JOURNAL OF AFFECTIVE DISORDERS
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2024
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IF 4.9
Aoqi Song,Ru Cheng,Jingjing Jiang,Han Qu,Zhenghua Wu,Feng Qian,Shuyu Shen,Liwen Zhang,Zhiyu Wang,Wenjuan Zhao,Yuefen Lou
Background The antidepressant effect of hyperoside (HYP), which is the main component of Hypericum perforatum , is not established. This study aimed to determine the effects of HYP on depression. Methods The antidepressant-like effect of HYP was studied in mice induced by chronic restraint stress (CRS). The effects of HYP on behavior, inflammation, neurotransmitters, gut microbiota, and short-chain fatty acids (SCFAs) were studied in CRS mice. Results HYP improved depressive-like behavior in mice induced by CRS. Nissl staining analysis showed that HYP improved neuronal damage in CRS mice. Western blot (WB) analysis showed that HYP increased the expression levels of BDNF and PSD95 in the hippocampus of CRS mice. The results of ELISA showed that HYP down-regulated the expression levels of IL-6, IL-1β, TNF-α, and CORT in the hippocampus, blood, and intestinal tissues of mice and up-regulated the expression levels of 5-HT and BDNF. Hematoxylin and eosin (HE) staining results indicate that HYP can improve the intestinal histopathological injury of CRS mice. The results of 16S rRNA demonstrated that HYP attenuated the dysbiosis of the gut microbiota of depressed mice, along with altering the concentration of SCFAs. Limitations In the present study, direct evidence that HYP improves depressive behaviors via gut microbiota and SCFAs is lacking, and only female mice were evaluated, which limits the understanding of the effects of HYP on both sexes. Conclusions HYP can improve CRS-induced depressive-like behaviors in mice, which is associated with regulating the gut microbiota and SCFAs concentration.
研究领域:
药理学
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神经科学
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微生物学
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行为科学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2022
·
IF 6.78
Lei Wang,Jiahui Ma,Wei Wu,Yimeng Fang,Fan Liu,Qinsi Yang,Xiang Hu,Xuejiang Gu,Zhiying He,Da Sun,Libo Jin,Xingxing Zhang
Background Depression is the most known complication of type 2 diabetes mellitus (T2DM). Aerobic exercise improves glycemic control in T2DM, although the underlying mechanisms of comorbid depression-like behaviors in T2DM have not yet been fully elucidated. Methods 120 zebrafish were randomly assigned to four groups: Control, T2DM, T2DM + metformin, and T2DM + aerobic exercise. Then, all animals except the control group were fed with high glucose fairy shrimp (~40 g/kg/day) and exposed reserpine (40 μg/ml for 20 min) for 10 days. Here, behavioral tests were used for model verification. Following the verification, all groups were treated as before. Additionally, the T2DM + metformin group received metformin (~10.6 mg/kg/day) at the same time, while the T2DM + aerobic exercise group received aerobic exercise 30 min/day. Finally, blood glucose and behavioral tests, as well as protein and molecular levels were determined at Day 11 and 12. Results Aerobic exercise alleviated depressive-like behavior and enhanced the levels of antidepressant biomarkers (NE, 5-HIAA) in zebrafish after 10 consecutive days of exercise. Additionally, 10 consecutive days of aerobic exercise decreased the levels of inflammatory biomarkers (IFN-γ, IL-1, IL-4) and depressive biomarkers (cortisol). Meanwhile, it also aided in the reduction of CD11b, IL-6, IL-6R, and caspase-3 expression to combat the neuroinflammation induced by T2DM, mediated the BDNF-TrkB pathway, and increased Bcl-2/Bax levels. Conclusion Given the remarkable similarity in neurochemistry between humans and zebrafish, this study supports the effectiveness of aerobic exercise as clinical guidance in preventing and treating T2DM complicated with depression.
研究领域:
内分泌学
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神经科学
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药理学
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运动科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Xi-Xi Li,Xiu-Yuan Lang,Teng-Teng Ren,Jun Wang,Rongfeng Lan,Xiao-Yan Qin
Ethnopharmacological relevance Tibetan ginseng named Wangla (tuber of Coeloglossum viride var. bracteatum ) is a traditional tonic that has Yang-strengthening and qi-enhancing, tranquilizing, intelligence-enhancing and longevity-enhancing properties. It has been used to treat impotence, spermatorrhea , anemia and insomnia. Therefore, its characteristic components and neuronal modulating effects were studied. Aim of the study: To investigate the elimination of Aβ-induced toxicity by CE and to elucidate the molecular mechanisms involving BDNF , FGF2 , and their related signaling axis, and the RIP1-driven inflammatory pathway. Materials and methods We established Aβ-induced toxicity models in cultured neurons and ICR mice , respectively. MWM and fear conditioning tests were performed for behavioral analysis of cognitive functions in mice. Western blot was used to investigate the levels of BDNF, FGF2, and their downstream effector TrkB/Akt/Bcl-2, as well as the RIP1-driven RIP1/RIP3/MLKL pathway. Immunofluorescence assay is used to examine the status of glial cells. Results CE abrogated Aβ toxicity and inhibited apoptosis in cultured neurons, mainly by regulating the BDNF, FGF2, and TrkB/Akt signaling pathways as well as RIP1-driven inflammation and necroptosis. Similarly, mice injected intracerebrally with Aβ exhibited cognitive deficits and had elevated oxidative stress and inflammatory factors detected in their serum and brain. However, CE-treated mice showed recovery of cognitive abilities and quelled levels of oxidative stress and inflammatory factors. Moreover, Aβ toxicity led to a reduction in BDNF, FGF2, and related signaling regulators in the hippocampus and prefrontal cortex, accompanied by activation of RIP1-driven inflammatory signaling pathways, and a reduction in TBK1 and Bcl-2. However, CE restored the levels of BDNF, FGF2, and TrkB/Akt signaling pathway, while inhibiting RIP1-induced RIP1/RIP3/MLKL pathway, thereby antagonizing apoptosis and maintaining neuronal activity. Conclusions CE effectively eliminated the toxicity of Aβ in cultured neurons and mouse models, which holds promise for drug development .
研究领域:
神经药理学
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民族药理学
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分子生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2022
·Vol. 13
·期 11
·6166-6179
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IF 6.317
Hongxia Li,Xin Xu,Mengyu Cai,Yicui Qu,Zifu Ren,Chuyang Ye,Hui Shen
The aim was to investigate whether the combination of hydroxytyrosol acetate (HT-ac) and ethyl β-hydroxybutyrate (HBET) can improve the cognition of heat-stressed mice, meanwhile exploring the mechanism of action. Mice were divided into 5 groups: control, heat-stressed, HT-ac, HBET, and HT-ac + HBET. Mice were gavaged for 21 days and exposed to heat (42.5 ± 0.5 °C, RH 60 ± 10%, 1 h day-1) on days 15–21, except for the control group. Results showed that the combination of HT-ac + HBET improved the cognitive and learning abilities of heat-stressed mice, which were tested by Morris water maze, shuttle box, and jumping stage tests. The combination of HT-ac + HBET maintained the integrity of neurons and mitochondria of heat-stressed mice. Likewise, this combination increased the mitochondrial membrane potential, the ATP content, the expression of phosphorylated PKA, BDNF, phosphorylated CREB and Bcl-2, and decreased the expression of Bax, caspase-3, and intracytoplasmic Cyt C in heat-stressed mice.
研究领域:
神经科学
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药理学
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生理学
✓ 已验证
DOI
PubMed
高影响因子
NEUROBIOLOGY OF DISEASE
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2024
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IF 5.1
Lu Deng,Hong Jiang,Jingjing Lin,Di Xu,Ailin Qi,Qing Guo,Ping-Ping Li,Xinshi Wang,Judy S. Liu,Xiaoqin Fu,Peijun Li
Summary Epilepsy is a brain disorder affecting up to 1 in 26 individuals. Despite its clinical importance, the molecular mechanisms of epileptogenesis are still far from clarified. Our previous study showed that disruption of Clock in excitatory neurons alters cortical circuits and leads to generation of focal epilepsy. In this study, a GAD-Cre;Clock flox/flox mouse line with conditional Clock gene knockout in inhibitory neurons was established. We observed that seizure latency was prolonged, the severity and mortality of pilocarpine-induced seizure were significantly reduced, and memory was improved in GAD-Cre;Clock flox/flox mice. We hypothesize that mice with CLOCK knockout in inhibitory neurons have increased threshold for seizure, opposite from mice with CLOCK knockout in excitatory neurons. Further investigation showed Clock knockout in inhibitory neurons upregulated the basal protein level of ARC, a synaptic plasticity-associated immediate-early gene product, likely through the BDNF-ERK pathway. Altered basal levels of ARC may play an important role in epileptogenesis after Clock deletion in inhibitory neurons. Although sEPSCs and intrinsic properties of layer 5 pyramidal neurons in the somatosensory cortex exhibit no changes, the spine density increased in apical dendrite of pyramidal neurons in CLOCK knockout group. Our results suggest an underlying mechanism by which the circadian protein CLOCK in inhibitory neurons participates in neuronal activity and regulates the predisposition to epilepsy.
研究领域:
神经科学
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分子生物学
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昼夜节律
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癫痫学
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2024
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IF 4.2
Yang Yang,Yuanji Zhao,Huan Lei,Xiaohong Tan
Purpose When consumed in appropriate quantities, probiotics, which are live microorganisms, are good for health. In this study, a mouse model of antibiotic-induced dyskinesia was established using a sterile mixed antibiotic solution to investigate the preventive impact of Limosilactobacillus fermentum ZS09 (LFZS09) on this condition in mice.Methods Following modeling, alterations in the serum and brain tissue of mice were assessed for motor measures such as running and swimming, malondialdehyde (MDA), superoxide dismutase, reduced glutathione, interleukin (IL-6, IL-10), and tumor necrosis factor (TNF)-α. The mouse cecum was used to evaluate the relative mRNA expression levels of the intestinal barrier genes, namely occludin-1, zona occludens-1 (ZO-1), and claudin-1. The relative mRNA expression levels of cAMP-response element binding protein (CREB), extracellular signal-regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) genes in the mouse brain tissue were also evaluated.Results Compared with the model group, LFZS09 considerably increased the swimming and running duration of mice, significantly decreased the levels of the inflammatory factors TNF-α and IL-6 and increased SOD expression in the mouse brain, and decreased MDA accumulation in the mouse brain and serum. Furthermore, LFZS09 upregulated occludin-1 gene expression in the cecal tissue to maintain the intestinal barrier, which in turn maintained the normal physiological function of the body. LFZS09 also enhanced the effect of BDNF and increased the expression of BDNF metabolic pathway-related genes, namely CREB, ERK1/2, and BDNF, in the mouse brain tissue. LFZS09 increased the number of Lactobacillus and Bifidobacterium in the gut of mice with motor dysregulation, and decreased the number of Enterococcus and Clostridium perfringens.Conclusion The findings indicate that LFZS09 regulates antibiotic-induced motor impairment in mice, thereby offering a theoretical foundation for future studies and probiotic or parabiotics production aimed at augmenting motor function.
研究领域:
微生物学
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神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
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2022
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IF 3.889
Zhongmei He,He Yu,Hong Wu,Lili Su,Kun Shi,Yan Zhao,Ying Zong,Weijia Chen,Rui Du
Context Fibraurea recisa Pierre. (Menispermaceae) (FR) is a traditional Chinese medicine known as “Huangteng.” The total alkaloids of FR (AFR) are the main active ingredients. However, the pharmacological effects of AFR in the treatment of depression have not been reported.Objectives This study investigates the antidepressant effects of AFR by network pharmacology and verification experiments.Materials and methods Compound-Target-Pathway (C-P-T) network of FR and depression was constructed through network pharmacology. In vitro, HT-22 cells were treated with corticosterone (CORT) solution (0.35 mg/mL), then AFR (0.05 mg/mL) solution and inhibitor AZD6244 (14 μM/mL) or BAY11-7082 (10 μM/mL) were added, respectively. The cell viability was detected by CCK-8. In vivo, C57BL/6 mice were divided into 5 groups, namely the normal group, the CUMS group, the AFR (400 mg/kg) group, and the 2 groups that were simultaneously administered the inhibitory group AZD6244 (8 mg/kg) and BAY11-7082 (5 mg/kg). Western blotting was used to assess the expression level of the proteins.Results AFR could protect HT-22 cells from CORT-induced damage and increase the cell viability from 49.12 ± 3.4% to 87.26 ± 1.5%. Moreover, AFR significantly increased the levels of BDNF (1.3, 1.4-fold), p-ERK (1.4, 1.2-fold) and p-CERB (1.6, 1.3-fold), and decreased the levels of NLRP3 (11.3%, 31.6%), ASC (19.2%, 34.2%) and caspase-1 (18.0%, 27.6%) in HT-22 cells and the hippocampus, respectively.Discussion and conclusions AFR can improve depressive-like behaviours and can develop drugs for depression treatment. Further studies are needed to validate its potential in clinical medicine.
研究领域:
药理学
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神经科学
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中医药
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DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2017
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IF 5.012
Jun Tang,Hongping Miao,Bing Jiang,Qianwei Chen,Liang Tan,Yihao Tao,Jianbo Zhang,Fabao Gao,Hua Feng,Gang Zhu,Zhi Chen
Microglia play dual roles after germinal matrix hemorrhage, and the neurotrophic phenotype maybe neuroprotective . However, the phenotype transformation and the way by which neuron-microglia dialogue remain unclear. We raise the hypothesis that a cannabinoid receptor2 agonist (JWH133) accelerates the CX3CR1 + microglia secreting neurotrophic factors and restores damaged neuronal circuit. Here, we report a novel function of JWH133 in transforming the microglia CX3CR1 positive that secrete brain-derived neurotrophic factor (BDNF), which triggers neuron proliferation and neuronal restoration. Using a collagen VII-induced GMH model in rat pups postnatal day 7 (P7), we found that the drug showed robust activity in neuronal precursors. Moreover, the FA value of DTI in the internal zone revealed the positive effects of JWH133 on neural restoration. CX3CR1, a critical modulating molecule expressed in microglia, was upregulated after treatment with JWH133 and the corresponding shRNA (NM_133534.1) was used to silence the expression of CX3CR1. 3 days after treatment with JWH133, we detected reduced expression of biomarkers for neural progenitor cells (NPCs) in pups pre-injected in the lateral ventricular tissue with CX3CR1 shRNA, but not in pups injected with control shRNA. Overall, this study provides evidence that JWH133 promoted a neurotrophic phenotype of microglia (CX3CR1 + microglia), beyond merely alleviating microglial proliferation and inflammation. Moreover, JWH133 restored impaired neuronal circuit, which represent a novel therapeutic strategy following GMH in clinic.
研究领域:
神经科学
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药理学
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神经生物学
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产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2022
·Vol. 17
·期 1
·1-20
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IF 4.546
Yu Hui,Shao Shumin,Xu Junnan,Guo Haibiao,Zhong Zhangfeng,Xu Jiangping
Background Fresh or dried Persimmon leaves (Diospyros kaki Thunb.) exhibit preventive effects on cardiovascular and cerebrovascular diseases. However, their antidepressant effects and underlying mechanisms are unclear. Thus, we investigated mechanisms responsible for Persimmon leaf extract (PLE) activity on chronic social defeat stress (CSDS)-induced depressive-like behaviors in mice.Methods CSDS was used as a mouse model of depression. We performed the sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) to identify depressive-like behavior. Spine density and dendritic morphology were assessed using Golgi staining. Neurochemicals were quantified by microdialysis, doublecortin by immunofluorescence, and cAMP using an ELISA kit. Finally, the levels of cortical proteins of phosphorylated cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), postsynaptic density synapsin-1 and protein 95 (PSD95) were quantified by western blot. 16S rRNA gene sequencing was used to detect fecal microbiota.Results Treatment of CSDS-subjected mice with PLE (30.0–60.0 mg/kg, i.g.) enhanced sucrose preference, decreased immobility times in the TST and FST but did not affect locomotor activity. Furthermore, persistent social defeat stress decreased dendritic spine density and dendritic length in the brain, as well as decreased PSD95 and synapsin-1 expression. PLE, interestingly, inhibited dendritic spine loss and increased synaptic protein levels. PLE also increased brain levels of 5-HT, cAMP, phosphorylated (p)-CREB, BDNF, PSD95, and synapsin-1 in mice subjected to CSDS. Furthermore, PLE increased their doublecortin-positive cell count in the hippocampal dentate gyrus. CSDS mice represented a distinct fecal microbiota cluster which differed compared with normal C57BL/6J mice, and the phenotype was rescued by PLE.Conclusion sPLE alleviated CSDS-induced depressive behaviors and spinal damage by suppressing serotonin reuptake and activating the cAMP/CREB/BDNF signaling pathway. Simultaneously, PLE influenced the composition of the fecal microbiota in CSDS-subjected mice.
研究领域:
药理学
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神经科学
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行为科学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Zhangjie Wu,Ying Yin,Ruiyi Liu,Xianhui Li,Yan Sun,Suk-yu Yau,Lei Wu,Yan Liu,Miroslav Adzic,Hailou Zhang,Gang Chen
Ethnopharmacological relevance Jiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet Aim of the study Here we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula Materials and methods Individual herbs (MC ; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba ) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested using a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) is used as a positive control for induction of rapid antidepressant effects Results A combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment, in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA Conclusion GMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity
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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行为科学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
·
IF 8
Xinyu Fan,Jiachen Shi,Ye Liu,Mengqiu Zhang,Min Lu,Ding Qu
Background Berberine (BR) shows promise as a candidate for treating irritable bowel syndrome with diarrhea (IBS-D). However, the undesired physicochemical properties and poor oral absorption limit its clinical translation. A ketogenic diet (KD) can induce intestinal overexpression of cannabidiol (CB) receptors, which may offer a potential target for IBS-D-specific delivery of BR.Methods The microemulsions loaded with BR and decorated with cannabidiol (CBD/BR-MEs) were developed through a one-step emulsion method. The pharmaceutical behaviors of the CBD/BR-MEs were measured using dynamic light scattering and high-performance liquid chromatography. The efficacy of the anti-IBS-D therapy was evaluated by assessing fecal water content, Bristol score, and AWR score. The intestinal permeability were assessed through immunofluorescent staining of CB1 and ZO-1, respectively. The signaling of CREB/BDNF/c-Fos was also studied along with immunofluorescent and immunohistochemical examination of brain sections.Results The CBD/BR-MEs, which had a particle size of approximately 30 nm and a surface density of 2% (wt%) CBD, achieved greater than 80% (wt%) encapsulation efficiency of BR. The pharmacokinetics performance of CBD/BR-MEs was significantly improved in the KD-fed IBS-D rats than the standard diet-fed ones, which is highly related to intestinal expression of CB1 receptors. The treatment with CBD/BR-MEs and KD exhibited evident comprehensive advantages over the other groups in terms of anti-IBS-D efficacy. CBD/BR-MEs and KD synergistically decreased intestinal permeability. Moreover, the treatment with CBD/BR-MEs and KD not only blocked the CREB/BDNF/c-Fos signaling in the brain but also decreased the levels of neurotrophic factors, neurotransmitters, and inflammatory cytokines in the serum of IBS-D model rats.Conclusion Such a design represents the first attempt at IBS-D-targeted drug delivery for improved oral absorption and efficacy through KD-induced target exposure, which holds promising potential for the treatment of IBS-D.
研究领域:
药学
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胃肠病学
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营养科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neuroscience Bulletin
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2022
·Vol. 38
·期 11
·1347-1364
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IF 5.271
Yu Jie,Cheng Yao,Cui Yaru,Zhai Yujie,Zhang Wenshen,Zhang Mengdi,Xin Wenyu,Liang Jia,Pan Xiaohong,Wang Qiaoyun,Sun Hongliu
An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
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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癫痫研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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