PHYTOMEDICINE
·
2025
·
IF 8.3
Xiaoyun Yun,Jianhui Wu,Jie Zhou,Linlin Song,Yongpei Tang,Hanghong Lo,Jerome P.L. Ng,Menghan Liu,Zhikang Wang,Liqun Qu,Huimiao Wang,Ruilong Zhang,Cairen Wang,Linna Wang,Jiujie Yang,Sookja Kim Chung,Vincent Kam Wai Wong,Betty Yuen Kwan Law
Background Anxiety disorders rank among the most ubiquitous neuropsychiatric disease classifications. Despite their substantial disease burden, the persistent lack of innovative, mechanistically grounded therapeutic interventions over the past two decades highlights an urgent need for novel pharmacological strategies. Purpose The aim of this study is to investigate the neuroprotective and anxiolytic effects of corilagin derived from plant sources, offering novel perspectives for the development of therapeutic strategies targeting anxiety disorders. Methods In this study, high-performance liquid chromatography-mass spectrometry analysis was performed on the crude extract of Phyllanthus emblica Linn. A glutamine-induced cell model and a scopolamine-induced anxiety model were established for in vitro and in vivo investigations, respectively. Anxiety-like behaviors were evaluated using Y-maze, open field tests, and fear conditioning experiments. Laser speckle contrast imaging was employed for relative and qualitative assessment of cerebral blood flow and perfusion in mice. Western blotting, quantitative real-time PCR, and flow cytometry were utilized to elucidate the underlying pathway mechanisms. Finally, RNA sequencing and recombinant adeno-associated virus (AAV)-mediated gene silencing experiments were conducted for target prediction and validation. Results Phyllanthus emblica Linn. derived corilagin showed a strong antioxidant activity in a glutamate-induced cell model. It also inhibited neuronal cell apoptosis caused by oxidative damage, rescued apoptosis from the late stage to the early stage and restored cellular viability. Corilagin alleviated anxiety as reflected by the improvement in scopolamine-induced mice’s behavior such as hyperlocomotion, working memory and emotion memory damage. By applying recombinant AAV-mediated Htr2c silencing shRNA, our findings indicate that corilagin targets the serotonergic system, producing anxiolytic effects by modulating Htr2c to influence 5-HT levels and activate the TrkB/CREB/BDNF pathway in the prefrontal cortex. Compared with the existing fluoxetine anxiolytic drug, this compound demonstrates unique liver-protective properties by downregulating the ALT and AST level. Conclusion This study revealed that corilagin, a bioactive hydrolysable tannin isolated from natural plants, has multiple efficacy in mitigating oxidative and apoptotic damage, alleviating anxiety. The superiority of corilagin as an Htr2c agonist lies in its lower risk of side effects, representing its potential as a novel therapeutic candidate through Htr2c-BDNF signaling modulation, offering a mechanistically innovative approach for both the prevention and clinical management of anxiety disorders.
研究领域:
神经药理学
·
植物药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROENDOCRINOLOGY LETTERS
·
2024
·
IF 0.6
Xiumei Cheng,Xinyi Cao,Yichun Yang,Lingxiao Wang,Yuxuan Yang,Yunjian Pan,Yongliang Zheng,Churong Wei,Yougen Luo
Objective: Methylmercuric chloride (MMC) has neurotoxicity, while hydrogen sulfide (H2S) has shown inhibitory properties against nerve damage induced by various factors. The study aimed to investigate the impact of H2S on MMC-induced learning and memory impairment in mice and to explore the underlying mechanisms. Methods: A mouse model of learning and memory impairment was established by MMC gavage, and sodium hydrosulfide (NaHS) was used as an H2S donor for intervention. Cell viability and live/dead cell ratio in HT22 neuronal cells were assessed by CCK-8 assay and Calcein/PI staining, respectively. The Morris water maze test was performed to evaluate the learning and memory abilities of mice. Western blotting was utilized to determine protein expressions of BDNF and TrkB. The effects of H2S on MMC-induced learning and memory impairment were investigated based on the BDNF/TrkB pathways. Results: (1) MMC treatment decreased cell viability and reduced the ratio of live cells in HT22 cells, while H2S reversed these changes. (2) MMC prolonged escape latency, decreased platform crossing frequency, and reduced quadrant distance percentage of the platform in the Morris water maze test, while H2S reversed the above changes. (3)MMC downregulated BDNF and TrkB expression levels, while H2S suppressed these changes induced by MMC. (4)Treatment with 7, 8-DHF (a TrkB agonist) significantly attenuated MMC-induced prolonged escape latency and reduced platform crossing frequency. Conclusions: Our findings demonstrated that H2S ameliorated learning memory deficits in mice by reversing the inhibitory effects of MMC on BDNF/TrkB signaling pathway.
研究领域:
神经科学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
CNS & Neurological Disorders-Drug Targets
·
2020
·Vol. 19
·期 1
·66-82
·
IF 0
Xianbin Wang,Wei Ma,Tongtong Wang,Jinwei Yang,Zhen Wu,Kuangpin Liu,Yunfei Dai,Chenghao Zang,Wei Liu,Jie Liu,Yu Liang,Jianhui Guo,Liyan Li
Background: Brain-Derived Neurotrophic Factor (BDNF) plays critical roles during development of the central and peripheral nervous systems, as well as in neuronal survival after injury. Although proBDNF induces neuronal apoptosis after injury in vivo, whether it can also act as a death factor in vitro and in vivo under physiological conditions and after nerve injury, as well as its mechanism of inducing apoptosis, is still unclear. Objective: In this study, we investigated the mechanisms by which proBDNF causes apoptosis in sensory neurons and Satellite Glial Cells (SGCs) in Dorsal Root Ganglia (DRG) After Sciatic Nerve Transection (SNT). Methods: SGCs cultures were prepared and a scratch model was established to analyze the role of proBDNF in sensory neurons and SGCs in DRG following SNT. Following treatment with proBDNF antiserum, TUNEL and immunohistochemistry staining were used to detect the expression of Glial Fibrillary Acidic Protein (GFAP) and Calcitonin Gene-Related Peptide (CGRP) in DRG tissue; immunocytochemistry and Cell Counting Kit-8 (CCK8) assay were used to detect GFAP expression and cell viability of SGCs, respectively. RT-qPCR, western blot, and ELISA were used to measure mRNA and protein levels, respectively, of key factors in BDNF-TrkB, proBDNF-p75NTR/sortilin, and apoptosis signaling pathways. Results: proBDNF induced mitochondrial apoptosis of SGCs and neurons by modulating BDNF-TrkB and proBDNF-p75NTR/sortilin signaling pathways. In addition, neuroprotection was achieved by inhibiting the biological activity of endogenous proBDNF protein by injection of anti-proBDNF serum. Furthermore, the anti-proBDNF serum inhibited the activation of SGCs and promoted their proliferation. Conclusion: proBDNF induced apoptosis in SGCs and sensory neurons in DRG following SNT. The proBDNF signaling pathway is a potential novel therapeutic target for reducing sensory neuron and SGCs loss following peripheral nerve injury.
研究领域:
神经生物学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
International Heart Journal
·
2024
·Vol. 65
·期 6
·1095-1106
·
IF 1.2
Xiaoping Zhu,Shengnan Han,Yulu Geng,Wenzhi Ren,Fushi Quan
Stroke poses a serious risk to human health. The incidence of stroke is increasing year by year. In this study, a rat cerebral ischemiareperfusion (middle cerebral artery occlusion) model was established, and the reliability of this model was determined.The expression changes of key proteins of the BDNF TrkB pathway and synaptic plasticity markers (SYP, PSD-95, and MAP-2) were detected at different time points.The results showed that BDNF expression increased rapidly in the acute phase, and the expression of synaptic plasticity markers decreased, and blocking the BDNF-TrkB pathway with the specific blocker K252a also had a significant effect.This suggests that changes in the BDNF-TrkB signaling pathway can affect the synaptic plasticity in nerve cells of stroke patients.
CAS / MDL:
研究领域:
神经科学
·
分子生物学
·
中风研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NUTRITIONAL NEUROSCIENCE
·
2022
·
IF 4.062
Yumin Liu,Ziqi Hu,Jing Wang,Yanjun Liao,Luan Shu
Objective Depression is one of the most common complications in patients with diabetes. Our previous study demonstrated puerarin, a dietary isoflavone, improved glucose homeostasis and β-cell regeneration in high-fat diet (HFD)-induced diabetic mice. Here, we aim to evaluate the potential effect of puerarin on diabetes-induced depression.Methods The co-occurrence of diabetes and depression with related biochemical alterations were confirmed in HFD mice and db/db mice, respectively using behavioral analysis, ELISA and western blotting assay. Furthermore, impacts of puerarin on depression-related symptoms and pathological changes were investigated in HFD mice.Results The results showed that puerarin effectively alleviated the depression-like behaviors of HFD mice, down-regulated serum levels of corticosterone and IL-1β, while up-regulated the content of 5-hydroxytryptamine. Simultaneously, puerarin increased the number of hippocampal neurons in HFD mice, and suppressed the apoptosis of neurons to protect the hippocampal neuroplasticity. GLP-1R expression in hippocampus of HFD mice was enhanced by puerarin, which subsequently activated AMPK, CREB and BDNF/TrkB signaling to improve neuroplasticity. Importantly, our data indicated that puerarin had an advantage over fluoxetine or metformin in treating diabetes-induced depression.Conclusion Taken together, puerarin exerts anti-depressant-like effects on HFD diabetic mice, specifically by improving hippocampal neuroplasticity via GLP-1R/BDNF/TrkB signaling. Puerarin as a dietary supplement might be a potential candidate in intervention of diabetes with comorbid depression.
研究领域:
药理学
·
神经科学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
·
2017
·
IF 2.341
Xiaoyu Song,Bo Liu,Lingyu Cui,Biao Zhou,Weiwei Liu,Fanxing Xu,Toshihiko Hayashi,Shunji Hattori,Yuko Ushiki-Kaku,Shin-ichi Tashiro,Takashi Ikejima
Depression is one of the most frequent psychiatric disorders of Alzheimer's disease (AD). Depression and anxiety are associated with increased risk of developing AD. Silibinin , a flavonoid derived from milk thistle ( Silybum marianum ), has been used as a hepato-protectant in the clinical treatment of liver diseases. In this study, the effect of silibinin on Aβ-induced anxiety/depression-like behaviors in rats was investigated. Silibinin significantly attenuated anxiety/depression-like behaviors caused by Aβ1-42-treatment as shown in tail suspension test (TST), elevated plus maze (EPM) and forced swimming tests (FST). Moreover, silibinin was able to attenuate the neuronal damage in the hippocampus of Aβ1-42-injected rats. Silibinin-treatment up-regulated the function through BDNF/TrkB pathway and attenuated autophagy in the hippocampus. Our study provides a new insight into the protective effects of silibinin in the treatment of anxiety/depression.
研究领域:
神经科学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2023
·
IF 3.8
Lingyu Qin,Junming Wang,Xiaohui Wu,Lingling Song,Yueyue Zhang,Mingzhu Gong,Yanmei Wang,Bingyin Li
ABSTRACT Lonicera japonica flos (LJF) is a common clinical herb with outstanding medicinal and nutritional value. This study aimed to evaluate the antidepressant effects of LJF’s active extract and compound chlorogenic acid (CGA) around BDNF-TrkB pathway. The results showed that LJF extracts and CGA had significant antidepressant effects, and the antidepressant effects of different extracts of LJF was highly positively correlated with the content of CGA (FST, r = 0.998; TST, r = 0.934). Moreover, LJF-70% ethanolic extract and CGA improved CUMS induced depressive behavior, upregulated protein expression levels of BDNF and p -TrkB in the hippocampus, restored the damage of hippocampal neurons, and protect liver from damage. In summary, this study demonstrated for the first time that LJF-70% ethanolic extract was the active extract of LJF antidepressant and CGA was its active antidepressant compound, and the antidepressant mechanism mainly involved the upregulation of BDNF-TrkB signaling pathway in the hippocampus of mice.
研究领域:
药理学
·
神经科学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH
·
2024
·
IF 2.7
Xinliu Wang,Xin Zhang,Wei Xie,Yuanyuan Wang,Shuxian Zang,Ziyun Ban,Depei Li,Yugai Jia,Yonggang Gao
Depression is a common mental illness, which is highly related to intestinal motor dysfunction and causes a global burden of disease. Lindera aggregata (LA), a traditional medicinal herb, has been used to treat gastrointestinal disorders; however, the effect of LA on depression remains unclear. Here, we assessed the impact of LA on chronic unpredictable mild stress (CUMS)-induced depression in mice and explored the related mechanisms. The results showed that LA ameliorated depressive behaviors in mice exposed to CUMS, as evidenced by improved performance in the sucrose preference test, force swimming test, and open field test, as well as increased serum levels of adrenocorticotropic hormone and 5-hydroxytryptamine. In addition, LA increased the serum levels of D-xylose and ghrelin, indicating that LA can promote gastrointestinal motility. Additional studies revealed that LA relieved CUMS-induced hippocampal tissue damage, as shown by hematoxylin and eosin and Nissl staining. LA increased the expression levels of brain-derived neurotrophic factor (BDNF) and promoted the activation of tropomyosin receptor kinase B (TrkB) and cAMP response element-binding (CREB) in the hippocampus of CUMS-exposed mice or in corticosterone-injured HT22 cells. In conclusion, LA can improve CUMS-induced depressive behavior in mice, potentially through hippocampal neuroprotection mediated by the BDNF/TrkB/CREB signaling pathway, which also contributes to improved intestinal function.
研究领域:
药理学
·
神经科学
·
精神病学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neuropsychiatric Disease and Treatment
·
2025
·
IF 2.9
Yueyi Zhang,Qianqian Cai,Lingshan Wang,Bei Zhang
Background & Aims Esketamine, a promising treatment for treatment-resistant depression, has shown potential advantages over traditional antidepressants. However, its mechanisms remain unclear. This study explores how esketamine alleviates depressive behaviors through activation of the BDNF/TrkB/PI3K/AKT signaling pathway.Methods Using a Chronic Unpredictable Mild Stress (CUMS) rat model, behavioral assays (Sucrose Preference Test, Morris Water Maze Test) and histological analyses (HE and Nissl’s staining) were performed. Esketamine (5 mg/kg) treatment was administered to evaluate its antidepressant effects, and the PI3K inhibitor, PI3K-IN-6, was used to investigate the role of the PI3K/AKT pathway in the underlying mechanism.Results Esketamine treatment improved depressive behaviors, enhanced neuronal structure, and reduced apoptosis and oxidative stress. These effects were linked to the activation of the BDNF/TrkB/PI3K/AKT pathway. PI3K-IN-6 reversed the effects, confirming the pathway’s involvement.Conclusion Esketamine alleviates depressive behaviors by activating the BDNF/TrkB/PI3K/AKT signaling pathway, reducing oxidative stress and inhibiting neuronal apoptosis. These findings highlight the therapeutic potential of esketamine in treating depression, particularly in cases where traditional treatments fail.
研究领域:
神经药理学
·
精神病学
·
分子生物学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Fengjiao Liu,Yaxin Jia,Liwei Zhao,Li-na Xiao,Xizhen Cheng,Yingying Xiao,Ying Zhang,Yuling Zhang,Huimin Yu,Qiao-en Deng,Yuanyuan Zhang,Yimeng Feng,junfang Wang,Yonggang Gao,Xuan Zhang,Yunyun Geng
Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10 mg/kg) or fluoxetine (2 mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1β, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.
研究领域:
药理学
·
神经科学
·
精神病学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Wang Guoli,Lei Cong,Tian Ya,Wang Yingping,Zhang Lianxue,Zhang Ronghua
Panax ginseng C.A. Meyer (Araliaceae), a popular tonic and dietetic herbal medicine, has been traditionally prescribed in China and other countries to treat affective disorders. The medicinal parts of ginseng, the roots and flower buds, have become increasingly popular as dietary supplements due to the current holistic healthcare trend. We have investigated for the first time the antidepressive actions of the different medicinal parts, namely, the main roots, fibrous roots, and flower buds (in water extract and powder), of garden-cultivated ginseng through behavioral and drug-induced tests in mice. The water extracts, but not the powders of ginseng fibrous roots, flower buds, and main roots (1.5 g of crude drug per kilogram, p.o.), significantly reduced the immobility time in the forced swim test (FST) and tail suspension test (TST); moreover, the water extracts enhanced the 5-hydroxytryptophan (5-HTP)-induced head-twitch response and antagonized the action of reserpine in the mouse. We then explored the antidepressive mechanism of action of the ginsenoside Rb1 (Rb1) related to the brain-derived neurotrophic factor (BDNF) and its downstream proteins in mice exposed to chronic unpredictable mild stress (CUMS). Treatment with Rb1 (20 mg/kg, p.o.) for 21 days significantly attenuated the CUMS-induced decrease in the activities of BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), extracellular regulatory protein kinase (ERK), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in the mouse hippocampal CA3 region and prefrontal cortex (PFC). Interestingly, treatment with the novel TrkB antagonist ANA-12 (0.5 mg/kg, i.p.) did not alter the level of BDNF but significantly blocked the antidepressive effects of Rb1 on proteins downstream of BDNF in CUMS-treated mice. These results suggest that BDNF–TrkB–CREB signaling may be involved in the antidepressive mechanism of the action of Rb1.
研究领域:
药理学
·
神经科学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Ya-Nan Tang,Yun-Feng Bai,Ai Dong,Qin-Ling Rao,Hong-Hua Wu,Chun-Guo Wang,Yan-Tong Xu
Ethnopharmacological relevance Kai-Xin-San (KXS) is a classic prescription for treating affective disorders in traditional Chinese medicine (TCM) over millennium. Although antidepressant effects of KXS have been demonstrated in both clinical and preclinical studies, antidepressant constituents and action mechanisms of KXS remain unclear. Aim of the study To reveal antidepressant constituents and action mechanisms of KXS using the method of “fraction-spectrum-effect-mechanism”. Materials and methods Homologous fractions of KXS were isolated through solvent extraction combined with macroporous resin chromatography methods. The quantification of the fractions was performed using chemical chromogenic methods. Antidepressant effects of the homologous fractions were assessed using tail suspension test (TST), forced swimming test (FST) and open field test (OFT) in mice. Two major fractions of total phenols (TP) and total saponins (TS) were chosen for further studies. The constituents of TP and TS were identified using UPLC-Q-Exactive Orbitrap-MS (UPLC-MS) method, and their antidepressant effects were verified on chronic restraint stress (CRS) model in mice by behavioral evaluations including sucrose preference test (SPT), TST, FST and OFT. Network pharmacology was used to predict antidepressant mechanisms of TP and TS based on the homologous constituents determined in UPLC-MS analysis. Proteomic analyses were undertaken with tissues of hippocampus (HP) and prefrontal cortex (PFC) in CRS mice treated by TP and TS. Western blot (WB) was employed to verify the findings in network pharmacology and proteomic analyses. Results Five homologous fractions of essential oils (EO), TP, TS, oligosaccharides (OL) and polysaccharides (PO) were isolated from KXS with homologous contents exceeding 50 %. Results of TST and FST indicated that all the five fractions significantly decreased the immobility time of mice, while OFT results exhibited that their locomotor activities remained unchanged. A total of 50 constituents and 114 constituents were identified in the TP and TS, respectively. CRS tests demonstrated that both TP and TS significantly increased the percent of sucrose consumption and decreased the immobility time in the TST and FST, without affecting their locomotor activities. Results of both network pharmacology and proteomic analyses primarily pointed to similar contents highly related to depression. GO analysis on TP and TS principally enriched in synaptic structures and functions, as well as neural metabolic and gene expression processes. KEGG analysis on TP and TS principally enriched in pathways of neurodegeneration-multiple diseases, as well as neurotrophin signaling pathway in HP and PFC. Results of WB verified that TP and TS significantly reversed the decrease in signature proteins of synaptic plasticity including presynaptic SYN1, postsynaptic PSD95 and GRIA1, as well as the underlying mechanism of BDNF/TrkB/Akt pathway in the HP and PFC induced by CRS. Conclusion This is the first study on antidepressant constituents and action mechanisms of KXS guided by the method of “fraction-spectrum-effect-mechanism”. Albeit the findings are still preliminary, it provides an example in methodology for unraveling the complicated chemical system and action mechanisms of TCM prescriptions.
研究领域:
药理学
·
神经科学
·
民族药理学
·
中医药学
·
精神药理学
·
蛋白质组学
·
网络药理学
✓ 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）