Xi-Yu Zhao, Zhen-Qi Wu, Tian-Yu Zhang+4 more · 2026 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
Attention deficit hyperactivity disorder(ADHD), a common neurodevelopmental disorder in children, is characterized by inattention, hyperactivity, and impulsivity. Epidemiological surveys show that the Show more
Attention deficit hyperactivity disorder(ADHD), a common neurodevelopmental disorder in children, is characterized by inattention, hyperactivity, and impulsivity. Epidemiological surveys show that the prevalence of ADHD in children is gradually increasing worldwide, and it is the most common childhood mental disorder in China. Because of the complex clinical symptoms, multiple co-morbidities, and unknown etiology, ADHD has far-reaching negative impacts on individuals, families, and the society. Behavioral interventions, as a pillar in the management of ADHD, play a targeted role in improving children's social functioning, with significant benefits supported by evidence. However, they are constrained by uneven resources, poor compliance, and insufficient continuity, Western medicine has multiple adverse effects and unclear long-term effects in the treatment of ADHD despite the definite efficacy. Accordingly, there is an urgent need to find safe and effective therapies suitable for children. With a holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has significant advantages in treating ADHD via multiple targets, which involves dopamine(DA), norepinephrine(NE), 5-hydroxytryptamine(5-HT), cyclic adenosine monophosphate(cAMP), brain-derived neurotrophic factor(BDNF) and other signaling pathways. Through these pathways, TCM can treat ADHD through the regulation of neurotransmitters, enhancement of prefrontal and striatal functions, enhancement of neuronal protection, attenuation of neuroinflammation, and reduction of neuronal apoptosis. However, a systematic study remains to be conducted. This paper summarizes the signaling pathways related to the treatment of ADHD by TCM in the past two decades, aiming to provide reference for delving into the mechanism and exploring effective TCM prescriptions for ADHD in children and to give full play to the advantages of the efficacy and characteristics of TCM. Show less
The brain-derived neurotrophic factor ( A total of 43 first-episode mania patients (FEM), 110 multiple-episode mania patients (MEM) and 80 healthy controls were enrolled in our study. We investigated Show more
The brain-derived neurotrophic factor ( A total of 43 first-episode mania patients (FEM), 110 multiple-episode mania patients (MEM) and 80 healthy controls were enrolled in our study. We investigated the impact of We found a significant interaction between This is the first study to demonstrate that The online version contains supplementary material available at 10.1186/s12888-026-07949-7. Show less
Press needle therapy, may alleviate depressive-like behaviors. Male rats were randomly allocated into four groups ( Press-needle ameliorated depressive-like behaviors in CUMS-exposed rats, restored bo Show more
Press needle therapy, may alleviate depressive-like behaviors. Male rats were randomly allocated into four groups ( Press-needle ameliorated depressive-like behaviors in CUMS-exposed rats, restored body weight gain and improved behavioral performance. The treatment upregulated the hippocampal BDNF/TrkB/CREB signaling pathway, increasing BDNF, TrkB, CREB, AKT, and PI3K in the hippocampus. The therapy modulated serotonergic neurotransmission by increasing hippocampal 5-HTT expression, while downregulating 5-HT1A and 5-HT2C receptors and PKA. Notably, press-needle exerted anti-neuroinflammatory effects, reducing hippocampal and serum levels of TNF-α and IL-6. Histopathological analysis confirmed its neuroprotective efficacy, demonstrating attenuated neuronal damage in hippocampal tissues. Show less
This study investigated the expression of brain-derived neurotrophic factor (BDNF) signaling components (BDNF-TrkB-AKT1) and apoptosis-related factors (Bcl-2 and Bax) in yak brain regions at different Show more
This study investigated the expression of brain-derived neurotrophic factor (BDNF) signaling components (BDNF-TrkB-AKT1) and apoptosis-related factors (Bcl-2 and Bax) in yak brain regions at different altitudes. The cerebral cortex, cerebellum, hippocampus, thalamus, and medulla oblongata were collected from 3-year-old yaks living at low and high altitudes. The relative mRNA expression of BDNF, TrkB, AKT1, Bcl-2, and Bax was assessed by qRT-PCR. Protein abundance and cellular localization of BDNF, TrkB, AKT1, Bcl-2, and Bax were evaluated by Western blotting and immunohistochemistry, with immunoreactivity quantified by optical density analysis. Within each altitude group, BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and the corresponding protein levels (BDNF, TrkB, AKT1, and Bcl-2) were significantly higher in the cerebral cortex and hippocampus than in the cerebellum, thalamus, and medulla oblongata (P < 0.05). In contrast, Bax mRNA and Bax protein levels did not differ significantly among the five regions. Compared with low-altitude yaks, high-altitude yaks showed significantly higher BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and higher BDNF, TrkB, AKT1, and Bcl-2 protein levels in brain tissues (P < 0.05), whereas Bax protein expression did not differ between altitude groups. Immunohistochemistry revealed immunoreactivity for BDNF, TrkB, AKT1, Bcl-2, and Bax in both altitude groups, with prominent labeling in cortical pyramidal neurons and across the pyramidal cell layer in the hippocampal CA region. Immunoreactivity was also detected in large neurons of the thalamus and medulla oblongata. In the cerebellum, labeling was strongest in Purkinje cells, with weaker signals in the granule cell layer and molecular layer. BDNF-TrkB-AKT1 pathway components and Bcl-2 showed relatively higher expression in the cerebral cortex and hippocampus within each altitude group, whereas Bax expression did not vary across regions. These patterns are consistent with an association between BDNF-TrkB-AKT1 signaling and increased Bcl-2 expression without a corresponding increase in Bax, which may support neuronal adaptation in the cerebral cortex and hippocampus. Elevated expression of BDNF, TrkB, AKT1, and Bcl-2 at high altitude suggests enhanced adaptation to hypoxia in high-altitude yaks; the underlying mechanisms require further investigation. Show less
Acute spinal cord injury (SCI) results in irreversible neurological deficits. We hypothesized that local transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with erythropoietin (EPO Show more
Acute spinal cord injury (SCI) results in irreversible neurological deficits. We hypothesized that local transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with erythropoietin (EPO) would inhibit glial scarring and accelerate functional recovery. To quantify the therapeutic efficacy and underlying mechanisms of BMSCs+EPO versus BMSCs alone in a rat model of acute SCI. Forty SD rats (T10 Allen 60 g·cm impact) were randomized to sham, SCI, SCI+BMSCs, or SCI+BMSCs+EPO ( At 4 weeks, BBB scores in the BMSCs+EPO group reached 12.7 ± 1.5, representing a 54% increase over the BMSCs-alone group (8.3 ± 0.7, BMSCs+EPO exerts synergistic neuroprotective effects, achieving superior locomotor recovery compared with BMSCs monotherapy, and represents a promising adjuvant strategy for acute SCI. Show less
Chaihu Shugan San (CSS), a classical Traditional Chinese Medicine (TCM) formula, was first recorded in Jingyue Quanshu (1624 AD) for treating "liver qi stagnation" (Yu Syndrome), a TCM diagnostic patt Show more
Chaihu Shugan San (CSS), a classical Traditional Chinese Medicine (TCM) formula, was first recorded in Jingyue Quanshu (1624 AD) for treating "liver qi stagnation" (Yu Syndrome), a TCM diagnostic pattern analogous to modern mood disorders. Although CSS has been prescribed for emotional distress, irritability, and depressive symptoms for centuries, the neurobiological mechanisms underlying its antidepressant efficacy, particularly in the context of gender-specific pathology, remain poorly revealed. The present study probed the antidepressant effects of CSS in female mice, while elucidating the underlying molecular mechanisms involving hippocampal neuroinflammation and neuroplasticity. We hypothesized that CSS reverses chronic stress-induced depressive phenotypes by suppressing interleukin-6 (IL-6), which in turn facilitates cAMP-CaMKII-BDNF signaling pathway in the hippocampus. Adult female C57BL/6J mice were subjected to a 5-week chronic unpredictable mild stress (CUMS) regimen to evoke depressive-like behaviors. During the final 2 weeks of the regimen, CSS was administered intragastrically at 0.5, 1.0, or 1.5 g/kg, with fluoxetine (10 mg/kg) as the positive control. Behavioral assessments included forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and tail suspension test (TST). Hippocampal IL-6, cAMP, CaMKII, and BDNF levels were quantified by ELISA. Mechanistic validation employed acute hippocampal microinjection of recombinant IL-6 (1 μg/site) and systemic administration of the CaMKII inhibitor KN-93 (6 mg/kg). Chemical constituents were identified by UHPLC-QTOF MS. CSS alleviated CUMS-induced depressive-like behaviors in a dose-dependent manner, cutting down immobility time in TST/FST and reinstating sucrose preference, similar to the action of fluoxetine. CSS significantly suppressed hippocampal IL-6 while upregulating cAMP, CaMKII activity, and BDNF expression. Acute IL-6 elevation completely abolished both the behavioral antidepressant effects and molecular actions of CSS. Pharmacological inhibition of CaMKII blocked CSS-induced behavioral improvement and its upregulation of cAMP-BDNF signaling, without affecting basal behaviors. CSS exhibited no anxiogenic or locomotor side effects. CSS exerts potent antidepressant effects in female mice through coordinated suppression of hippocampal IL-6 and activation of the cAMP-CaMKII-BDNF neuroplasticity-related pathway, with CaMKII playing a critical role in this process. These findings offer scientific evidence for the traditional use of CSS in addressing emotional disorders and highlight its therapeutic potential as a multi-targeted, anti-inflammatory botanical medicine for female-specific depression. Show less
Neuroplasticity is the core process by which the brain responds to aging, learning, and injury. Reporting positive non-pharmacological intervention approaches to promote neural plasticity is a core fo Show more
Neuroplasticity is the core process by which the brain responds to aging, learning, and injury. Reporting positive non-pharmacological intervention approaches to promote neural plasticity is a core focus of contemporary neuroscience and rehabilitation medicine. Tai Chi (TC), as a traditional Chinese physical and mental practice that deeply combines soothing body movements, breathing regulation, and spiritual focus, is increasingly attracting attention from the scientific community for its role in facilitating brain health. Our review seeks to combine recent evidence, elucidate how TC promotes neural plasticity via multi-level mechanisms, discuss its advantages in promoting cognitive, motor, and emotional functions, and investigate its clinical utilization prospects and future research challenges in neurorehabilitation. According to reviewing recent literature, we combined evidence from cross-sectional studies, randomized controlled trials, systematic reviews, and meta-analyses, with a center on citing research findings utilizing multimodal neuroimaging techniques (such as fMRI, fNIRS, EEG) and molecular biology techniques to construct a complete chain of evidence from molecules to systems. TC drives multi-level neural plasticity modifications via its unique physical and mental combination properties. At the macro level, it can enhance the gray matter volume of the hippocampus and prefrontal cortex, and promote the organizational effectiveness of large-scale functional networks in the brain. At the micro molecular level, TC establishes a favorable microenvironment for neuronal survival, synaptic plasticity, and neural repair by upregulating BDNF, increasing endogenous antioxidant defense, modulating inflammatory balance, and improving mitochondrial energy metabolism. These structural, functional, and molecular level changes collectively form the neurobiological basis for TC to promote memory and executive function, increase balance and motor management, and promote emotional regulation ability. Our review further assesses the clinical effectiveness of TC in the rehabilitation of neurological diseases, such as Parkinson's disease (PD), stroke, and mild cognitive impairment, determining that it not only decreases symptoms, but may also have the possible role to decrease disease development. Ultimately, our review delve into the challenges and future perspectives experienced by this range in the context of standardization of research paradigms, causal reasoning of mechanisms, and individualized interventions. Show less
Microglial decline in the dentate gyrus is an important mechanism in the development of depression-like behaviors in stressed animals. Reversing this decline with low-dose lipopolysaccharide (LPS) can Show more
Microglial decline in the dentate gyrus is an important mechanism in the development of depression-like behaviors in stressed animals. Reversing this decline with low-dose lipopolysaccharide (LPS) can produce rapid antidepressant effects, yet the underlying mechanisms remain incompletely understood. Our previous work identified a critical role for astrocytic P2Y1 receptor (P2Y1R) activation and subsequent dentate gyrus extracellular signal-regulated kinase 1/2 (ERK1/2)-brain-derived neurotrophic factor (BDNF) signaling in the antidepressant effect of low-dose LPS. This study elucidates the signaling cascade linking astrocytic P2Y1R mobilization to the antidepressant effect of low-dose LPS. We found that low-dose LPS promoted glutamate release through ATP-triggered astrocytic P2Y1R signaling. Blockade of N-methyl-D-aspartic acid (NMDA) receptors, but not metabotropic receptors, and the GluN2B subtype of NMDA receptors abolished the antidepressant effect of low-dose LPS. GluN2B knockdown also abolished the reversal effect of low-dose LPS on CUS-induced depression-like behaviors and impairment of dentate gyrus ERK1/2-BDNF signaling. Moreover, chelating intracellular Ca Show less
Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. T Show more
Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. This study aimed to observe the mechanism of EA as an adjunct therapy to escitalopram oxalate (EO) on depressed patients. This study was designed as a single-blinded, double-dummy randomized controlled trial. 61 participants were diagnosed with mild-to-moderate depression according to the International Classification of Diseases 10th Edition (ICD-10, F32) were randomly allocated to receive EA + EO placebo, EO + sham EA, or EA + EO for six weeks treatment. The clinical assessment including depression severity, quality of life (QOL) and clinical safety. Biological indicators of immune-inflammation, the brain-derived neurotrophic factor and glucocorticoid inducible genes in peripheral blood of participants were measured by using enzyme linked immunosorbent assay and real-time polymerase chain reaction respectively before and after treatment. Three interventions improved the depression severity and QOL (P < 0.05), and no inter-group difference was found in the 6th week (P > 0.05). Anxiety psychic and somatic general symptoms in the EA + EO group were improved significantly than those of the other two groups (P < 0.05). After six-week treatment of EA + EO, blood SGK1 mRNA, GILZ mRNA, and BDNF levels were increased significantly ( Show less
Acetylation, a key post-translational modification, is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Among HDACs, HDAC6-a class II deacetylase with predo Show more
Acetylation, a key post-translational modification, is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Among HDACs, HDAC6-a class II deacetylase with predominant cytoplasmic localization-plays a unique role in cellular processes that extend beyond histone modification. It is ubiquitously expressed throughout the central and peripheral nervous systems and is integral to key physiological functions including protein quality control, autophagy, mitochondrial transport, and oxidative stress responses. Notably, under pathological conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, and peripheral nerve injury, HDAC6 undergoes nuclear translocation and contributes to epigenetic dysregulation by modulating the transcription of genes such as brain-derived neurotrophic factor, thereby impairing synaptic integrity and function. This dual role-cytoplasmic in protein homeostasis and nuclear in transcriptional regulation-highlights the HDAC6 paradox in neurological disorders. This review summarizes recent understanding of HDAC6's structure, expression, and functions within the nervous system, and discuss how targeting HDAC6 with selective inhibitors offers a promising therapeutic strategy for mitigating neurological disease pathogenesis. The goal is to provide insights that bridge HDAC6's roles in protein quality control and epigenetic regulation, fostering further exploration of HDAC6 inhibition in neurologic therapeutics. Show less
Depression and anxiety disorders are highly comorbid, yet their complex pathogenesis often limits the efficacy of monotherapy. Growing evidence implicates neuroinflammation in their pathogenesis. Co-d Show more
Depression and anxiety disorders are highly comorbid, yet their complex pathogenesis often limits the efficacy of monotherapy. Growing evidence implicates neuroinflammation in their pathogenesis. Co-drugs that linked two active molecules into a single compound and released the drugs after administration, which offering improved efficacy and tolerability than individual drug mixtures or monotherapy. In this work, five new co-drugs ODV-NSAIDs were synthesized from O-desmethylvenlafaxine (ODV) with non-steroidal anti-inflammatory drugs (NSAIDs) to achieve synergistic antidepression and anxiolytic effects. In vitro stability studies exhibited that these co-drugs can be metabolized into two single drugs within 60 min in simulated intestinal fluid. In both acute and chronic LPS-induced models, co-drug ODV-NAP significantly ameliorated depressive-like behaviors, evidenced by increased sucrose preference, reduced immobility in the tail suspension test (TST) and forced swim test (FST), and enhanced locomotion in the open field test (OFT). Furthermore, ODV-NAP decreased brain levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and malondialdehyde (MDA), while elevating serotonin (5-HT), norepinephrine (NE), and superoxide dismutase (SOD) activity. Nissl staining confirmed ODV-NAP significantly attenuated hippocampal neuronal damage. Moreover, western blotting revealed ODV-NAP inhibited the TLR4/NF-κB signaling pathway and upregulated BDNF and p-TrkB protein expression. ODV-NAP also inhibited LPS-induced p65 nuclear translocation in BV-2 microglia in vitro, and caused no toxicity in histology. Thus, co-drug ODV-NAP represented a promising novel candidate for treating depression and anxiety. Show less
The Angelica sinensis and Ligusticum chuanxiong Herb Pair (DC) serves as a core pairing in Traditional Chinese Medicine for treating blood stasis and blood deficiency syndromes, which are frequently a Show more
The Angelica sinensis and Ligusticum chuanxiong Herb Pair (DC) serves as a core pairing in Traditional Chinese Medicine for treating blood stasis and blood deficiency syndromes, which are frequently associated with depressive-like symptoms in clinical practice. The antidepressant potential of this combination aligns with its traditional functions of promoting qi circulation, activating blood flow, and alleviating depression. This study aims to investigate the antidepressant effects of DC and its potential mechanisms through a combination of network pharmacology prediction and in vitro and in vivo experimental validation. Network pharmacology screening identified active components and target molecules in DC, constructing a component-target network and validating binding activity through molecular docking. A CUMS-induced rat model of depression was established, with drug efficacy evaluated via behavioral tests (forced swim, sucrose preference, and open field tests) and blood rheology parameters measured. ELISA assay of neurotransmitter and inflammatory factor levels in serum and hippocampal tissue, Observation of histopathological changes in hippocampal tissue using HE and Nissl staining, Western blot and immunofluorescence assays were performed to detect the expression of proteins in the PI3K/AKT pathway. An in vitro inflammatory model was established by inducing BV-2 cells with LPS. The MTT assay was used to screen for the safe concentration of drug-containing serum and observe cell morphology, the Gries method for detecting NO release, ELISA for detecting inflammatory cytokines, Western blot analysis of PI3K/AKT pathway proteins was performed, and pathway inhibition was validated using LY294002. Through network pharmacology analysis, seven major active components of DC and 197 related functional targets for depression treatment were identified, with the majority enriched in the PI3K/AKT signaling pathway. Behavioral studies and in vivo experiments indicate that DC significantly ameliorates depressive-like behaviors in CUMS rats, reduces blood viscosity, increases hippocampal tissue levels of 5-HT, NE, and DA, decreases IL-1β, IL-6, and TNF-α content, and mitigates hippocampal neuronal damage. Western blot and immunofluorescence results indicate that DC can activate the PI3K/AKT pathway, upregulating p-AKT and BDNF expression. In vitro experiments further confirmed that the drug-containing serum could suppress LPS-induced inflammatory responses in BV-2 cells, reducing the release of factors such as NO and IL-1β. This effect was reversible upon treatment with the PI3K inhibitor LY294002. DC exhibits potent antidepressant effects by modulating the PI3K/AKT pathway to enhance neurotransmitter release and reduce inflammatory factor levels. This mechanism protects neurons and alleviates neuroinflammation, thereby exerting antidepressant effects. Show less
Anxiety and depression are growing global burdens with limited drug options. Traditional Chinese medicine (TCM) offers unique advantages, including Roudoukou-Suanzaoren (RS), an ancient TCM-derived be Show more
Anxiety and depression are growing global burdens with limited drug options. Traditional Chinese medicine (TCM) offers unique advantages, including Roudoukou-Suanzaoren (RS), an ancient TCM-derived beverage with the potential for treating these conditions. This study aims to explore whether this combination improves the outcomes. The results show that the main constituents of RS include flavonoids, terpenoids, alkaloids, and phenylpropanoids. Behavioral and histopathological analyses demonstrate that RS alleviates chronic restraint stress (CRS)-induced anxiety- and depression-like behaviors and attenuates neuropathological damage in relevant brain regions; the underlying mechanism is likely mediated by the CREB/BDNF/TrkB signaling pathway. Meanwhile, RS reduces proinflammatory cytokines in tissues, decreases hippocampal microglial numbers, and increases astrocytes. Additionally, RS attenuates colonic injury, restores intestinal permeability, upregulates tight-junction proteins, and improves gut microbiota dysbiosis. This study highlights that RS exerts antianxiety and antidepression effects by modulating the gut microbiota, controlling inflammatory responses, and increasing BDNF levels through the "gut-brain axis" pathway. Show less
Classic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), have emerged as potent modulators of neuroplasticity and metaplasticity in the adult brain Show more
Classic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), have emerged as potent modulators of neuroplasticity and metaplasticity in the adult brain, offering novel therapeutic strategies for neuropsychiatric disorders. Recent findings reveal that beyond their transient psychotropic effects, these compounds activate serotonin 5-HT Show less
Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to Show more
Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to explore the therapeutic potential of RTG against CRS-induced depression-like behaviors and cognitive deficits in mice and to uncover the associated molecular mechanisms. A depression-like and cognitive impairment model was established in C57BL/6 male mice using chronic restraint stress (CRS). Six-week-old C57BL/6 male mice were randomly assigned to the following groups: control (Con), model (CRS), RTG (10 mg/kg), XE-991 (2 mg/kg) or tunicamycin (Tm, 2 mg/kg). Behavioral tests were conducted to assess depression-like behaviors and cognitive function. Hippocampal neuronal morphology was examined by H&E and immunofluorescence staining, while changes in endoplasmic reticulum stress (ERS)-related signaling pathways were analyzed by Western blot. Retigabine treatment reduced hippocampal neuronal damage and the expression of ERS-related factors (GRP78, CHOP) and the pro-apoptotic factor BAX in CRS-induced mice, while it increased the levels of BDNF. These effects were antagonized by XE-991 and the ERS agonist tunicamycin (Tm). Retigabine may alleviate CRS-induced depressive-like behaviors and cognitive impairment by inhibiting ERS-mediated apoptosis, suggesting its potential as a novel therapeutic strategy for depression. Show less
In vitro maturation (IVM) is highly susceptible to influences of the culture environment, which can lead to increased intracellular reactive oxygen species (ROS) levels and thereby induce a stress res Show more
In vitro maturation (IVM) is highly susceptible to influences of the culture environment, which can lead to increased intracellular reactive oxygen species (ROS) levels and thereby induce a stress response in oocytes, ultimately reducing the developmental potential of early embryos. Brain-derived neurotrophic factor (BDNF) is an ovarian endocrine factor that can enhance the function of follicular granulosa cells and promote oocyte maturation, but the specific pathways remain unclear. We supplemented IVM cultures of sheep oocytes with BDNF and examined aspects of oocyte nuclear and cytoplasmic maturation. The addition of 50 ng/mL BDNF promoted the expansion of cumulus cells and increased the rates of first polar body extrusion, cleavage, and blastocyst formation. Compared with untreated controls, BDNF-treated oocytes had improved Ca Show less
A series of novel naphthoquinone[2,3-d] thiazole derivatives were designed as 17β-HSD10 inhibitors. Compound 14 emerged as the lead candidate, demonstrating potent 17β-HSD10 inhibition (IC
(1) Background: The increasing environmental concentration of polystyrene nanoplastics (PS-NPs) may pose a risk of human exposure and health threats. Previous studies have demonstrated that exposure t Show more
(1) Background: The increasing environmental concentration of polystyrene nanoplastics (PS-NPs) may pose a risk of human exposure and health threats. Previous studies have demonstrated that exposure to PS-NPs poses a threat to neural synaptic plasticity, yet the underlying mechanisms remain unclear. (2) Methods: Hippocampal astrocytes and neurons were co-cultured, exposed to PS-NPs at concentrations of 10, 50, and 100 μg/mL, and cytotoxicity was assessed. We investigated PS-NP-induced impairment of synaptic plasticity by regulating the brain-derived neurotrophic factor (BDNF). (3) Results: Calmodulin-dependent protein kinase II (CaMKII) is a central molecular organizer of synaptic plasticity, learning, and memory, and its activity is intrinsically linked to intracellular calcium ion concentration. Our research indicates that PS-NPs may interfere with calcium ion signaling and CaMKIIα activity, thereby reducing CaMKIIα activity. This subsequently downregulates the expression of cAMP response element-binding protein (CREB), modulates BDNF expression, and impacts synaptic plasticity. (4) Conclusions: In summary, this study primarily focused on the effects of PS-NPs exposure on hippocampal synaptic plasticity. Show less
Arterial thrombectomy (AT) is a cornerstone in the treatment of acute ischemic stroke (AIS) due to large vessel occlusion. However, the optimal therapeutic time window and the best management strategy Show more
Arterial thrombectomy (AT) is a cornerstone in the treatment of acute ischemic stroke (AIS) due to large vessel occlusion. However, the optimal therapeutic time window and the best management strategy for patients presenting beyond the conventional 4.5-hour timeframe remain areas of active investigation and debate. This retrospective cohort study aimed to analyze the effect of timing of AT on recovery in AIS. We retrospectively analyzed 117 AIS patients admitted between January 2021 and January 2023. Participants were categorized into 3 groups: early AT (onset-to-AT < 4.5 hours), late AT (onset-to-AT ≥ 4.5 hours), and late AT + intravenous thrombolysis (IT). Outcomes compared included clinical efficacy, National Institutes of Health Stroke Scale (NIHSS) scores, serum levels of neurotrophic factors, brain-derived neurotrophic factor, vascular endothelial growth factor, residual stenosis, vessel reocclusion, 3-month mortality, and 1-month complications. The total effective rate was higher in the early AT and late AT + IT groups than in the late AT group. Pretreatment NIHSS scores and serum neurological marker levels were comparable across all groups. After treatment, the early AT and late AT + IT groups showed significantly lower NIHSS scores, higher serum levels of neurological markers, and improved treatment efficiency compared to the late AT group. Prognosis-related markers also indicated better outcomes in these 2 groups. Additionally, complications such as mucocutaneous ecchymosis, gastrointestinal bleeding, and intracranial bleeding were significantly reduced in the early AT and late AT + IT groups. AT within 4.5 hours of stroke onset improves efficacy, reduces neurological injury, and decreases complications. For patients presenting beyond 4.5 hours, combining AT with IT achieves comparable therapeutic benefits. Show less
Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study dem Show more
Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exert profound therapeutic effects in a rat model of moderate-to-severe CP established via bilateral carotid artery occlusion with hypoxia. Intravenously administered hUCMSC-Exos displayed sustained brain retention and significantly restored motor coordination and cognitive function. The recovery was primarily mediated through enhanced remyelination driven by promoted oligodendrocyte maturation and differentiation (elevated oligodendrocyte lineage transcription factor 2 and myelin basic protein). Concurrently, the treatment attenuated key pathological processes involving sustained neuroinflammatory responses (reduced ionized calcium-binding adapter molecule 1, tumor necrosis factor-α, and interleukin-6) while elevating brain-derived neurotrophic factor. Our findings establish hUCMSC-Exos as a promising dual-modality therapy for moderate-to-severe CP, mechanistically linked to robust remyelination and coordinated modulation of core disease mechanisms. Show less
This study aimed to investigate changes in brain structure and function of hippocampus in aged type 2 diabetes mellitus (T2DM) rats and the effects of tea polyphenol (TP) intervention using magnetic r Show more
This study aimed to investigate changes in brain structure and function of hippocampus in aged type 2 diabetes mellitus (T2DM) rats and the effects of tea polyphenol (TP) intervention using magnetic resonance imaging (MRI) and tissue-level molecular analyses. Rats were randomly assigned to six groups: Control, Aged, Aged T2DM, Aged T2DM + TP, Aged T2DM + rosiglitazone, and Aged T2DM + piracetam intervention groups. Anxiety- and depression-like behaviors were assessed using the open field test, the forced swimming test and elevated plus maze. Brain structure, blood flow and neuro-associated metabolites were evaluated via MRI. The number of nerve cells, neurons, microglia and astrocytes, the expression of BDNF/CREB/p-CREB protein, the levels of inflammatory factors, and the integrity of the myelin sheath in the hippocampus were evaluated. Relationships between behavioral, cellular and molecular changes and MRI-derived indicators were evaluated by Pearson correlation analysis. Aged T2DM rats exhibited severe anxiety- and depression-like behaviors accompanied by brain atrophy, reduced blood flow and decreased brain metabolites. At the microstructural level, the number of hippocampal neurons in the Aged T2DM group was significantly reduced, accompanied by increased counts of microglia and astrocytes. Meanwhile, the expression levels of hippocampal p-CREB and BDNF were decreased, the concentration of the inflammatory factor IL-1β, IL-6, TNF-α was elevated, and myelin integrity was impaired. Intervention with TP alleviated anxiety- and depression-like behavior, with MRI-detected abnormalities and in vitro histopathological molecular changes improved (except for myelin integrity). TP intervention mitigated alterations in brain structure and function as well as anxiety and depression-like behaviors in aged T2DM rats. Show less
Ischemic stroke is a leading cause of mortality and disability worldwide, and there is an urgent need for safe dietary agents with neuroprotective potential. Water-soluble tomato concentrate (WSTC), a Show more
Ischemic stroke is a leading cause of mortality and disability worldwide, and there is an urgent need for safe dietary agents with neuroprotective potential. Water-soluble tomato concentrate (WSTC), a tomato-derived functional ingredient approved in Europe for cardiovascular health, was evaluated for its protective effects against cerebral ischemia-reperfusion injury. Using a middle cerebral artery occlusion/reperfusion rat model and oxygen-glucose deprivation/reoxygenation neuronal model, we demonstrated that WSTC improved cerebral perfusion, reduced infarct volume, alleviated histopathological damage, and enhanced neurological recovery. Mechanistic studies integrating transcriptomics, network pharmacology, and molecular assays revealed that WSTC inhibited oxidative stress and neuronal apoptosis while activating the ERK/CREB/BDNF signaling pathway. These findings provide the first comprehensive evidence that WSTC confers multi-target neuroprotection and highlight its translational potential as a safe, plant-based functional food ingredient for promoting brain health and reducing ischemic injury. Show less
Chronic pain (CP) and major depressive disorder (MDD) are highly disabling global diseases, and their high comorbidity creates a bidirectional vicious cycle, significantly exacerbating functional impa Show more
Chronic pain (CP) and major depressive disorder (MDD) are highly disabling global diseases, and their high comorbidity creates a bidirectional vicious cycle, significantly exacerbating functional impairment and treatment resistance. Multidisciplinary evidence suggests that the comorbid nature arises from deep functional coupling and neural network remodeling between the sensory-pain and emotional systems, rather than merely a symptom overlap. Neuroimaging, animal models, and neuromodulation studies demonstrate that key brain regions, including the prefrontal cortex (PFC), anterior cingulate cortex (ACC), amygdala, hippocampus, insula, and reward system, show consistent abnormalities in the comorbid state, creating a cross-brain network that jointly regulates pain, emotion, and cognition. This paper systematically reviews the central structures, neural circuits, and neurotransmitter regulatory mechanisms of CP-MDD comorbidity and proposes an integrated emotion-perception coupling network model. We highlight the mechanisms and translational potential of multi-pathway intervention strategies, with a focus on neuromodulation techniques (rTMS, tDCS), combined with ketamine, BDNF modulators, and anti-inflammatory drugs. Additionally, it is emphasized that future research must integrate multimodal imaging, multi-omics data, and computational modeling to establish a mechanism-driven personalized stratification system. With the support of high spatiotemporal resolution brain connectomics technology, this will facilitate the transition from a 'symptom control' to a 'mechanism repair' paradigm in treating comorbidities. Show less
Alzheimer's disease (AD) is a common dementia in the elderly population, typically manifested through symptoms of cognitive impairment (CI) and memory loss. Pathologically, it is characterized by abno Show more
Alzheimer's disease (AD) is a common dementia in the elderly population, typically manifested through symptoms of cognitive impairment (CI) and memory loss. Pathologically, it is characterized by abnormally elevated levels of amyloid-β (Aβ) deposition and tau phosphorylation. Given the rapid rate of population aging, many scientists are investigating AD, focusing on its pathogenic mechanisms and potential treatments. Unfortunately, to date, no highly effective therapeutic strategies have emerged. Intriguingly, multiple studies have revealed alterations in the gut microbiome of individuals with AD, suggesting it may serve as a novel avenue for investigating AD pathogenesis. Show less
4-Methylethcathinone (4-MEC), a synthetic cathinone with psychostimulant properties, is increasingly abused as a "designer drug". However, its molecular mechanisms, particularly those related to neuro Show more
4-Methylethcathinone (4-MEC), a synthetic cathinone with psychostimulant properties, is increasingly abused as a "designer drug". However, its molecular mechanisms, particularly those related to neuroplasticity regulation, remain poorly understood. Caveolin-1 (CAV1) is a scaffolding protein of membrane lipid rafts and has been confirmed to organize multiple synaptic signaling proteins to regulate synaptic signaling and neuroplasticity. Herein, we investigated whether CAV1 modulates 4-MEC-induced alterations in the BDNF-TrkB signal pathway and neuroplasticity markers in human SH-SY5Y neuroblastoma cells and a mouse-conditioned place preference (CPP) model. Using qRT-PCR and Western blotting, we demonstrated that 4-MEC significantly upregulated CAV1 mRNA and protein levels, as well as components of the BDNF-TrkB signaling pathway and neuroplasticity markers (GAP43, MAP2, SYP). siRNA-mediated CAV1 knockdown abolished 4-MEC-induced increases in these proteins and neuroplasticity-related mRNAs, whereas CAV1 overexpression potentiated these effects. Additionally, molecular docking predicted potential binding sites between 4-MEC and CAV1. Meanwhile, protein docking also predicted the potential binding sites between CAV1 and TrkB, and co-immunoprecipitation confirmed their physical interactions in SH-SY5Y cells. In the mice exposed to 4-MEC in the CPP paradigm, we observed similar upregulation of CAV1, BDNF-TrkB signaling pathway components, and neuroplasticity markers in the brain. These findings identify CAV1 as a potential critical mediator of 4-MEC's neuroadaptive effects through the BDNF-TrkB signal pathway to regulate neuroplasticity. It suggests a possible novel molecular target for synthetic cathinone toxicity, with potential implications for forensic research. Show less
Oxidative stress-induced enteric neuropathy is a key driver of slow-transit constipation (STC), primarily through disrupted mitochondrial dynamics and neuronal degeneration. To address this, we develo Show more
Oxidative stress-induced enteric neuropathy is a key driver of slow-transit constipation (STC), primarily through disrupted mitochondrial dynamics and neuronal degeneration. To address this, we developed a bioengineered oral delivery system that supports neuronal recovery and actively enhances mitochondrial membrane fusion. A self-assembling amphiphilic peptide (GFF) was synthesized to encapsulate rhein (RH), a natural anthraquinone with antioxidant, anti-inflammatory, and microbiota-regulating properties. A BDNF-derived tetrapeptide was integrated to further potentiate neurotrophic effects. These components were co-assembled into a therapeutic nanofiber (RFI), which was embedded in a chitosan/sodium alginate hydrogel for sustained oral delivery. In vitro and in vivo studies demonstrated that RFI significantly improved neuronal viability and gastrointestinal motility. Mechanistic investigations revealed that RFI is associated with activation of the AKT signaling pathway and enhancement of mitochondrial membrane fusion, collectively contributing to the restoration of mitochondrial network integrity and neuronal protection. This multifunctional nanoplatform offers a promising therapeutic approach to STC by combining targeted delivery with direct modulation of mitochondrial function. Show less
Formononetin (FMN) is known for its significant neuroprotective effects, this study aims to investigate the antidepressant potential and underlying mechanisms of FMN. Antidepressant efficacy was evalu Show more
Formononetin (FMN) is known for its significant neuroprotective effects, this study aims to investigate the antidepressant potential and underlying mechanisms of FMN. Antidepressant efficacy was evaluated in corticosterone (CORT)-induced depression models. In vivo, CORT-exposed mice received FMN to assess behavioral and hippocampal changes (dendritic spine density, synaptic markers: MAP-2/GAP-43). In silico, network pharmacology and molecular docking predicted FMN's binding affinity and enriched pathways. In vitro, HT22 cells pretreated with FMN (10 μM, 6 h) were subjected to CORT injury, with mechanistic validation via ERα antagonist (MPP) and ERK inhibitor (PD98059). FMN alleviated depressive-like behaviors and preserved hippocampal integrity in mice. Bioinformatics analysis revealed FMN's strong binding to ER subtypes and enrichment in estrogen/MAPK pathways. In vitro, FMN pretreatment activated the ERK-CREB-BDNF axis in CORT-injured HT22 cells, enhancing neuronal survival and synaptic function. The activation was ERα/ERK-dependent, as evidenced by the abolition of protective effects following pharmacological inhibition with MPP (ERα antagonist) or PD98059 (ERK inhibitor). Concomitantly, in vivo FMN treatment restored hippocampal p-ERK/ERK ratios in mice, directly corroborating the ERK-CREB-BDNF pathway activation and highlighting its efficacy in reversing CORT-induced signaling deficits. FMN exerts antidepressant effects via ERα-mediated neurotrophic signaling (ERK-CREB-BDNF), offering a mechanistic foundation for natural antidepressant development. Show less
The neurotrophic factor (NTF) family has recently expanded its role beyond neurological conditions, but its involvement in acute inflammatory lung diseases remains largely unclear. Using well-establis Show more
The neurotrophic factor (NTF) family has recently expanded its role beyond neurological conditions, but its involvement in acute inflammatory lung diseases remains largely unclear. Using well-established acute lung injury (ALI) and sepsis models, we demonstrate that brain-derived neurotrophic factor (BDNF), a key NTF, is impaired in pulmonary epithelial cells and negatively correlates with the inflammatory response. Raising the BDNF level alleviates inflammatory lung injury, but these effects are absent in macrophage-deleted mice. Both in vivo and in vitro results show BDNF inhibits macrophage inflammation, and further proteomics analysis identifies macrophage TLR4 as a receptor that BDNF antagonizes via direct binding. The BDNF fragment (aa 104-115) is critical for BDNF-TLR4 interaction, and the corresponding synthetic BDNF-derived dodecapeptide (BDP-12) retains TLR4-antagonistic and anti-inflammatory effects both in vitro and in vivo, without pro-proliferative side effects. In conclusion, our findings reveal that epithelial-derived BDNF prevents macrophage inflammation by directly targeting TLR4 and highlights BDP-12 as a potential therapeutic agent for acute inflammatory diseases. Show less
Shanglai Li, Bingru Zhao, Yu Cai+5 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
The pituitary gland plays a pivotal role in regulating puberty and reproductive physiology; however, the precise cellular and molecular mechanisms driving the pubertal transition in large animal, such Show more
The pituitary gland plays a pivotal role in regulating puberty and reproductive physiology; however, the precise cellular and molecular mechanisms driving the pubertal transition in large animal, such as ewes, remain poorly understood. Here, we generated a comprehensive single-cell transcriptomic atlas of the ovine anterior pituitary, specifically comparing the pre-pubertal (3 month) and post-pubertal (6 month) stages. We identified 30 335 cells classified into ten distinct clusters. Comparative analysis revealed a global transcriptional reprogramming during puberty, characterized by a marked upregulation of genes associated with ribosome biogenesis, unfolded protein response, and hormone secretion across endocrine cells, reflecting an expanded biosynthetic capacity. Specifically, we identified SCG2 as a critical regulator of gonadotroph maturation. Functional validation demonstrated that SCG2 facilitates the biogenesis of secretory granules, thereby promoting FSH synthesis and secretion. Furthermore, intercellular communication analysis uncovered a distinct shift in the pituitary microenvironment: the 6 month pituitary exhibited enhanced regulatory networks, including IGF signaling mediated by non-endocrine cells and NT signaling (e.g., BDNF-NTRK2) driven by multiple cell types. These findings suggest that the onset of puberty relies on a coordinated "endocrine-to-endocrine" and "non-endocrine-to-endocrine" crosstalk. This study provides a high-resolution molecular blueprint of the pubertal transition, highlighting the key roles of biosynthetic machinery upgrades and microenvironmental remodeling in establishing the high reproductive performance of Hu sheep. Show less