MOLECULAR NUTRITION & FOOD RESEARCH
·
2015
·Vol. 59
·期 8
·1482-1490
·
IF 4.603
Dapeng Chen,Yongjian Xiong,Yuan Lin,Zeyao Tang,Jingyu Wang,Li Wang,Jihong Yao
Scope Capsaicin is an active component of chili peppers, having diverse effects. However, the effects of capsaicin on intestinal motility are still controversial. The present study aimed to investigate the effects of capsaicin on intestinal motility disorder and uncover related mechanisms. Materials and results A rat model with intestinal motility disorder was established in vitro through adding different stimuli into tissue bath; in vivo using constipation and diarrhea model, respectively. Capsaicin exerted dual effects on intestinal motility, i.e. the relaxation and contraction of jejunum induced by corresponding stimulus were, respectively, regulated to be normal contraction by capsaicin. The mechanisms underlined capsaicin-induced dual effects were investigated using Western blotting, qRT-PCR, and whole-cell patch clamp, respectively. Results showed that cholinergic excitatory nerves, adrenergic nerves, and neurons containing nitric oxide synthase, which are the main muscle motor neurons in enteric nervous system (ENS), are involved in capsaicin-induced dual effects. The competition for regulation of Ca 2+ influx by capsaicin induced the interaction with components of the ENS. Capsaicin significantly increased myosin light chain kinase (MLCK) expression and myosin phosphorylation extent in jejunal segments of constipation-prominent rats and significantly decreased MLCK expression and myosin phosphorylation extent in jejunal segments of diarrhea-prominent rats. Conclusion In summary, capsaicin alleviates abnormal intestinal motility through regulating enteric motor neurons and MLCK activity, which is beneficial for the treatment of gastrointestinal motility disorders.
研究领域:
药理学
·
胃肠病学
·
神经科学
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DOI
PubMed
高影响因子
BIOGERONTOLOGY
·
2024
·
IF 4.4
Yuan Qianhua,Luo Mengliu,Xie Yutong,Song Wanhan,Wang Ya,Deng Dazhang,Chen Shuyan,Guo Honghui
Aging entails the progressive decline in the body’s self-regulation and functionality over time. Notably, obesity and aging exhibit parallel phenotypes, with obesity further accelerating the aging process across multiple dimensions and diminishing lifespan. In this study, we explored the impact of trans fatty acid (TFA) consumption on the overall health and lifespan of male Drosophila melanogaster under an isocaloric high-sugar and high-fat diet. Our results indicate that TFA intake results in a shortened lifespan, elevated body weight, and increased triglyceride levels in flies fed a high-sugar and high-fat diet with equivalent caloric intake. Additionally, TFA exposure induces oxidative stress, locomotor deficits, and damage to the intestinal barrier in flies. Collectively, chronic TFA consumption expedites the aging process and reduces the lifespan of male Drosophila melanogaster . These results contribute supplementary evidence regarding the adverse health effects associated with TFAs. Graphical Abstract Trans fatty acid intake results in a shortened lifespan, elevated body weight, and increased triglyceride levels in male Drosophila melanogaster fed a high-sugar and high-fat diet with equivalent caloric intake. Additionally, Trans fatty acid exposure induces oxidative stress, locomotor deficits, and damage to the intestinal barrier in flies.
研究领域:
营养学
·
衰老
·
代谢
·
果蝇遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
·
2022
·Vol. 38
·期 12
·1-14
·
IF 4.253
Wang Ju,Yin Lifen,Zheng Wenxiu,Shi Shengnan,Hao Wenzhuo,Liu Changhong,Zheng Lei
Intestinal peristalsis is essential for gastrointestinal function, which could maintain the appropriate progression and digestion of food and reduce bacterial aggregation through mixing function. Even though certain ingredients of foodstuff are known to increase or decrease intestinal peristalsis, the role of environmental pollutants on intestinal peristalsis is relatively unknown. Therefore, the effects of four typical environmental pollutants (oxytetracycline, arsenic, polychlorinated biphenyls and chlorpyrifos) on intestinal peristalsis in the zebrafish model and then tested the recovery effect of the constipation-resistant probiotic. The results showed that 4-day environmental pollutants exposures on the zebrafish embryos at 1 day post fertilization clearly decreased the intestinal peristalsis through decreasing the serotonin (5-HT) production and down-regulating the expression of key genes involved in 5-HT synthesis. Pollutants-evoked change of gut motility could be normalized in the presence of Lactobacillus rhamnosus GG (LGG) via increasing 5-HT secretion. Exogenous 5-hydroxytryptophan (100 µg/L) could also rescue the dysfunction of gut motility in pollutants-treated zebrfish. The data identified that LGG normalized disorder of intestinal peristalsis induced by environmental pollutants through increasing 5-HT level. The stimulant effect of LGG on peristalsis may be associated with 5-HT system, which could provide references for the application of probiotics in regulation of gut dysmotility. Graphical abstract
研究领域:
环境毒理学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2018
·Vol. 234
·期 4
·4291-4301
·
IF 3.923
Meng-Juan Lin,Lei Chen,Zhen-Peng Huang,Hu Qiu,Bao-Ping Yu
Acute cholecystitis is a common disease with gallbladder dysmotility. Disease pathogenesis involves immune cell infiltration as well as changes in gallbladder interstitial Cajal-like cells (ICLCs). However, it remains unclear if or how the immune cells affect ICLC morphology, density, distribution, and function in gallbladder tissue during acute cholecystitis. In this study, we explored the acute cholecystitis-related alterations in gallbladder ICLCs in a guinea pig model, focusing on the effects of neighboring neutrophils. Adult guinea pigs were randomly divided into four groups (control, 24 hr common bile duct ligation [CBDL], 48-hr CBDL, and antipolymorphonuclear neutrophil [PMN] treated) and analyzed using methylene blue staining and immunofluorescence. Gallbladder contractility was also monitored. To culture gallbladder ICLCs, collagenase digestion was performed on tissue from 10- to 15-day-old guinea pigs. Neutrophils isolated from the peripheral blood of experimental animals 48-hr postsurgery were also cocultured with the gallbladder ICLCs. Intracellular calcium was detected with Fluo-4 AM dye. Our results showed that gallbladder ICLC density significantly declined during acute cholecystitis and was accompanied by shortening of the cellular processes and damage to their network-like structure. However, pretreatment with anti-PMN partially prevented these changes. Gallbladder contraction was also significantly decreased during acute cholecystitis, and this appeared to be mediated by the neutrophils. Moreover, ICLCs cocultured with neutrophils also had shortened and reduced processes and impaired network-like structure formation. Intracellular calcium transient was less sensitive to contraction agonists and inhibitors when cocultured with neutrophils. Taken together, neutrophils greatly affect gallbladder ICLCs and dysmotility during acute cholecystitis.
研究领域:
胃肠病学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Research
·
2023
·
IF 11
Chu Tong,Peng-Xiang Min,Qian Zhang,Ru-Xin Gu,Yao-Hai Wen,Yi Shi,Yu-Huan Bao,Xiang Chen,Yi-Xuan Zhang,Xing-Feng Mao,Hao-Yang Yuan,Xiu-Xiu Liu,Takuya Sasaki,Li Zhang,Feng Han,Ying-Mei Lu
Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like behaviors. However, the molecular mechanisms underlying this disturbance remain elusive. Here, we showed that cyclin-dependent kinase 5 (Cdk5) was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing analysis. Serum levels of CDK5 also decreased in patients with Parkinson’s disease accompanied by motor symptoms. Moreover, Cdk5 deficiency in cholinergic neurons triggered paw tremors, abnormal motor coordination, and motor balance deficits in mice. These symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca2+-activated K+ channels (BK channels). Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient mice. Furthermore, CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of threonine-908. Restoration of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5f/f mice. Together, these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuron-mediated motor function, providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Jiawen Ji,Jinze Huang,Niannian Cao,Xianghong Hao,Yanhua Wu,Yongqiang Ma,Dong An,Sen Pang,Xuefeng Li
The typical tire manufacturing additive 6PPD, its metabolites 6PPDQ and 4-Hydroxy should be monitored because of their ubiquitous presence in the environment and the high toxicity of 6PPDQ to coho salmon. The toxic effect of 6PPD and its metabolites have been revealed superficially, especially on behavioral characteristics. However, the behavioral indicators explored so far are relatively simple and the toxic causes are poorly understood. With this in mind, our work investigated the toxic effects of 6PPD, 6PPDQ and 4-Hydroxy on adult zebrafish penetratingly through machine vision, and the meandering, body angle, top time and 3D trajectory are used for the first time to show the abnormal behaviors induced by 6PPD and its metabolites. Moreover, neurotransmitter changes in the zebrafish brain were measured to explore the causes of abnormal behavior. The results showed that high-dose treatment of 6PPD reduced the velocity by 42.4% and decreased the time at the top of the tank by 91.0%, suggesting significant activity inhibition and anxiety. In addition, γ-aminobutyric acid and acetylcholine were significantly impacted by 6PPD, while dopamine exhibited a slight variation, which can explain the bradykinesia, unbalance and anxiety of zebrafish and presented similar symptoms as Huntingdon's disease. Our study explored new abnormal behaviors of zebrafish induced by 6PPD and its metabolites in detail, and the toxic causes were revealed for the first time by studying the changes of neurotransmitters, thus providing an important reference for further studies of the biological toxicity of 6PPD and its metabolites.
研究领域:
环境毒理学
·
神经科学
·
水生生物学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·
IF 3.8
Si-Chun Gu,Zhi-Guo Xie,Min-Jue Gu,Chang-De Wang,Li-Min Xu,Chen Gao,Xiao-Lei Yuan,You Wu,Yu-Qing Hu,Yang Cao,Qing Ye
Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson’s disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP + ), respectively. Ferroptosis was identified by assessing the levels of Fe 2+ , ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe 2+ , ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP + -induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP + -treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.
研究领域:
神经科学
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药理学
·
细胞生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Kaili Liang,Li Yang,Jiawei Kang,Bo Liu,Ding Zhang,Liyan Wang,Wei Wang,Qing Wang
Parkinson's disease (PD) poses a significant therapeutic challenge, mainly due to the limited ability of drugs to cross the blood-brain barrier (BBB) without undergoing metabolic transformations. Levodopa, a key component of dopamine replacement therapy, effectively enhances dopaminergic activity. However, it encounters obstacles from peripheral decarboxylase, hindering its passage through the BBB. Furthermore, levodopa metabolism generates reactive oxygen species (ROS), exacerbating neuronal damage. Systemic pulsatile dosing further disrupts natural physiological buffering mechanisms. In this investigation, we devised a ROS-responsive levodopa prodrug system capable of releasing the drug and reducing ROS levels in the central nervous system. The prodrug was incorporated within second near-infrared region (NIR-II) gold nanorods (AuNRs) and utilized angiopep-2 (ANG) for targeted delivery across the BBB. The processes of tight junction opening and endocytosis facilitated improved levodopa transport. ROS scavenging helped alleviate neuronal oxidative stress, leading to enhanced behavioral outcomes and reduced oxidative stress levels in a mouse model of PD. Following treatment, the PD mouse model exhibited enhanced flexibility, balance, and spontaneous exploratory activity. This approach successfully alleviated the motor impairments associated with the disease model. Consequently, our strategy, utilizing NIR-Ⅱ AuNRs and ANG-mediated BBB penetration, coupled with the responsive release of levodopa, offers a promising approach for dopamine supplementation and microenvironmental regulation. This system holds substantial potential as an efficient platform for delivering neuroprotective drugs and advancing PD therapy.
研究领域:
神经科学
·
药理学
·
纳米技术
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 20
·10476-10490
·
IF 6.317
Ju Wang,Lei Wang,Shengnan Shi,Yaqi Cao,Junmei Feng,Changhong Liu,Lei Zheng
Probiotic-based therapy is a promising approach, which can positively modulate bacterial composition and maintain homeostasis. However, exogenous probiotics are easily destroyed by harsh conditions in vivo; thus, their application prospects have been severely limited. Specifically, oxytetracycline (OTC), a broad-spectrum antibiotic widely used in aquaculture, results in adverse intestinal environments, such as dysbacteriosis, oxidative damage, and gut dysmotility. Here, we describe a facile method to apply glycol chitosan/alginate as armor on the surface of probiotics to effectively protect them from the changed enteric environments induced by OTC. The results demonstrated that the coated Lacticaseibacillus rhamnosus GG (LGG) for only 2 h administration could significantly improve the colonization rate of LGG, and the relative abundance of Lacticaseibacillus can reach 80% in OTC-treated larvae intestines. We also explored the specific mechanisms of the coated LGG to diminish reactive oxygen species (ROS) generation and rescue gut dysmotility for OTC treatment, including enhancing the activity of antioxidative enzymes (CAT, SOD and GPx) and increasing 5-HT synthesis. The mitigation effect of the coated LGG for 2 h administration was comparable to that of uncoated LGG for 24 h administration. Encapsulation of LGG with polysaccharides provides a unique application example for generating useful bacterial therapeutics in harsh intestinal environments.
研究领域:
水产养殖
·
微生物学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Zhidan Liu,Kang Kang,Shulin Shan,Shuai Wang,Xianjie Li,Hui Yong,Zhengcheng Huang,Yiyu Yang,Zhaoxiong Liu,Yanan Sun,Yao Bai,Fuyong Song
Exposure to carbon disulfide (CS 2 ) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS 2 exposure on parkinsonian pathology. Our results showed that CS 2 exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS 2 induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, in vitro and in vivo experiments demonstrated that the interaction between α-synuclein and the necrosome complex (RIP1, RIP3, and MLKL) is responsible for the loss of neuronal cells after CS 2 exposure. Taken together, our results demonstrate that CS 2 -mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.
研究领域:
神经科学
·
毒理学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Yi Zhao,Yuan-Hang Chang,Hao-Ran Ren,Ming Lou,Fu-Wei Jiang,Jia-Xin Wang,Ming-Shan Chen,Shuo Liu,Yu-Sheng Shi,Hong-Mei Zhu,Jin-Long Li
Di-(2-ethylhexyl) phthalate (DEHP), as the most common phthalate, has been extensively used as a plasticizer to improve the plasticity of agricultural products, which pose severe harm to human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed to explore the effect of DEHP on the nervous system and its association with the ER–mitochondria interaction. Here, we showed that DEHP caused morphological changes, motor deficits, cognitive impairments, and blood–brain barrier disruption in the brain. DEHP triggered ER stress, which is mainly mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results in imbalance of the mitochondrial dynamics. Interestingly, DEHP exposure impaired MAMs by inhibiting the Mfn2-PERK interaction. Above all, this study elucidates the disruption of the Mfn2-PERK axis-mediated ER–mitochondria interaction as a phthalate-induced neurotoxicity that could be potentially developed as a novel therapy for neurological diseases.
研究领域:
神经科学
·
毒理学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Ting Chen,Lan Shou,Xiaowen Guo,Mingyang Wei,Hui Zheng,Tao Tao
In this study, we aimed to investigate the effect of Magnolol on Alzheimer’s disease (AD). After the model of streptozotocin-induced AD mice with brain insulin resistance was established, the mice were treated with Magnolol or miR-200c antagomiR. The abilities of ambulations, rearings, discrimination, spatial learning, and memory were evaluated by open-field test (OFT), novel object recognition (NOR), and morris water maze (MWM) tests. The levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and miR-200c in the mice hippocampus were evaluated by enzyme-linked immunosorbent assay, Western blot, or Quantitative real-time Polymerase Chain Reaction. In AD mice model, streptozotocin induced the locomotor impairment and cognitive deficit, up-regulated levels of MDA, TNF-α, IL-6, and CRP, while down-regulated levels of GSH, SOD, and miR-200c. Magnolol increased the rearings numbers and discrimination index of AD mice in OFT and NOR tests. Magnolol increased the number of entries in the target quadrant and time spent in the target quadrant and decreased the escape latency of AD mice in the MWM test. Magnolol also down-regulated the levels of MDA, TNF-α, IL-6, and CRP, and up-regulated the levels of GSH, SOD, and miR-200c in the hippocampus tissues of AD mice. However, miR-200c antagomiR did the opposite and further offset the effects of the Magnolol on AD mice. Magnolol attenuated the locomotor impairment, cognitive deficit, and neuroinflammatory in AD mice with brain insulin resistance via up-regulating miR-200c.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）