FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Duoduo Zhang,Kunying Chen,Yongkang Yu,Ruting Feng,Steve W. Cui,Xingtao Zhou,Shaoping Nie
Metabolites of dietary fibers which consist of non-digestible carbohydrates (usually as plant-based polysaccharides) exert many benefits on gastrointestinal health. Previous studies proved that polysaccharides can change intestinal metabolic pathways, increase metabolite levels and alleviate intestinal inflammation. Our previous studies have shown that polysaccharide from Aloe vera gel (AGP) alleviated intestinal barrier dysfunction. However, whether intestinal protective function of AGP was related to metabolites need further exploration. Therefore, the effects of AGP on intestinal metabolites and the relevant mechanisms for subsequent mitigation of intestinal damage was investigated in this work. Metabolomics analysis results showed that AGP promoted tryptophan metabolism to 5-hydroxytryptamine (5-HT). Intriguingly, antibiotics treatment decreased the expression of tryptophan hydroxylase 1 (TPH1) in the intestinal epithelium of mice, and TPH1 inhibitor (PCPA) down-regulated 5-HT level in colonic contents, proving that AGP up-regulated TPH1 expression in the intestinal epithelium by restoring intestinal microbiota homeostasis, thus promoted the intestinal tryptophan metabolism to 5-HT. Combination of bioinformatics analysis of RNA-sequencing (RNA-Seq) in mice colon and the reported relationship among “5-HT, Htr4 (one of the 5-HT receptors), Kit + goblet cells, canonical Wnt pathway and intestinal stem cells (ISCs)” guided the confirmation of related mechanism in intestinal organoids (IOs) that 5-HT regulated ISCs function and intestinal barrier via Htr4-Kit-Wnt3 axis. Overall, AGP promoted 5-HT production to alleviate intestinal injury. This study revealed the effects of polysaccharides on intestinal health, which was critical and may provide new insights for the reasonable selection of dietary fiber to prevent intestinal inflammation and maintain intestinal function.
研究领域:
胃肠病学
·
营养学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Yulong Chen,Qingzhou Cheng,Shan Zeng,Site Lv
Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine. Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug. Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2 nm, 45.1 ± 6.2 mV) had a well-defined spherical shape with prolonged drug release and good storage within 4 weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15 μg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104 mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104 mg/kg) group. Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.
研究领域:
药理学
·
纳米技术
·
神经科学
·
植物药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2021
·
IF 5.194
Jing Guan,Xin Tong,Yi Zhang,Fan Xu,Yuxin Zhang,Xiurui Liang,Jiaqi Jin,Hongyan Jing,Liuxian Guo,Xinrui Ni,Jihua Fu
As a widely used anticancer drug in the clinic, cisplatin has obvious side effects, especially nephrotoxicity . Previous studies have suggested that the accumulation of intracellular reactive oxygen species (ROS) is a hallmark of cisplatin-induced acute kidney injury . This study aimed to investigate the relationship between ROS accumulation induced by cisplatin and 5-HT degradation. In vivo, by HE and TUNEL staining, we found that cisplatin-induced renal lesions and apoptotic regions, which were located in proximal tubular epithelial cells, were also the regions in which tryptophan hydroxylase 1 (Tph1), aromatic l -amino acid decarboxylase (AADC), 5-HT 2A receptor (5-HT 2A R) and monoamine oxidase A (MAO-A) were overexpressed, as determined by immunohistochemistry. Notably, the 5-HT 2A R antagonist sarpogrelate hydrochloride (SH) and the AADC inhibitor carbidopa (CDP) significantly attenuated cisplatin-induced increases in serum creatinine and blood urea nitrogen levels, renal ROS levels, oxidative stress (SOD activity and MDA), proinflammatory cytokine levels (NF-κB, TNF-α and IL-1β), proapoptotic factor levels (Bax, Bcl-2, C-caspase 3 and C-caspase 9) and the phosphorylation of p38 and STAT3 , as well as renal lesions and apoptosis . The combination of SH and CDP could almost abolish the effects of cisplatin challenge. In vitro, the effects of cisplatin challenge and the inhibitory effects of SH and CDP were also observed in HK-2 cells. Additionally, similar to the combination of SH and CDP, the MAO-A inhibitor clorgyline could also abolish the effects of cisplatin challenge. More importantly, by western blotting , we detected that the upregulation of Tph1, AADC and MAO-A expression induced by cisplatin both in vivo and in vitro could be obviously suppressed by SH to decrease 5-HT synthesis and mitochondrial 5-HT degradation. Altogether, these findings suggested that cisplatin-induced nephrotoxicity is due to the activation of the 5-HT degradation system in proximal tubular epithelial cells, including 5-HT 2A R and 5-HT synthesis and degradation. 5-HT 2A R plays a role by mediating the expression of MAO-A and the 5-HT synthases Tph1 and AADC.
研究领域:
药理学
·
肾病学
·
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Pan Chen,Hongliang Yao,Weiwei Su,Yudong He,Keling Cheng,Yonggang Wang,Wei Peng,Peibo Li
Aims Sleep deficiency has been reported to be associated with some oral health problems. Oral ulcers are very common lesions of the oral mucosa, which severely impact patients' quality of life. However, the association between sleep deficiency and the oral ulcer remains unknown. The present study aims to explore the effects of sleep deficiency on oral ulcers. Main methods Rats were divided into normal control group (n = 30) and oral ulcer group (OU group, n = 50). Model rats with phenol-induced oral ulcers were deprived of sleep for 72 h by using the modified multiple platform technique. Key findings Sleep deprivation worsened oral ulcers and delayed healing process in rats. In addition, sleep deprivation increased the γ-aminobutyric acid (GABA, P < 0.01) and 5-hydroxytryptamine (5-HT, P < 0.05) levels in serum and brain, the corticotrophin (ACTH, P < 0.05), corticosterone (CORT, P < 0.01), immunoglobulin (Ig)M ( P < 0.01), tumor necrosis factor-alpha (TNF-α) ( P < 0.01), interleukin (IL)-1β ( P < 0.01), IL-6 ( P < 0.01), IL-8 ( P < 0.01), monocyte chemoattractant protein-1 (MCP-1) ( P < 0.01), and 8-hydroxy-deoxyguanosine (8-OHdG, P < 0.01) levels in serum. Sleep deprivation also up-regulated malonaldehyde (MDA) ( P < 0.05), TNF-α ( P < 0.05), and IL-1β ( P < 0.01) levels in oral mucosa tissue and delayed superoxide dismutase (SOD, P < 0.05) activity recovery. Significance These data suggest that sleep deprivation impaired the oral ulcer healing in rat oral mucosa, and the mechanisms of this effect are probably related to neuro-immuno-endocrine system and oxidative stress.
研究领域:
神经科学
·
免疫学
·
内分泌学
·
口腔健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2021
·
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
·
药理学
·
分子生物学
·
转录组学
·
行为科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）