BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Xu Yao,Jie Zhu,Lin Li,Bo Yang,Bixia Chen,Endong Bao,Xiaohui Zhang
Severe heat stress can cause human and animal heart failure and sudden death, which is an important issue of public health worldwide. Our previous studies in animals showed that myocardial cells injury was critical in the above process, and Hsp90 induction has a definite anti-myocardial injury effect, especially through aspirin (ASA). But the mechanism has not been fully clarified. In this study, an in vitro heat stress model of chicken primary myocardial cells (CPMCs) most sensitive to heat stress was used to explore the cell injuries and corresponding molecular resistance mechanism. We found that heat stress resulted in serious oxidation stress and calcium overload in mitochondria, which destroyed the mitochondrial structure and function and then triggered the cell death mechanism of CPMCs. Hsp90 was proven to be a central regulator for resisting heat-stress injury in CPMCs mitochondria using its inhibitor and inducer (geldanamycin and ASA), respectively. The mechanism involved that Hsp90 could activate Akt and PKM2 signals to promote Bcl-2 translocation into mitochondria and its phosphorylation, thereby preventing ROS production and subsequent cell apoptosis . In addition, Hsp90 inhibited mitochondrial calcium overload to overcome MPTP opening and MMP suppression through the inhibitory effect of Raf-1-ERK activation on the CREB-IP3R pathway. This study is the first to reveal a pivotal reason for heat-stressed damage in chicken myocardial cells at subcellular level and identify an effective regulator, Hsp90, and its protective mechanisms responsible for maintaining mitochondrial homeostasis.
研究领域:
细胞生物学
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分子生物学
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心脏病学
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应激生物学
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产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Shu-zhen Ran,Rui Peng,Qin-wan Guo,Li-juan Ma,Jian-bo Wan,Jun-qing Huang,Zi-ying Wang,Gang Chen
Panax notoginseng Leaf (PNL), an edible-medicinal botanical resource, shows potential as functional ingredients for alleviating depression, owing to their unique saponin composition. This study investigates the regulatory effects of PNL-derived saponins on pituitary adenylate cyclase-activating polypeptide (PACAP) and their related antidepressant mechanisms. Our findings demonstrate that PNL supplementation significantly alleviates depressive-like behaviors. Mechanistically, PNL upregulates PACAP expression in the hippocampus and activates the downstream CREB and mTOR signaling pathways, leading to increased expression of synaptic plasticity markers, including BDNF and PSD95, while concurrently inhibiting microglial activation and the production of pro-inflammatory cytokines. Among the major saponins in PNL, ginsenosides Rb3 and Rc were found to synergistically enhance PACAP expression in the cultured PC12 cells. These results underscore the potential of PNL for novel functional food ingredients, highlighting the antidepressant synergism of its naturally occurring ginsenosides (Rb3/Rc), and provide a natural antidepressant strategy.
研究领域:
药理学
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神经科学
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植物学
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生物化学
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精神病学
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产品关联
DOI
高影响因子
Food Bioscience
·
2022
·
IF 5.318
Jingru Zheng,Yuanhong Gao,Jie Ding,Na Sun,Songyi Lin
The study aims to investigate the repair effects of Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) and Ser-Asn-Val-Phe-Asp-Met-Phe (SNVFDMF) peptides on scopolamine-caused memory impairment in mice. Behavioral experiments have revealed that Antarctic krill peptides can ameliorate scopolamine caused memory impairment by changing the behavior of mice. In comparison with the scopolamine group, the two peptides at a dose of 40 mg/kg could improve memory impairment. The serum SOD activity (82.82 ± 0.19 vs 79.47 ± 2.42 U/mg prot) and hippocampal ACh level (101.46 ± 3.23 vs 99.85 ± 7.13 μg/mg prot) of SSDAFFPFR were higher than those of SNVFDMF. Hippocampal AChE activity (0.20 ± 0.03 vs 0.53 ± 0.02 U/mg prot), hippocampal MDA level (1.56 ± 0.01 vs 1.63 ± 0.05 nmol/mg prot) and the serum MDA level (3.38 ± 0.24 vs 3.88 ± 0.21 nmol/mg prot) was lower than that of SNVFDMF. The state of mouse hippocampal cells was further observed by a microscopic imaging system. In addition, western blot analysis showed that SSDAFFPFR could significantly inhibit the expression of Bax, caspase-3, and p53, and promote the expression of BCL-XL, CREB, and BDNF, thus protecting hippocampal neurons in mice. In conclusion, the Antarctic krill peptide can repair scopolamine-induced memory impairment in mice.
研究领域:
神经科学
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药理学
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生物化学
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产品关联
DOI
高影响因子
Frontiers in Neuroscience
·
2025
·
IF 3.2
Mengjie He,Mengying Hu,Tingqiao Wang,Zeping Zuo,Hongkai Li,Zhiwei Zhao,Yunwen Hao,Xueling Dai,Jianfang Wang,Yaxuan Sun
Background: In recent years, depression has become a global public health concern, and one of the common concomitant symptoms are diminished sexual motivation and impaired sexual performance. The aim of this study was to investigate the potential effects of Morinda officinalis oligosaccharides (MOO) on depression and its concomitant symptom, sexual dysfunction.Methods: Chronic unpredictable mild stress (CUMS)-induced depression model was constructed, and the effects of MOO on depression and sexual abilities were evaluated.Results: The results revealed that MOO was able to alleviate CUMS-induced depression-like behavior in mice, to inhibit hippocampal neuron apoptosis, to reverse monoamine neurotransmitter imbalance, increase Brain-derived neurotrophic factor (BDNF) expression levels in the hippocampus, to modulate the composition and distribution of gut microbiota, and to increase the abundance of probiotics after continuous gavage of MOO for 28 days. MOO further confirmed that sexual dysfunction is closely related to the development of depression by improving the lack of sexual motivation and low sexual performance in CUMS-induced depressed mice, modulating the disruption of sex hormone secretion in serum, and alleviating sperm morphology and functional defects in the epididymis.Conclusion: These findings on MOO provide a basis for exploring its antidepressant mechanism, its use to improve hypogonadotropic symptoms, and for future development of new antidepressant drug to improves hypogonadotropic symptoms.
研究领域:
神经科学
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药理学
·
心理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Fenyi Min,Jiaqing Wang,Liping Qin,Yuxin Wang,Yizhou Li,Xuebo Liu,Lijun Sun
Plant-derived bioactive peptides have been suggested as a class of compounds with neuroprotective properties. This study focused on the cognitive-enhancing effects of Cyperus esculentus peptide (CEP) based on ‘in silico-drosophila-mice’ stepwise cognitive impairment models, followed by systematical elucidation in multi-target mechanism of its function. Specifically, network pharmacology prediction indicated that CEP exerted the modifying effects through essential nodes including cAMP signaling pathways and neuroinflammation regulation. Behavioral experiments confirmed that CEP effectively enhanced learning and memory capability of stress-modeled fruit flies and scopolamine-induced cognitive impairment mice. Then, mechanism investigation indicated that CEP could activate the cAMP-PKA-CREB-BDNF signaling axis within the central nervous system, enhancing synaptic plasticity (upregulated PSD-95 expression) while concurrently alleviating oxidative stress, cholinergic imbalance, and neuroinflammation. Additionally, CEP remodeled gut microbiota ecology, increasing beneficial bacteria abundance such as Akkermansia and Bifidobacterium and substantially enhancing short-chain fatty acid (SCFA) production. This further activated FFAR2/3 receptor signaling, restored intestinal barrier integrity and suppressed peripheral inflammation, indicating a neuroprotective pathway via the microbiota-gut-brain axis. Conclusively, this study confirmed CEP as a highly promising cognitive enhancer in a synergistic mode of coordinated regulation of central nervous and peripheral pathways, which provided theoretical underpinnings for intervention strategies of bioactive peptides in Cyperus esculentus targeting neurodegenerative diseases via the gut-brain axis.
✓ 已验证
DOI
高影响因子
CELLULAR SIGNALLING
·
2023
·
IF 4.8
Hairong Xiong,Jiaxin Ye,Qianqian Luo,Wen Li,Ning Xu,Hongmei Yang
Cancer cachexia is a systemic inflammation-driven syndrome, characterized by muscle atrophy and adipose tissue wasting, with progressive weight loss leading to serious impairment of physiological function. Extracellular vesicles (EVs) derived from cancer cells play a significant role in adipocyte lipolysis, yet the mechanism remain uneclucidated. In this study, EVs derived from Lewis lung carcinoma (LLC) cells were extracted and characterized. 3 T3-L1 and HIB1B adipocytes were cultured with conditioned medium or EVs from LLC, and LLC cells were used to establish a cancer cachexia mouse model. EVs derived from LLC cells were taken up by 3 T3-L1 and HIB1B adipocytes, and derived exosomal EIF5A protein-induced lipolysis of adipocytes. High level of EIF5A was expressed in EVs from LLC cells, exosomal EIF5A is linked to lipid metabolism. Elevated expression of EIF5A is associated with shorter overall survival in lung cancer patients. Western blots, glycerol release and Oil red O staining assays were used to evaluate lipolysis of adipocytes. The reduction of lipolysis in 3 T3-L1 and HIB1B adipocytes is achieved through silencing EIF5A or treating with pharmacologic inhibitor GC7 in vitro, and suppressing the expression of EIF5A in LLC cells by infected with shRNA or GC7 treatment partly alleviated white and brown adipose tissue lipolysis in vivo. Mechanistically, EIF5A directly binds with G protein-coupled bile acid receptor 1 (GPBAR1) mRNA to promote its translation and then activates cAMP response element binding protein (CREB) signaling pathway to induce lipolysis. This study demonstrates that exosomal EIF5A from LLC cells, with hypusinated EIF5A, has a lipolytic effect on adipocyte and adipose tissues in cancer cachexia model. Exosomal EIF5A could be involved in lipolysis and these findings indicate that a novel regulator and potential target for cachexia treatment.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NEUROSCIENCE
·
2023
·Vol. 58
·期 10
·4123-4136
·
IF 3.4
Hong Ni,Zhongzhao Guo,Yue Wu,Jie Wang,Yang Yang,Zilu Zhu,Deheng Wang
It is generally accepted that Cyclooxygenase-2 (COX-2) is activated to cause inflammation. However, COX-2 is also constitutively expressed at the postsynaptic dendrites and excitatory terminals of the cortical and spinal cord neurons. Although some evidence suggests that COX-2 release during neuronal signalling may be pivotal for regulating the function of memory, the significance of constitutively expressed COX-2 in neuron is still unclear. This research aims to discover the role of COX-2 in memory beyond neuroinflammation and to determine whether the inhibition of COX-2 can cause cognitive dysfunction by influencing dendritic plasticity and its underlying mechanism. We found COX-2 gene knockout (KO) could significantly impact the learning and memory ability, cause neuronal structure disorder and influence gamma oscillations. These might be mediated by the inhibition of prostaglandin (PG) E2/cAMP pathway and phosphorylated protein kinase A (p-PKA)-phosphorylated cAMP response element binding protein (p-CREB)-brain derived neurotrophic factor (BDNF) axis. It suggested COX-2 might play a critical role in learning, regulating neuronal structure and gamma oscillations in the hippocampus CA1 by regulating COX-2/BDNF signalling pathway.
研究领域:
神经科学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2024
·
IF 45.5
Jinjia Zhang,Junhong Li,Yongqiang Hou,Yao Lin,Hao Zhao,Yiran Shi,Kaiyun Chen,Cheng Nian,Jiayu Tang,Lei Pan,Yunzhi Xing,Huan Gao,Bingying Yang,Zengfang Song,Yao Cheng,Yue Liu,Min Sun,Yueyue Linghu,Jiaxin Li,Haitao Huang,Zhangjian Lai,Zhien Zhou,Zifeng Li,Xiufeng Sun,Qinghua Chen,Dongxue Su,Wengang Li,Zhihai Peng,Pingguo Liu,Wei Chen,Hongling Huang,Yixin Chen,Bailong Xiao,Lilin Ye,Lanfen Chen,Dawang Zhou
Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8 + T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8 + T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8 + T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8 + T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8 + T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8 + T cell exhaustion and could be targeted to potentiate cancer immunotherapy.
研究领域:
免疫学
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癌症生物学
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细胞生物学
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转录调控
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产品关联
DOI
PubMed
高影响因子
CANCER RESEARCH
·
2025
·
IF 16.6
Ding Wen,Zhu Jianzheng,Mo Jianshan,Ouyang Shumin,Liu Guopin,Su Yingxue,Sun Danyuan,Ye Jiangling,Wu Yanle,Yan Jiayu,Xue Menghan,Yue Peibin,Lu Jin-jian,Wang Libin,Wang Yandong,Zhang Xiaolei
Small cell lung cancer (SCLC) is a highly aggressive malignancy with limited therapeutic options. Neuroendocrine differentiation is a prominent feature of SCLC. This study identified VGF, a secreted neuropeptide precursor, as a critical regulator of neuroendocrine differentiation in SCLC, particularly the ASCL1+ subtype. VGF orchestrated upregulation of the transcription factor ASCL1 through a CREB-dependent mechanism, thereby promoting neuroendocrine differentiation. Furthermore, VGF mediated the transformation of fibroblasts into cancer-associated fibroblasts (CAFs), establishing metabolic coupling between SCLC cells and CAFs via lactate exchange. A therapeutic strategy targeting VGF and monocarboxylate transporter 1 (MCT-1) disrupted neuroendocrine differentiation and SCLC-CAF metabolic coupling, demonstrating significant efficacy in both in vitro and in vivo models. Together, this study provides insights into the mechanisms underlying SCLC neuroendocrine differentiation and reveals targets and therapeutic strategies for advanced SCLC.
研究领域:
癌症生物学
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分子生物学
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神经生物学
·
细胞信号传导
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肿瘤微环境
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代谢调控
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2024
·
IF 2.8
Fang Liang,Cheng Hongyan,Chen Weidong,Peng Can,Liu Yuanxu,Zhang Caiyun
ObjectivesThe aim of this study was to investigate the therapeutic effects and related mechanisms of Tanshinone IIA and Tetramethylpyrazine O/W composite nanoemulsions on Alzheimer’s disease (AD) rats.MethodsThe therapeutic effect of TSN/TMP O/W NEs on AD rats was evaluated by behavioral tests, H&E, Nissl, and Immunohistochemistry staining. ELISA and Western blot were used to analyze the mechanism.Key findingsThe results showed that TSN/TMP O/W NEs could down-regulate the expression of Bax and Caspase-3 proteins, decrease the level of MDA, increase the expression of SOD and GSH-Px, and alleviate cognitive impairment in AD rats.ConclusionsTSN/TMP O/W NEs can inhibit MAPK/ERK/CREB signaling pathway and effectively alleviate cognitive impairment, oxidative stress injury, and neuronal apoptosis in AD rats.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neuroscience Bulletin
·
2019
·Vol. 35
·期 4
·661-672
·
IF 4.246
Li Yang,Liu Jing,Liu Xu,Su Cun-Jin,Zhang Qi-Lin,Wang Zhi-Hong,Cao Lei-Fang,Guo Xue-Yan,Huang Ya,Luo Weifeng,Liu Tong
The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on depression-like behaviors in mice and to explore the potential mechanisms. These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naïve and space-restriction-stressed (SRS) mice, reflected by a decreased duration of immobility in behavioral despair tests. BoNT/A significantly increased the 5-hydroxytryptamine (5-HT) levels in several brain regions, including the hippocampus and hypothalamus, in SRS mice. BoNT/A increased the expression of the N-methyl-D-aspartate receptor subunits NR1 and NR2B in the hippocampus, which were significantly decreased in SRS mice. Furthermore, BoNT/A significantly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which were decreased in SRS mice. Finally, BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP-response element binding protein (p-CREB), which were suppressed in the hippocampus of SRS mice. Collectively, these results demonstrated that BoNT/A treatment has anti-depressant-like activity in mice, and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus, supporting further investigation of BoNT/A therapy in depression.
研究领域:
神经科学
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精神病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2022
·
IF 3.889
Zhongmei He,He Yu,Hong Wu,Lili Su,Kun Shi,Yan Zhao,Ying Zong,Weijia Chen,Rui Du
Context Fibraurea recisa Pierre. (Menispermaceae) (FR) is a traditional Chinese medicine known as “Huangteng.” The total alkaloids of FR (AFR) are the main active ingredients. However, the pharmacological effects of AFR in the treatment of depression have not been reported.Objectives This study investigates the antidepressant effects of AFR by network pharmacology and verification experiments.Materials and methods Compound-Target-Pathway (C-P-T) network of FR and depression was constructed through network pharmacology. In vitro, HT-22 cells were treated with corticosterone (CORT) solution (0.35 mg/mL), then AFR (0.05 mg/mL) solution and inhibitor AZD6244 (14 μM/mL) or BAY11-7082 (10 μM/mL) were added, respectively. The cell viability was detected by CCK-8. In vivo, C57BL/6 mice were divided into 5 groups, namely the normal group, the CUMS group, the AFR (400 mg/kg) group, and the 2 groups that were simultaneously administered the inhibitory group AZD6244 (8 mg/kg) and BAY11-7082 (5 mg/kg). Western blotting was used to assess the expression level of the proteins.Results AFR could protect HT-22 cells from CORT-induced damage and increase the cell viability from 49.12 ± 3.4% to 87.26 ± 1.5%. Moreover, AFR significantly increased the levels of BDNF (1.3, 1.4-fold), p-ERK (1.4, 1.2-fold) and p-CERB (1.6, 1.3-fold), and decreased the levels of NLRP3 (11.3%, 31.6%), ASC (19.2%, 34.2%) and caspase-1 (18.0%, 27.6%) in HT-22 cells and the hippocampus, respectively.Discussion and conclusions AFR can improve depressive-like behaviours and can develop drugs for depression treatment. Further studies are needed to validate its potential in clinical medicine.
研究领域:
药理学
·
神经科学
·
中医药
✓ 已验证
DOI
PubMed
高影响因子
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