COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
·
2019
·
IF 2.142
Rong Xiong,Wei Zhao,Xi Chen,Tian Li,Haiyin Li,Yan Li,Wangshang Shen,Ping Chen
Serotonin is involved in the regulation of many physiological and behavioral processes in vertebrates and invertebrates. The effects of serotonin are mediated through interactions of several 5-HT receptor types. The expression and pharmacological properties of 5-HT1 have received more attention than other serotonin receptors, but its functions at the individual level are little studied in arthropods. Silkworm , a Lepidoptera model, almost has no reports about serotonin receptors. To analyze the function of Bm5-HT1A receptor in vitro , the ORF of Bm5-HT1A was cloned into the pcDNA3.1 vector and expressed in HEK 293 cells . Serotonin activation of Bm5-HT1A -expressing cells decreased forskolin-stimulated cAMP synthesis and had the most potent effect compared to other biogenic amines. Serotonin reduced cAMP synthesis in a dose-dependent manner, and half-maximal activation (EC50) occurred at a concentration of 1.17 × 10 −7 M (117 nM). The pharmacological analysis demonstrated that the rank potency of agonists was pimozide >8-OH-DPAT >5-MeOT ~ αm-5-HT, and antagonists was WAY-100635 > prazosin > SB-269970 > methiothepin at the Bm5-HT1A receptor. Injecting the antagonist of Bm5-HT1A receptor into larvae caused slow or weak motility, and adults lowered courtship vitality or moving speed. Injecting dsRNA of Bm5-HT1A into adults also dropped locomotivity in courtship. These results show that the Bm5-HT1A receptor is related to locomotor activity. This study provides the first information of serotonin receptor on pharmacological in silkworm and on individual functions in arthropods.
研究领域:
神经生物学
·
药理学
·
昆虫生理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 3
·426
·
IF 4.8
Zhimin Song,Meijing Li,Ziwei Zhou,Xiaomeng Guo,Qi Wang,Zekuan Zhang,Keshu Wang,Qixiang Zheng,Wenjing Gou,Sha Wu,Hui Zhao,Muxin Gong
Background:Chronic migraine (CM) is a common complex nervous system disease, often accompanied by symptoms of the digestive tract that interact with each other, leading to prolonged and difficult-to-cure migraines. These symptoms are associated with abnormalities in 5-HT and its receptors. Wuzhuyu decoction (WZYD) is a traditional Chinese medicine prescription commonly used in clinics to treat CM; it relieves gastrointestinal symptoms, such as nausea and vomiting; however, its mechanism is still unclear. Investigating the differences in the role of WZYD compared to existing drugs targeting 5-HT receptors in the treatment of CM not only helps elucidate its pathogenesis but also provides possibilities for the development of new therapeutic approaches.Methods:An inflammation soup (IS)-induced CM male rat model was established. Based on a preliminary experiment, the target of WZYD in treating CM was determined by network pharmacology, and verified by molecular docking. ELISA, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction (RT-qPCR) were used to evaluate the expression levels of CM-related indicators (5-HT, calcitonin gene-related peptide (CGRP), and c-Fos) to ensure the successful establishment of the CM model and the effectiveness of the drug. On this basis, the protein expression levels of 5-HT1A/3A receptors and their cAMP-response element binding protein (CREB) signaling pathway were detected by western blot and immunohistochemistry. The role of 5-HT1A/3A receptors in the treatment of CM by WZYD was validated using a 5-HT1A receptor antagonist (WAY 100635) and a 5-HT3A receptor agonist (SR 57227).Results:The results showed that WZYD increased the expression of 5-HT in the brain, decreased the expression of CGRP, c-Fos, ionized calcium-binding adapter molecule 1 (Iba1), and relieved CM. At the same time, WZYD also increased the expression of the 5-HT1A receptor and decreased the expression of the 5-HT3A receptor in the brain and colon of CM rats. Subsequently, WZYD further exerted its brain-gut integrated therapeutic effects by regulating the CREB signaling pathway mediated by 5-HT1A/3A receptors in the brain and colon of CM rats.Conclusions:WZYD not only regulates neurotransmitters in the brain and colon at the same time, but also specifically regulates 5-HT1A/3A receptors in the brain and colon, which explains the characteristics and advantages of WZYD from a new perspective. While effectively relieving headache symptoms, it also improves related gastrointestinal symptoms, which is more conducive to the treatment of CM.
研究领域:
神经科学
·
药理学
·
中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2024
·
IF 3.7
Liu Yu-Meng,Li Jin-Cao,Gu Yong-Fang,Qiu Ren-Hong,Huang Jia-Ying,Xue Rui,Li Shuo,Zhang Yang,Zhang Kuo,Zhang You-Zhi
Cannabis sativa has been used for improving sleep for long history. Cannabidiol (CBD) has drown much attention as a non-addictive psychoactive component in Cannabis sativa extract. However, the effects of CBD on sleep architecture and it’s acting mechanism remains unclear. In the present study, we evaluated the sedative-hypnotic effect of cannabidiol (CBD), assessed the effects of CBD on sleep using a wireless physiological telemetry system. We further explored the therapeutic effects of CBD using 4-chloro-dl-phenylalanine (PCPA) induced insomnia model and changes in sleep latency, sleep duration and intestinal flora were evaluated. CBD shortened sleep latency and increases sleep duration in both normal and insomnia mice, and those effects were blocked by 5-HT 1A receptor antagonist WAY100635. We determined that CBD increases 5-HT 1A receptors expression and 5-HT content in the hypothalamus of PCPA-pretreated mice and affects tryptophan metabolism in the intestinal flora. These results showed that activation of 5-HT 1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD. This study validated the effects of CBD on sleep and evaluated its potential therapeutic effects on insomnia.
研究领域:
药理学
·
神经科学
·
睡眠医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 51
·30848-30857
·
IF 3.119
Shiben Wang,Lin Qi,Hui Liu,Kang Lei,Xuekun Wang,Renmin Liu
In this study, two series of 1,3,4-oxadiazole derivatives were designed and synthesized using the forced swimming test (FST) model to test the antidepressant activity of the target compound in vivo. Five compounds with potential activity were selected from the FST model to test affinity with 5-HT1A receptor in vitro. The results of the FST experiment showed that compound N-(3-((5-((4-chlorobenzyl)thio)-1,3,4-oxadiazol-2-yl)methoxy)phenyl)acetamide (10g) showed the best antidepressant activity (DID = 58.93, percentage decrease in immobility duration in FST), similar to the activity of positive drug fluoxetine. Compound 10g also exhibited the most potent binding affinity to 5-HT1A receptors (Ki = 1.52 nM). The results of the in vivo 5-HT concentration estimation in mice showed that compound 10g may have an effect on the brain. The experimental results of exploratory activity in mice showed that compound 10g did not affect spontaneous activity in the open-field test model. Molecular docking was used to study the binding mode of compound 10g and the 5-HT1A receptor. Compound 10g showed significant interactions with residues at the active site on the 5-HT1A receptor. The physicochemical and pharmacokinetic properties of the target compounds were predicted using Discovery Studio 2019 and ChemBioDraw Ultra 14.
研究领域:
药理学
·
药物化学
·
神经科学
·
药物发现
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2024
·
IF 2.5
Peipei Feng,Jingyi Chen,Xiaolu Chen,Minghui Tang,Ni Song,Lanyue Zhang,Tinggang He
Delayed treatment of insomnia-related symptoms can harm physical health and increase the psychological burden. In addition to oral medications and some physical therapies, aromatherapy can help overcome some treatment-related side effects. Herein, parachlorophenylalanine (PCPA)-induced insomnia was established in Kunming (KM) mice, which were subjected to aromatherapy using five plants ( Jasminum sambac , Magnolia denudata , Rosa rugosa , Aloysia citriodora , and Abies balsamea ) essential oils (EOs). To determine the sleep-inducing effect of the five EOs, the rate of change in body weight, sleep latency, and total sleep time in mice were measured. Specific serum indices were used to evaluate the therapeutic effects of the tested drugs and PCPA modeling. Gas chromatography-mass spectrometry (GC-MS) was employed to identify active components in EOs. The five EOs contained multiple identical constituents and were rich in terpenoids, such as α-farnesene (28.42%), linalool (68.84%), and citronellol (23.78%). The EOs exhibiting varying effects on insomnia-induced weight loss. Nissl staining was used to examine and the number of neurons was elevated in the EO-treated groups when compared with the PCPA-induced group; however, the neuronal number was reduced in the hypothalamic tissues of the R. rugosa EO (RREO)-treated group. All EOs upregulated the expression of 5-HT1A and GABA A Rα1, as demonstrated by immunohistochemistry, western blotting, and reverse transcription-quantitative PCR results. In addition, EOs of A. citriodora and A. balsamea significantly upregulated the expression of 5HT 1A protein, whereas EOs of J. sambac and M. denudata exerted significantly different effects when compared with the model group, as determined by western blotting.
研究领域:
神经科学
·
药理学
·
植物化学
✓ 已验证
DOI
PubMed
高影响因子
NUTRITIONAL NEUROSCIENCE
·
2026
·
IF 3.1
Dawei Xu,Luge Chen,Xiaohu Chen,Weiming Jiang,Lijuan Sun
Background and Objectives Insomnia is a major public health issue that impairs daily functions and quality of life. Sleep-onset difficulty, a common complaint among patients, is accompanied by reduced central serotonin (5-HT) function. β-myrcene from lavender has sedative–hypnotic effects via serotonergic pathways, but most previous studies used intraperitoneal injection, which causes stress and limits clinical translation. Here, we asked whether non-invasive inhalation of β-myrcene produced similar effects in a mouse model of insomnia with low 5-HT function, and explored the underlying mechanisms.Methods β-myrcene was given to PCPA-induced insomnia mice by inhalation (with intraperitoneal injection as a pharmacodynamic control). In the inhalation group, sleep and behavior were evaluated using the amobarbital sodium sleep test and spontaneous locomotor activity test. ELISA, RT-qPCR, Western blot, and 16S rRNA sequencing were applied to study mechanisms.Results Inhaled β-myrcene shortened sleep latency and prolonged sleep duration. It also reduced oxidative stress and modulated GABA, 5-HT, and glutamate levels. These changes were accompanied by upregulation of mRNAs such as GABAARγ2 and 5-HT1A, as well as proteins including GAD65/67 and PKA, suggesting involvement of 5-HT1A/PKA signaling. Additionally, inhalation of β-myrcene was correlated with alterations in gut microbiota composition in PCPA-induced insomnia mice.Conclusions Our findings indicate that inhaled β-myrcene is associated with sedative–hypnotic effects and alterations in gut microbiota composition in PCPA-induced insomnia mice, potentially involving modulation of 5-HT1A/PKA signaling.
✓ 已验证
DOI
高影响因子
Biomed Research International
·
2019
·
IF 2.197
Yan Chen,Jiongshan Zhang,Mengting Liu,Zengcheng Zou,Fenglin Wang,Hao Hu,Baoguo Sun,Shijun Zhang
Background. Accumulating evidence from prospective epidemiological studies has showed that depression disorder (DD) is a risk factor for cancer. The aim of this study is to explore the association of DD and the overall occurrence risk of hepatocellular carcinoma (HCC) and the mechanism. Methods. In this study, 60 mice were randomly divided into four groups: Control group, DD group, HCC group, HCC-DD group. Mice received a chronic dose of reserpine to establish depression model, followed by Diethylnitrosamine and Carbon tetrachloride administration to establish HCC models. Behavioral depression was assessed by sucrose preference test (SPT) and the expression of Serotonin 1A (5-HT1A) receptor in the hippocampal. The expression of Oatp2a1 and Oatp2b1 in the digestive system tissues was detected by PCR and western blotting. Results. Reserpine-administrated mice had a reducing sucrose preference at Day 14 compared with blank mice (P<0.05). The expression of 5-HT1A receptor in the hippocampal was decreased in DD mice compared with blank mice. The survival analysis indicated that the HCC mice with DD have poorer survival rate compared with the HCC mice. Compared with HCC mice, the expression of Oatp2a1 and Oatp2b1 was lower in liver and stomach tissue and higher in hepatic carcinoma and colon tissue of HCC-DD mice (P<0.05), and the expression of Oatp2a1 was higher in the spleen tissue of HCC-DD mice while the expression of Oatp2b1 was lower (P<0.05). However, no difference was found in the expression of Oatp2a1 and Oatp2b1 in the small intestine tissue between HCC group and HCC-DD group. Conclusions. DD was the adverse factors for the overall occurrence risk of HCC. Mechanistically, be the downregulation of Oatp2a1 and Oatp2b1 in liver tissue induced by DD might be involved.
研究领域:
癌症研究
·
分子生物学
·
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Medicine
·
2024
·
IF 3.1
Zhongzhu Ai,Dongfeng Yuan,Jingyi Cai,Ruotong Dong,Wei Liu,Daonian Zhou
Background: Pruritus ani (PA), a neurofunctional dermatosis, is one of the most common complications of hemorrhoids, which seriously affects the quality of life of patients. Medical hemorrhoid gel (MHG), a product mainly composed of herbal medicine, is widely used for treatment of PA clinically. This study aim to assess the alleviating effect and mechanism of MHG on PA based on rectal epidermis-spinal cord-brain axis using animal models.Methods: A chloroquine-induced mouse itching model and a croton oil preparation-induced rat hemorrhoid model were established to evaluate anti-PA effect of MHG. Scratching behaviors of mice were recorded, and histopathology of mice skin and rat ano-rectal tissues was observed through H&E staining. Network pharmacology and western blotting were employed to explore potential mechanism of MHG.Results: The study indicated that MHG significantly alleviated chloroquine-induced skin itching and improved pathological injuries in mice skin and rat ano-rectal tissues. Network pharmacology suggested that MHG might regulate the JAK/STAT signaling pathway. Experimental findings showed that MHG significantly downregulated TRPV1 and TRPA1 in rectal tissue, c-Fos and GRPR in spinal cord tissue, and 5-HT1a protein in brain tissue, while upregulating TRPM8 protein in rectal tissue. Furthermore, MHG inhibited the activation of the JAK2/STAT3 signaling pathway in the rectal epidermis-spinal cord-brain axis.Conclusion: MHG improves PA by inhibiting the transmission of itching signals in rectal epidermis-spinal cord-brain axis via the JAK2/STAT3 signaling pathway, providing experimental evidence for its clinical application.
研究领域:
药理学
·
神经科学
·
皮肤病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 40
·期 1
·e70278
·
IF 1.7
Junni Fan,Yu Li,Ge Wang,Qian Li,Minfeng Fang
This study employed an affinity chromatography approach to investigate the potential molecular mechanism of the Albiziae Cortex and Polygoni Multiflori Caulis herbal pair, which is commonly used for treating insomnia. Briefly, the haloalkane dehalogenase and its substrate were fused separately onto the serotonin 1A receptor and amino microspheres. Receptors were bound onto chromatographic stationary phases specifically through biological orthogonal interactions. Subsequently, catechin, methyl-O-digalloyl-hexose, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG), and julibroside J 35 were identified as active components in the herbal pair extract targeting the receptor. A mice model of insomnia was used to validate the anti-insomnia effects. The herbal-pair extract, catechin, and THSG significantly reduced sleep latency and increased sleep duration. Furthermore, on-column analysis and molecular docking revealed the binding characteristic. Adsorption isotherm analysis indicated a homogeneous binding process, which was further supported by injection amount-dependent analysis. The latter also provided binding constants of (5.70 ± 0.61) × 10 5 M −1 for catechin and (4.05 ± 0.20) × 10 5 M −1 for THSG. Molecular docking revealed critical binding residues (Asp116, Val117, Thr121, Lys191, Thr196, and Ser199), primarily via van der Waals forces and hydrogen bonds. Collectively, immobilizing the serotonin 1A receptor enables the screening of biologically active compounds from complex systems effectively and shows a degree of general applicability.
研究领域:
生药学
·
天然产物化学
·
神经药理学
·
色谱分析
·
分子对接
✓ 已验证
产品关联
DOI
PubMed
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Essential Oil Bearing Plants
·
2024
·
IF 2.1
Minghui Tang,Yong Ai,Ni Song,Xian Xu,Lin Geng,Dongqiu Chen,Lu Ren,Xiaolu Chen,Jingyi Chen,Lanyue Zhang,Tinggang He
The antidepressant-like effects of five herbal essential oils (EOs), Jasminum sambac (Linn.) Aiton essential oil (JSEOs), Magnolia denudata Desr. essential oil (MDEOs), Rosa rugosa Thunb. essential oil (RREOs), Aloysia citriodora Ortega ex Pers. essential oil (ACEOs) and Abies balsamea (L.) Mill. essential oil (ABEOs) were evaluated. By virtue of a reserpine-induced depression mouse model, the antidepression activities and mechanisms of these EOs were explored. The results indicated that the inhalation of EOs significantly ameliorated depression-like behaviors in reserpine-induced depression mice, including a decrease in anxiety and immobility time. JSEOs and ABEOs significantly attenuated reserpine-induced depression-like behaviors, particularly the decreased body weight and immobility time, as determined by tail suspension and forced swimming tests. Furthermore, RT-qPCR and western blotting analyses indicated that the EOs influenced brain-derived neurotrophic factor (BDNF), serotonin1A (5-HT1A), and inflammatory cytokine levels. ACEOs attenuated reserpine-induced hippocampal and neuronal damage, significantly increased glucocorticoid receptor (GR) and 5-HT1A levels, and suppressed the inflammatory response. These results provide new insights into the antidepressant effects of herbal EOs and suggest that the five EOs evaluated in this study are potential nutraceuticals for the treatment of depression.
研究领域:
药理学
·
神经科学
✓ 已验证
DOI
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2025
·
IF 11.3
Ruobing Bai,Hongyi Xian,Yu Feng,Xiyun Huang,Shiyue Tang,Zhiming Li,Long Zhang,Yizhou Zhong,Wanyan Wu,Jiangpeng Tang,Chudan Gao,Li Yan,Xinguang Zhong,Da Chen,Zhenlie Huang
Hexaphenoxycyclotriphosphazene (HPCTP) has been introduced as a halogen-free replacement for the flame-retardant triphenyl phosphate (TPhP); however, its environmental behavior and toxicological safety remain poorly defined. Here, using zebrafish larvae with TPhP as a benchmark, we systematically evaluated the developmental and neurobehavioral toxicity of HPCTP at environmentally relevant concentrations (50–5000 ng/L) from 6 to 120 h postfertilization. HPCTP showed greater bioaccumulation potential than TPhP, suggesting the risk of long-term ecological persistence. Despite lower acute toxicity, HPCTP induced pronounced developmental defects, including reduced body length and cardiac malformations. Strikingly, HPCTP and TPhP produced divergent neurobehavioral outcomes. HPCTP caused dose-dependent depression-like behaviors (hypoactivity, light-zone avoidance) through suppression of serotonin 1A (5-HT1A) signaling, supported by decreased htr1aa expression and serotonin levels and partially rescued by the 5-HT1A receptor agonist 8-OH-DPAT. By contrast, TPhP elicited anxiety-like phenotypes (hyperactivity, thigmotaxis) via CD83-dependent neuroinflammation, evidenced by decreased cd83 expression and microglial activation, which were reversed by cd83 overexpression. Taken together, these findings demonstrate that HPCTP, though marketed as a safer alternative, poses distinct developmental and neurobehavioral hazards, underscoring the urgent need for comprehensive risk evaluation prior to its widespread application.
研究领域:
环境毒理学
·
发育生物学
·
神经科学
·
分子药理学
·
生态风险评估
✓ 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）