) exposed to CORT at different background colours (white or black) using integrated morphological, histological, and transcriptomic analyses. The results showed that CORT exposure increased relative tail length, immune function, and metabolic maintenance (i.e., transcription of substrate catabolism and oxidative phosphorylation) at the expense of reduction in growth rate and skin melanin level. The black background also increased relative tail length and metabolic maintenance (i.e., transcription of oxidative phosphorylation) at the cost of reduction in growth rate, but increased skin melanin level. The expression of critical pigmentation genes indicated that black background activated a distinct and opposite pigmentation regulating route to CORT. Although there was no interactive effect of background colour and CORT on phenotypic and metabolic variations, their additive effects further impact the trade-off between somatic growth, metabolic maintenance, and pigmentation in terms of resource allocation. In conclusion, the individual and additive effects of background colour and CORT exposure on tadpole plasticity were revealed. These results likely provide new insights into the environmental adaptation of animals.
研究领域:
生态学
·
进化生物学
·
生理学
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DOI
PubMed
高影响因子
Journal of Neurogastroenterology and Motility
·
2017
·
IF 2.457
Meng Li,Lu Xue,Hong-Yan Zhu,Hongjun Wang,Xue Xu,Ping-An Zhang,Geping Wu,Guang-Yin Xu
Background/Aims Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. Methods DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension. Results Incubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials induced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltage-gated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89. Conclusions Our data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection.
研究领域:
神经科学
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药理学
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生理学
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产品关联
DOI
PubMed
高影响因子
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