ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Xuanjun Guo,Ruihua Zhang,Qian Jin,Niannian Cao,Jingjing Shi,Xingxing Zong,Xuejun Chen,Chen Wang,Xuefeng Li,Sen Pang,Liqin Li
Azoxystrobin, a strobilurin widely used to control rice diseases, has raised concerns about possible adverse effects on aquatic ecosystems. At present, very little is known about the effects of azoxystrobin on courtship and aggressive behavior and the potential underlying mechanisms. In the present study, after exposing adult male and female zebrafish to worst-case scenario concentrations of azoxystrobin (0, 2 μg/L, 20 μg/L, and 200 μg/L) for 42 d, we observed a decrease in courtship behavior and an increase in aggressive behavior in both male and female zebrafish. In addition, to elucidate the molecular mechanism of the behavioral effects of azoxystrobin, we quantified the changes in the concentrations of kisspeptin, 5-HT, GnIH, and their corresponding receptor mRNA expression in the brain. The results showed that 200 μg/L azoxystrobin decreased the concentrations of kisspeptin and increased the concentration of GnIH in both male and female zebrafish brain. In addition, azoxystrobin also significantly reduced 5-HT concentration in female zebrafish brain. Further investigation revealed that altered courtship and aggressive behavior were associated with the expression levels of genes (kiss1, kiss2, gnrh3, gnrhr3, 5ht1a, and 5ht2a) involved in kisspeptin-GnIH signaling pathway. In conclusion, our study suggested that azoxystrobin may impair courtship and aggressive behavior in zebrafish by interfering with the kisspeptin-GnIH signaling pathway, which may have more profound effects on natural zebrafish populations.
研究领域:
环境毒理学
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行为生物学
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神经内分泌学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 7
·3273
·
IF 4.9
Tianxu Liu,Muyuan Ma,Yonglin Wu,Ismail Muhammad Asif,Daosen Chen,Lichong Liu,Minghui Zhang,Yijie Chen,Bin Li,Ling Wang
As the major polysaccharide in brown algae, fucoidan possesses broad biological abilities and has been reported to improve gastrointestinal health. Functional dyspepsia, a common non-organic disease, is a complex of symptoms mainly characterized by pathogenesis, such as visceral hypersensitivity, gastric dysmotility, and inflammation. To date, the effects of fucoidan in regulating functional dyspepsia with visceral sensitivity remains unclear. In the current study, iodoacetamide was employed to establish a mouse model of visceral hypersensitivity. Meanwhile, fucoidan was orally administrated for fourteen days. Indicators were conducted to evaluate the potential of fucoidan as the ingredient of complementary and alternative medicine for functional dyspepsia, such as levels of serum hormones, expression of receptors, and gut microbial profile. The results show that oral administration of fucoidan led to significant reductions in the secretion of 5-hydroxytryptamine, cortisol, and corticosterone. Additionally, it decreased the expression of 5-hydroxytryptamine-3receptors, with regulation of 5-hydroxytryptamine metabolism and improvement of gut microbial imbalance. The above results suggest fucoidan could ameliorate visceral hypersensitivity by modulating 5-HT metabolism and microbiota. The current findings indicate that fucoidan has potential as a biological component in the adjuvant treatment of functional dyspepsia and for its expanded utilization in the food and medical fields.
研究领域:
胃肠病学
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营养学
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药理学
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PubMed
高影响因子
Translational Pediatrics
·
2025
·Vol. 14
·期 6
·1213
·
IF 1.7
Zihong Shan,Chenghui He,Qingyao Yang,Jingjing Xiong,Meng Li,Mingyao Meng,Yongkun Huang
Background Previous research has indicated that chenodeoxycholic acid (CDCA) plays a significant role in intestinal motility and is implicated in some gastrointestinal (GI) disorders. However, the impact of CDCA on defecation patterns in infants, particularly those who are breastfed, remains unclear. This study explored the relationship between CDCA and defecation frequency in breastfed infants, focusing on the underlying mechanisms. Methods We measured CDCA levels in stool samples of infants with varying defecation frequencies using metabolomics, along with studies to explore the impact of CDCA on murine colonic transit and with in vitro cellular studies to elucidate the underlying physiological mechanisms. Results In our murine model, CDCA treatment increased GI transit distance, enhanced fecal water content, and reduced transit time, without causing significant colonic damage. Additionally, CDCA treatment enhanced 5-hydroxytryptamine (5-HT) secretion and upregulated signaling molecules such as tryptophan hydroxylase 1 (Tph1), G protein-coupled bile acid receptor 1 (TGR5), and transient receptor potential ankyrin 1 (TRPA1). Selective inhibition of these pathways suppressed 5-HT secretion and normalized intestinal motility parameters, confirming their mechanistic role. Moreover, CDCA treatment of rat insulinoma-derived RIN-14B cells also resulted in increased 5-HT secretion. Conclusions These findings reveal that CDCA significantly correlates with defecation frequency in breastfed infants and likely influences intestinal motility through the TGR5/TRPA1-5-HT signaling axis.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2022
·Vol. 414
·期 28
·7967-7976
·
IF 4.478
Jiang Mengyuan,Tian Liang,Su Mengjie,Cao Xiaoqing,Jiang Qiyu,Huo Xiaolei,Yu Chunmei
Serotonin (5-HT) is an essential inhibitory neurotransmitter in vivo that is critical for interneuronal communication of the nervous system. Herein, we constructed an electrochemical cell-sensing platform for 5-HT detection based on MXene/single-walled carbon nanotubes (SWCNTs) nanocomposite. The one-dimensional SWCNTs with good electrical conductivity are uniformly dispersed on the surface and intermediate layers of the two-dimensional MXene to form a tightly heterogeneous heterostructure. The synthesized MXene-SWCNTs could improve the stacking problem of MXene nanosheets and expose more active sites, effectively promoting the conductive properties and electrochemical activity of the composite. The fabricated MXene-SWCNTs/GCE possessed outstanding detection capability for 5-HT with a wide linear range of 4 nM–103.2 μM and a low detection limit of 1.5 nM. Moreover, the sensor was further applied for the real-time monitoring trace amount of 5-HT releasing from different cell lines, which confirmed its promising applications in 5-HT related physiological and pathological fields. Graphical abstract MXene-SWCNTs/GCE was developed and applied for the real-time monitoring of trace amounts of 5-HT secreted from living cells.
研究领域:
神经生物学
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分析化学
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材料科学
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高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Yiming Sun,Hui Cai,Daofeng Yang,Nengyi Yu,Lejie Sun,Jingxuan Xu,Hongwei Yuan,Rong Yang,Lele Song,Hao Liu,Chengyao Ma,Zhe Liu
β-arrestin2 is a versatile protein for signaling transduction in brain physiology and pathology. Herein, we investigated the involvement of β-arrestin2 in pharmacological effects of fluoxetine for depression. A chronic mild stress (CMS) model was established using wild-type (WT) and β-arrestin2 −/− mice. Behavioral results demonstrated that CMS mice showed increased immobility time in the tail suspension test and forced swimming test, elevated concentrations of pro-inflammatory factors in peripheral blood, increased expression of pyroptosis-related proteins, and increased co-labeling of glial fibrillary acidic protein and Caspase1 p10 in the hippocampus compared to the CON group. Treatment with fluoxetine (FLX) ameliorated these conditions. However, compared with the β-arrestin2 −/− CMS group, these results of the β-arrestin2 −/− CMS + FLX group showed no significant changes. These results suggested that the above effects of FLX could be eliminated by knocking out β-arrestin2. Mass spectrometry implying that FLX promoted the binding of β-arrestin2 to the NLRP2 inflammasome of depressed mice. Subsequently, the results of the cellular experiments suggested that the 5HT 2B receptor antagonist may attenuate L-kynurenine + ATP-induced cell pyroptosis by attenuating NLRP2 binding to β-arrestin2. We further found that the lack of β-arrestin2 eliminated the anti-pyroptosis effect of fluoxetine. In conclusion, β-arrestin2 is an essential protein for fluoxetine to alleviate pyroptosis in the hippocampal astrocytes of CMS mice. Mechanistically, we found that the 5-HT 2B R-β-arrestin2-NLRP2 axis is vital for maintaining the antidepressant effects of fluoxetine.
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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行为科学
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高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 9
·1-12
·
IF 5.3
Wang Yanping,Guo Min,Li Yuanyuan,Chen Yan,Wei Hong,Mo Xiaohui,Chai Guolin,Du Yongling,Hu Fangdi
A dual-template molecularly imprinted electrochemical sensor was developed for the simultaneous detection of serotonin (5-HT) and glutamate (Glu). First, amino-functionalized reduced graphene oxide (NRGO) was used as the modification material of a GCE to increase its electrical conductivity and specific surface area, using Glu and 5-HT as dual-template molecules and o-phenylenediamine (OPD) with self-polymerization ability as functional monomers. Through self-assembly and electropolymerization, dual-template molecularly imprinted polymers were formed on the electrode. After removing the templates, the specific recognition binding sites were exposed. The amount of NRGO, polymerization parameters, and elution parameters were further optimized to construct a dual-template molecularly imprinted electrochemical sensor, which can specifically recognize double-target molecules Glu and 5-HT. The differential pulse voltammetry (DPV) technique was used to achieve simultaneous detection of Glu and 5-HT based on their distinct electrochemical activities under specific conditions. The sensor showed a good linear relationship for Glu and 5-HT in the range 1 ~ 100 μM, and the detection limits were 0.067 μM and 0.047 μM ( S / N = 3), respectively. The sensor has good reproducibility, repeatability, and selectivity. It was successfully utilized to simultaneously detect Glu and 5-HT in mouse serum, offering a more dependable foundation for objectively diagnosing and early warning of depression. Additionally, the double signal sensing strategy also provides a new approach for the simultaneous detection of both electroactive and non-electroactive substances.
研究领域:
分析化学
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神经生物学
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医学诊断
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高影响因子
XENOBIOTICA
·
2019
·
IF 1.902
Siyuan Sun,Sisi Zhou,Shaowei Lei,Shujie Zhu,Kai Wang,Huidi Jiang,Hui Zhou
1. Jatrorrhizine is an active ingredient found in various traditional Chinese medicinal plants. Based on our previous finding that jatrorrhizine was a potent inhibitor of OCT2 and OCT3, the aim of the present study was to explore whether jatrorrhizine has an antidepressant-like action action via inhibition of uptake-2 transporters.2. In vitro uptake tests showed that jatrorrhizine strongly inhibited PMAT-mediated MPP+ uptake with an IC50 value of 1.05 μM and reduced 5-HT and NE uptake mediated by hOCT2, hOCT3 and hPMAT with IC50 values of 0.1–1 μM (for OCT2 and OCT3) and 1–10 μM (for PMAT).3. In mouse synaptosomes, jatrorrhizine suppressed 5-HT and NE uptake in a concentration dependently manner, where the role of uptake-2 inhibition is significant.4. The antidepressant-like action of jatrorrhizine was evaluated by mouse tail suspension test (TST). The TST showed that one week of jatrorrhizine (5, 10 and 20 mg/kg, i.p.) or venlafaxine (20 mg/kg, i.g.) can significantly reduce the duration of immobility when compared with vehicle control group.5. The concentration of jatrorrhizine shows a dose-dependent increase in brain tissues.6. Our study suggested that jatrorrhizine might be used as an antidepressant agent via inhibition of uptake-2 transporters.
研究领域:
药理学
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神经科学
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中医药学
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高影响因子
Pharmaceuticals
·
2024
·Vol. 17
·期 9
·1161
·
IF 4.3
Luge Chen,Yingwei Liu,Dawei Xu,Na Zhang,Yong Chen,Jin Yang,Lijuan Sun
With the increasing prevalence of insomnia-related diseases, the effective treatment of insomnia has become an important health research topic. Lavender (Lavandula angustifoliaMill.) essential oil (LEO) is a commonly used medicine for the treatment of insomnia and neurological disorders. However, neither the active components nor its sedative–hypnotic mechanism have been fully discovered. This study aimed to screen the main active terpenes and discover the possible mechanism of LEO through network pharmacology in the treatment of insomnia-related diseases, as well as to verify our hypothesis in insomnia mice. The results showed that, in LEO’s 15 potential active ingredients, beta-myrcene had strong sedative–hypnotic effects through the serotonergic synaptic pathway according to the network pharmacological prediction. Further, PCPA(DL-4-chlorophenylalanine)-induced insomnia mice were treated with beta-myrcene for one day or seven days. The quiet state of insomnia mice was increased effectively, and the hypnotic effect was enhanced by anaobarbital sodium by prolonging sleep duration, decreasing sleep latency, and increasing the rate of falling asleep. Beta-myrcene reduced the damage to hypothalamic neuron cells induced by PCPA and increased neurotransmitter levels of GABA, 5-HT, and Glu in the serum and hypothalamus of insomnia mice. Meanwhile, beta-myrcene exerted an improvement in insomnia by upregulating relevant genes and protein expression in the serotonergic synaptic pathway. These results support the merit of the sedative–hypnotic activity of LEO. Beta-myrcene, a terpene in LEO, may be the main source of its sedative–hypnotic properties. It may serve as a good potential compound in future clinical studies on coping with insomnia.
研究领域:
药理学
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神经科学
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医学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Bojun Chen,Jijun Li,Yuhuan Xie,Xi Ming,Gang Li,Jinjin Wang,Meng Li,Xiaohong Li,Lei Xiong
Ethnopharmacological relevance Cang-ai volatile oil (CAVO) is a traditional Chinese medicine (TCM) inhalational preparation for the treatment of some depressive and emotive disorders. Aim of the study This research aimed to evaluate the efficiency and possible mechanism of intranasal CAVO administration on depression in chronic unpredictable mild stress (CUMS)-induced rats compared to lavender volatile oil (LVO) treatment after CUMS exposure and bilateral olfactory bulb impairment (OBI) in rats. Materials and methods Forty depressive-like model rats induced by CUMS were evaluated by the forced swim test (FST), open field test (OFT), and sucrose preference test (SPT). The model rats were divided into five groups: CUMS (n = 8), CAVOh + CUMS (n = 8), CAVOl + CUMS (n = 8), LVO + CUMS (n = 8), and OBI + CAVO + CUMS (n = 8). The CUMS-induced rats were treated for a period of 4 weeks. The other healthy rats were regarded as the control (CTR, n = 8) subjects. The levels of serotonin (5-HT) and dopamine (DA) and their respective metabolites homovanillic acid (HVA) and 5-hydroxyindol acetic acid (5-HIAA) were measured in brain tissue homogenates of CUMS-induced rats using enzyme-linked immunosorbent assay (ELISA). Results CAVO ameliorated depressive-like behaviors (p < 0.05 ). The levels of DA in the CUMS group were lower than those in the CTR and CAVOh groups (** p < 0.01 and * p < 0.05 ). The levels of HVA were lower in the CUMS group than in the CTR, LVO, OBI + CAVOh and CAVOh groups (** p < 0.01 and * p < 0.05 ) and lower in the OBI + CAVOh group than in the CAVOh group (** p < 0.01 ). The levels of 5-HT in the CUMS group were lower than those in the CTR and CAVOh groups (** p < 0.01 ). The levels of 5-HIAA were lower in the CUMS and OBI + CAVOh groups than in the CTR, LVO and CAVOh groups (** p < 0.01 ). Conclusions CAVO can improve depressive-like behaviors concomitant with the regulation of DA and 5-HT metabolism in the brains of CUMS-induced rats.
研究领域:
药理学
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神经科学
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中医
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高影响因子
NEUROGASTROENTEROLOGY AND MOTILITY
·
2021
·Vol. 33
·期 12
·e14196
·
IF 3.598
Youyou Lu,Junxue Zhang,Xiaohong Zhou,Meiyu Guan,Zhe Zhang,Xi Liang,Lingjun Tong,Huaxi Yi,Pimin Gong,Lu Bai,Hui Zhou,Tongjie Liu,Lanwei Zhang
Background Constipation is a gastrointestinal symptom with high incidence rate and large number of patients. It is becoming one of the urgent medical problems. Poor intestinal motility is one of the important causes of constipation. Current drug treatments for constipation are associated with many side effects; thus, it is necessary to study more effective treatment methods and potential mechanism. Methods A zebrafish model of intestinal motility obstruction was established by loperamide hydrochloride to evaluate the effect of probiotic, food ingredients, and combination on intestinal peristalsis according to intestinal peristalsis frequency counts. The gastrointestinal survival ability of the best probiotics was evaluated by surface hydrophobicity, self-aggregation, acid and bile salt tolerance, and gastrointestinal transit tolerance. Interactions between probiotics and food ingredients were studied in vivo and in vitro. The expression of 5-HT was detected by ELISA and fluorescence immunoassay, and 5-HT related genes were detected by RT-PCR. Key Results We obtained the probiotics, food ingredients, and combination that effectively promoted intestinal peristalsis, X11 and YRL577, P . persica and KGM, KGM + X11, respectively. Both KGM and P . persica promoted colonization of probiotics in vivo. KGM + X11 could effectively promote the increase in 5-HT synthesis in zebrafish via up-regulating gene expression of TPH-1, TPH-2, and 5-HT R and down-regulating gene expression of SERT. The specific in-depth mechanism needs further study. Conclusions and Inferences The combinations of KGM with X11 effectively promoted intestinal peristalsis. We provide a theoretical basis for new modalities that can promote intestinal peristalsis and alleviate constipation.
研究领域:
胃肠病学
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药理学
·
微生物学
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营养学
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高影响因子
NEUROPHARMACOLOGY
·
2026
·
IF 4.7
Huan Gao,Shen Wang,Qi Liu,Jingyi Jia,Yaqi Yang,Zengliang Jin
JZ-1201, targeting SERT, NET, and 5-HT 1A receptors, attenuates depressive-like behaviors. • The antidepressant effect of JZ-1201 is partially mediated by activation of the 5-HT 1A receptor. • JZ-1201 enhances PACAP-related neuroplasticity in the hippocampus. Depression has become a significant public health issue, highlighting the need for novel antidepressants. Based on the monoaminergic mechanisms of classical antidepressant drugs and the therapeutic potential of 5-HT 1A receptor activation, we designed a novel compound, JZ-1201, which acts as a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor and 5-HT 1A receptor partial agonist. This study aimed to evaluate its antidepressant-like effects and explore the underlying mechanisms involving 5-HT 1A receptor activation and enhanced neuroplasticity. The results demonstrated that JZ-1201 exhibited high affinity for the serotonin transporter (SERT) and norepinephrine transporter (NET), and 5-HT 1A receptors, inhibited 5-HT and NE reuptake. It enhanced the 5-hydroxytryptophan (5-HTP)-induced head-twitch response (HTR) and inhibited forskolin-stimulated cAMP formation. In male ICR mice, acute administration of JZ-1201 reduced immobility time in the tail suspension test (TST) and forced swim test (FST), an effect that was attenuated by the selective 5-HT 1A receptor antagonist WAY-100635. Chronic administration of JZ-1201 significantly ameliorated depressive-like behaviors in male Wistar rats subjected to chronic unpredictable mild stress (CUMS). In CUMS rats, JZ-1201 increased dendritic spine density and the expression of PACAP/mTOR/BDNF signaling pathway proteins in the hippocampus. These findings indicate that JZ-1201 is a triple-target antidepressant compound and modulates hippocampal PACAP-related neuroplasticity. Thus, JZ-1201 could be developed as a novel therapeutic agent for the treatment of depression.
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Journal of Functional Foods
·
2026
·
IF 3.9
Li Dong,You Wu,Yangshu Zhou,Hongrong Wang,Lihuai Yu
Menthol is a widely consumed dietary monoterpene found in peppermint oil, yet its effects on intestinal health under inflammatory conditions remain poorly understood. This study investigated the protective effects of dietary menthol against lipopolysaccharide (LPS)-induced intestinal inflammation in a weaned piglet model, focusing on the enteroendocrine Piezo1/TPH1/5-HT signaling axis. Sixty 28-day-old Duroc × (Landrace × Large White) weaned piglets were randomly assigned to five groups: a non-challenged control (CON), an LPS-challenged group, and three LPS-challenged groups receiving menthol at 12.5, 25, or 50 mg/kg of diet in a 22-day trail (21-day feeding +6 h post-LPS). Supplementation with 25 mg/kg menthol of diet significantly increased average daily body weight gain (ADG) and average daily feed intake (ADFI) while reducing the incidence of diarrhea before LPS challenge ( P < 0.05). After LPS administration, menthol markedly attenuated intestinal injury, as evidenced by reduced serum lactate dehydrogenase (LDH) activity and lower levels of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in both serum and intestinal tissues ( P < 0.05). Morphologically, menthol increased villus height and the villus height to crypt depth ratio (VH/CD), decreased crypt depth ( P < 0.05), and preserved microvilli density, tight junction integrity, and nuclear morphology of the small intestine. Notably, menthol partially restored the LPS-induced loss of enteroendocrine cells and normalized gut hormone profiles, specifically reducing serotonin (5-HT) and gastrin while increasing somatostatin. Mechanistically, menthol appeared to suppress the LPS-induced upregulation of the mechanosensor Piezo1, the 5-HT-synthesizing enzyme tryptophan hydroxylase 1 (TPH1), and the 5-HT3 receptor at both the gene and protein levels ( P < 0.05). These findings suggested that dietary menthol, particularly at 25 mg/kg of diet, alleviated intestinal inflammation, potentially by preserving enteroendocrine cell homeostasis and downregulating the Piezo1/TPH1/5-HT signaling pathway. This study provides new evidence for the potential application of menthol as a functional food ingredient to support gut health.
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