Biophilic Positive Carbon Dot Exerts Antifungal Activity and Augments Corneal Permeation for Fungal Keratitis.

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.

Looking for a Beam of Light to Heal Chronic Pain.

Chronic pain (CP) is a leading cause of disability and a potential factor that affects biological processes, family relationships, and self-esteem of patients. However, the need for treatment of CP is presently unmet. Current methods of pain management involve the use of drugs, but there are different degrees of concerning side effects. At present, the potential mechanisms underlying CP are not completely clear. As research progresses and novel therapeutic approaches are developed, the shortcomings of current pain treatment methods may be overcome. In this review, we discuss the retinal photoreceptors and brain regions associated with photoanalgesia, as well as the targets involved in photoanalgesia, shedding light on its potential underlying mechanisms. Our aim is to provide a foundation to understand the mechanisms underlying CP and develop light as a novel analgesic treatment has its biological regulation principle for CP. This approach may provide an opportunity to drive the field towards future translational, clinical studies and support pain drug development.

Eukaryotes may play an important ecological role in the gut microbiome of Graves' disease.

The prevalence of autoimmune diseases worldwide has risen rapidly over the past few decades. Increasing evidence has linked gut dysbiosis to the onset of various autoimmune diseases. Thanks to the significant advancements in high-throughput sequencing technology, the number of gut microbiome studies has increased. However, they have primarily focused on bacteria, so our understanding of the role and significance of eukaryotic microbes in the human gut microbial ecosystem remains quite limited. Here, we selected Graves' disease (GD) as an autoimmune disease model and investigated the gut multi-kingdom (bacteria, fungi, and protists) microbial communities from the health control, diseased, and medication-treated recovered patients. The results showed that physiological changes in GD increased homogenizing dispersal processes for bacterial community assembly and increased homogeneous selection processes for eukaryotic community assembly. The recovered patients vs. healthy controls had similar bacterial and protistan, but not fungal, community assembly processes. Additionally, eukaryotes (fungi and protists) may play a more significant role in gut ecosystem functions than bacteria. Overall, this study gives brief insights into the potential contributions of eukaryotes to gut and immune homeostasis in humans and their potential influence in relation to therapeutic interventions.

The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model.

Background: Curcumin is a natural compound with extensive pharmacological effects. This research is to verify the optimal dose and administration duration efficacy of curcumin in alleviating the movement symptoms of Parkinson's disease (PD). Methods: Wistar rats were divided into six groups including control, model, levodopa treatment and low/middle/high (40/80/160 mg/kg/d) curcumin treatment groups. After stereotactic brain injection of 6-hydroxydopamine (6-OHDA), curcumin was given by intragastric administration for 2 weeks. To evaluate the drug effect, the rats received behavioral tests including apomorphine (APO)-induced rotation test, rotarod test and open field test. Then the rats were sacrificed and the brain slices including substantia nigra pars compacta (SNc) were used for immunofluorescence staining. Results: After 6-OHDA injection, the model group showed typical movement symptoms including the severe APO-induced rotation to the healthy side, decreased latency in the rotarod with constant or accelerative mode, and decreased total distance and average speed in the open field test. In the results of immunofluorescence staining, the 6-OHDA induced a severe damage of dopaminergic neurons in SNc. The 160 mg/kg/d treatment of curcumin to intervene for 2 weeks alleviated most of the behavioral disorders but the 40/80 mg/kg/d treatment showed limitations. Then, we compared the effect of 1 week intervention to the 2 weeks with 160 mg/kg/d treatment of curcumin to intervene and results indicated that the treatment of 2 weeks could better alleviate the symptoms. Conclusions: Curcumin alleviated 6-OHDA-induced movement symptoms in a PD rat model. Additionally, the effect of curcumin against PD indicated dose and duration dependent and the intervention of 160 mg/kg/d for 2 weeks showed optimally therapeutic effect.

Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development.

Premenstrual dysphoric disorder (PMDD) can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones. Its core symptoms (emotional instability, irritability, depression, and anxiety) are related to the increase of stress sensitivity due to the fluctuation of hormone level in luteal phase of the menstrual cycle. In this review, we describe the emotional regulatory effect of allopregnanolone (ALLO), and summarize the relationship between ALLO and γ-aminobutyric acid A (GABAA) receptor subunits based on rodent experiments and clinical observations. A rapid decrease in ALLO reduces the sensitivity of GABAA receptor, and reduces the chloride influx, hindered the inhibitory effect of GABAergic neurons on pyramidal neurons, and then increased the excitability of pyramidal neurons, resulting in PMDD-like behavior. Finally, we discuss in depth the treatment of PMDD with targeted GABAA receptors, hoping to find a precise target for drug development and subsequent clinical application. In conclusion, PMDD pathophysiology is rooted in GABAA receptor sensitivity changes caused by rapid changes in ALLO levels. Targeting GABAA receptors may alleviate the occurrence of PMDD.

A chitosan-based self-healing hydrogel for accelerating infected wound healing.

Wound infection causes irregular tissue closure, often with prolonged healing. Traditional therapies based on antibiotic delivery have resulted in reduced therapeutic efficiency and drug resistance. Such features make it highly desirable to develop an antibiotic-free material for wound infection in clinical applications. Herein, a self-healing antibacterial hydrogel was designed to realize the treatment of S. aureus-infected wounds. The design of the dynamic imine bond endows hydrogels with self-healing and adaptive properties, which could cover the irregular wound and improve the safety of administration. In addition, benefiting from quaternized chitosan, the designed hydrogels also present fascinating antimicrobial properties and favorable biocompatibility. The evaluation in a rat skin wound infection model indicates that the fascinating antimicrobial effect accelerates wound healing by the designed hydrogels. This facile design of an antibiotic-free material allows effective wound infection management, which may be promising in coping with other complex wound healings.

Deep brain stimulation on the external segment of the globus pallidus improves the electrical activity of internal segment of globus pallidus in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the progressive degeneration of neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) is an effective treatment for PD cardinal motor symptoms. DBS of GPe has been recognized as an effective treatment option for motor symptoms of PD, but the mechanism is still essentially unknown. To investigate the impact of DBS in the external segment of globus pallidus (GPe) on the pathway of the basal ganglia (BG), we recorded the electrical activities of single neurons and local field potential (LFP) of the internal segment of globus pallidus (GPi). The results showed that the firing rate of GPi neurons in the 6-OHDA lesioned rats returned to the normal level after GPe-DBS for two weeks. Moreover, the CV value of GPi neurons is significantly lower than that in the PD group. The different frequency bands of GPi LFP in PD rats have improved correspondingly. These findings indicate that the improvement of the electrical activity of GPi by GPe-DBS in PD rats may be an important electrophysiological mechanism for treating PD.

The efficacy of therapies for post-stroke depression in aging: An umbrella review.

Post-stroke depression (PSD) is a common complication after stroke. PSD is associated with emotional disorders and psychological dependence, which are potential risk factors for stroke recurrence and suicidality. This study aimed to perform an umbrella review of therapies for PSD through a comprehensive literature search. A systematic search was conducted in the PubMed and Web of Science by two independent authors. We examined the Hamilton Depression Scale (HAMD), Activities of daily living (ADL), Neurologic function as efficacy endpoints, and the incidence of adverse events as safety profiles. Seventeen eligible studies, including 267 clinical trials were included in this study. The results showed that High-Frequency Repetitive Transcranial Magnetic Stimulation (HfrTMS), Acupuncture/EA+conventional treatment, Escitalopram, Modified Sini San, Moxibustion, Xiaoyao Formula, Paroxetine, Chinese herbal medicine, Exercise, Citalopram, and Cognitive behavioral therapy are beneficial for improving the depression symptoms of patients with PSD. HfrTMS and Sertraline may have an impact on slowing the scores of activities of daily living or neurologic function. In addition, Acupuncture/EA+conventional, Escitalopram, Citalopram, Sertraline, and Fluoxetine showed no serious adverse events in PSD patients. Our study demonstrated that 11 treatment methods can effectively improve the condition of PSD patients.

Oxytocin and serotonin in the modulation of neural function: Neurobiological underpinnings of autism-related behavior.

Autism spectrum disorders (ASD) is a group of generalized neurodevelopmental disorders. Its main clinical features are social communication disorder and repetitive stereotyped behavioral interest. The abnormal structure and function of brain network is the basis of social dysfunction and stereotyped performance in patients with autism spectrum disorder. The number of patients diagnosed with ASD has increased year by year, but there is a lack of effective intervention and treatment. Oxytocin has been revealed to effectively improve social cognitive function and significantly improve the social information processing ability, empathy ability and social communication ability of ASD patients. The change of serotonin level also been reported affecting the development of brain and causes ASD-like behavioral abnormalities, such as anxiety, depression like behavior, stereotyped behavior. Present review will focus on the research progress of serotonin and oxytocin in the pathogenesis, brain circuit changes and treatment of autism. Revealing the regulatory effect and neural mechanism of serotonin and oxytocin on patients with ASD is not only conducive to a deeper comprehension of the pathogenesis of ASD, but also has vital clinical significance.

A novel curcumin oil solution can better alleviate the motor activity defects and neuropathological damage of a Parkinson's disease mouse model.

Curcumin has been reported to improve or prevent movement disorders in Parkinson's disease (PD); however, its low bioavailability is the biggest obstacle to its application. To optimize the limited efficacy of curcumin and to improve its protective effects against PD, we prepared and tested a novel curcumin oil solution. In vivo imaging was used to confirm that the curcumin oil solution has higher bioavailability than curcumin alone. To test its motor effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced movement disorders, behavioral tests, including the open-field test, pole test, rotarod test, and automated gait analysis were used. Finally, pathological evaluation using immunohistochemistry and western blotting analysis was done. Encouragingly, the behavioral test findings exhibited a better protective effect against MPTP-induced movement disorders. In addition, it had a greater protective effect on dopaminergic neurons in the compact part of the substantia nigra along with the PD process according to pathological evaluation. This novel curcumin oil solution may provide a new choice for PD prevention as a dietary supplement or clinically assisted treatment based on its better bioavailability and efficiency.

Beta band modulation by dopamine D2 receptors in the primary motor cortex and pedunculopontine nucleus in a rat model of Parkinson's disease.

Beta band (12-30 Hz) hypersynchrony within the basal ganglia-thalamocortical network has been suggested as a hallmark of Parkinson's disease (PD) pathophysiology. Abnormal beta band oscillations are found in the pedunculopontine nucleus (PPN) and primary motor cortex (M1) and are correlated with dopamine depletion. Dopamine acts locomotion and motor performance mainly through dopamine receptors (D1 and D2). However, the precise mechanism by which dopamine receptors regulate beta band electrophysiological activities between the PPN and M1 is still unknown. Here, we recorded the neuronal activity of the PPN and M1 simultaneously by the administration of the drug (SCH23390 and raclopride), selectively blocking the dopamine D1 receptor and D2 receptor. We discovered that the increased coherent activity of the beta band (12-30 Hz) between M1 and PPN in the lesioned group could be reduced and restored by injecting raclopride in the resting and wheel running states. Our studies revealed the unique role of D2 dopamine receptor signaling in regulating ß band oscillatory activity in M1 and PPN and their relationship after the loss of dopamine, which contributes to elucidating the underlying mechanism of the pathophysiology of PD.

Jie-Yu-He-Huan Capsule Ameliorates Anxiety-Like Behaviours in Rats Exposed to Chronic Restraint Stress via the cAMP/PKA/CREB/BDNF Signalling Pathway.

Chronic stress is a critical factor in the aetiology of anxiety disorders; however, in the clinic, enduring and preventive measures are not available, and therapeutic drugs are associated with inevitable side effects. Our study established an anxiety rat model using chronic restraint stress (CRS) and assessed these animals using the open-field test, elevated plus-maze test, and light-dark box test. Jie-Yu-He-Huan capsule (JYHH), a Chinese medicine formula, was used as a preventative drug. The HPA axis-mediated release of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone from the hypothalamus was tested. In the hippocampus and prefrontal cortex, concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid, as well as monoamine oxidase A, glucocorticoid receptor, and 5-HT1A receptor expression levels, were measured. Furthermore, we examined protein and mRNA expression of cAMP-PKA-CREB-BDNF pathway components. The results showed that JYHH had a significant preventative effect on the anxiety-like behaviour induced by CRS and prevented abnormal changes in the HPA axis and 5-HT system. Furthermore, CRS inhibited the cAMP-PKA-CREB-BDNF pathway, which returned to normal levels following JYHH treatment. This might be the underlying molecular mechanism of the antianxiety effect of JYHH, which could provide a new clinical target for preventative anxiolytic drugs for chronic stress.

Levodopa affects spike and local field synchronisation in the pedunculopontine nucleus of a rat model of Parkinson's disease.

The pedunculopontine nucleus (PPN) undergoes significant anatomic and electrophysiological alterations in Parkinson's disease (PD), severely impacting locomotion. However, the effect of 6-hydroxydopamine (6-OHDA) lesion and levodopa (L-DOPA) therapy on the relationships between spike activities and local field potential (LFP) within the PPN is not well-understood. Synchronisation between the spike activity of individual neurones and LFP of neuronal ensembles is a crucial problem in the pathogenesis of PD. In this study, LFP signals and spikes in the PPN of rats in control, lesioned, and L-DOPA groups were recorded synchronously with a multi-unit electrical signal acquisition system and analysed for their coherence value, spike-field coherence, and phase-lock relationship. The spike-LFP relationship in the PPN was markedly increased in specific frequency bands because of the 6-OHDA lesion but differed depending on the animal locomotion state and neuronal type. L-DOPA had a limited therapeutic effect on the 6-OHDA-induced increase in the coherence value. Our study demonstrates that the PPN spike-LFP relationship is involved in the pathogenesis of PD and is critical for the effects of L-DOPA, providing a basis for the clinical treatment of refractory PD symptoms.

Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis.

Gemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665 (LINC00665) were found to rank the top 10 upregulated lncRNAs in our study, and high LINC00665 expression was closely associated with poor prognosis and chemoresistance of CCA patients. Silencing LINC00665 in gemcitabine resistant CCA cells impaired gemcitabine tolerance, while enforced LINC00665 expression increased gemcitabine resistance of sensitive CCA cells. The gemcitabine resistant CCA cells showed increased EMT and stemness properties, and silencing LINC00665 suppressed sphere formation, migration, invasion and expression of EMT and stemness markers. In addition, Wnt/ß-Catenin signaling was activated in gemcitabine resistant CCA cells, but LINC00665 knockdown suppressed Wnt/ß-Catenin activation. B-cell CLL/lymphoma 9-like (BCL9L), the nucleus transcriptional regulators of Wnt/ß-Catenin signaling, plays a key role in the nucleus translocation of ß-Catenin and promotes ß-Catenin-dependent transcription. In our study, we found that LINC00665 regulated BCL9L expression by acting as a molecular sponge for miR-424-5p. Moreover, silencing BCL9L or miR-424-5p overexpression suppressed gemcitabine resistance, EMT, stemness and Wnt/ß-Catenin activation in resistant CCA cells. In conclusion, our results disclosed the important role of LINC00665 in gemcitabine resistance of CCA cells, and provided a new biomarker or therapeutic target for CCA treament.

Inhalation Administration of Agarwood Incense Rescues Scopolamine-Induced Learning and Memory Impairment in Mice.

Background: Agarwood, a type of herbal medicine widely used in Asian countries, is noted in traditional medicine for its intelligence-enhancing effects. Agarwood incense is traditionally administered by oral and nasal inhalation. To verify whether agarwood incense can exert its intelligence-enhancing effects in this way to rescue learning and memory impairment, typical clinical manifestations of dementia, we conducted a set of behavioral tests related to learning and memory. Methods: C57BL/6 mice were divided into six groups. In addition to the control and model groups, we added a donepezil treatment group to evaluate the effect of three different agarwood administration doses. After a week of administration, scopolamine was injected 30 min before each behavioral test to create a learning and memory impairment model. A series of behavioral tests [the Morris water maze test (MWM), the novel object recognition test (NOR), and the step-down test (SDT)] were used to assess their learning ability, as well as their spatial and recognition memory. Results: After scopolamine injection, the model group showed significant learning and memory impairment (i.e., longer latencies, lower crossing times, and lesser distance travelled in the target quadrant in MWM; a lower recognition index in NOR; and longer latencies and higher error times in SDT). The other four treatment groups all showed improvements in these indicators, and the overall therapeutic effect of agarwood was superior. Conclusion: The inhalation administration of agarwood can significantly improve the learning and memory impairment caused by scopolamine in mice, and the therapeutic effect varied between doses.

A forced swim-based rat model of premenstrual depression: effects of hormonal changes and drug intervention.

Premenstrual dysphoric disorder (PMDD), a form of premenstrual syndrome (PMS), is a severe health disturbance that affects a patient's emotions; it is caused by periodic psychological symptoms, and its pathogenesis remains unclear. As depression-like symptoms are found in a majority of clinical cases, a reliable animal model of premenstrual depression is indispensable to understand the pathogenesis. Herein, we describe a novel rat model of premenstrual depression, based on the forced swimming test, with a regular estrous cycle. The results showed that in the estrous cycle, the depression-like behavior of rats occurred in the non-receptive phase and disappeared in the receptive phase. Following ovariectomy, the depression-like symptoms disappeared and returned after a hormone priming regimen. Moreover, fluoxetine, an anti-depressant, could reverse the behavioral symptoms in these model rats with normal estrous cycle. Further, the model rats showed significant changes in the serum levels of estrogen and progesterone, hippocampal levels of allopregnanolone, 5-hydroxytryptamine, norepinephrine, and γ-aminobutyric acid (GABA), and in the expression of GABAA receptor 4α subunit, all of which were reversed to physiological levels by fluoxetine. Overall, we established a reliable and standardized rat model of premenstrual depression, which may facilitate the elucidation of PMS/PMDD pathogenesis and development of related therapies.

LncRNA HOTAIR suppresses cell apoptosis, autophagy and induces cell proliferation in cholangiocarcinoma by modulating the miR-204-5p/HMGB1 axis.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor in the world. LncRNA HOX transcript antisense intergenic RNA (HOTAIR) was identified as a crucial regulator in various cancers including CCA. This study aimed to unravel the functions of HOTAIR and its biological mechanism in CCA, hinting for the new therapeutic targets in CCA. METHODS: The levels of HOTAIR, miR-204-5p and HMGB1 in CCA tissues and cell lines (HuB28 and HuCCT1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was conducted to detect the protein levels of LC3-I, LC3-II, Beclin-1 and HMGB1. The relationships among HOTAIR, miR-204-5p and HMGB1 were examined by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay. Cell proliferation ability and apoptosis rate were assessed by CCK8 assay and flow cytometry, respectively. in vivo experiment was conducted to examine the bio-functions of HOTAIR in nude mice. RESULTS: HOTAIR and HMGB1 were over-expressed, while miR-204-5p was lowly expressed in CCA tissues and cells. The dual-luciferase reporter assay indicated that miR-204-5p was a target of HOTAIR, and HMGB1 was a target of miR-204-5p. The restoration experiments showed that HOTAIR repressed cell apoptosis, autophagy and promoted cell proliferation via miR-204-5p/HMGB1 axis. Additionally, HOTAIR silencing retarded the xenograft tumor growth by up-regulation of miR-204-5p and down-regulation of HMGB1. CONCLUSION: These data unraveled that lncRNA HOTAIR regulated HMGB1 to suppress cell apoptosis, autophagy and induce cell proliferation by sponging miR-204-5p in CCA. Thus, this new regulatory pathway may provide new therapeutic targets for CCA.

Glycogen synthase kinase-3ß promotes radiation-induced lung fibrosis by regulating ß-catenin/lin28 signaling network to determine type II alveolar stem cell transdifferentiation state.

The role of type II alveolar epithelial stem cells (AEC II) for alveolar repair in radiation-induced lung fibrosis (RILF) remains largely unknown, mainly because of AEC II phenotype's spontaneous change in vitro. Cell differentiation status is determined by Lin28 and let-7 miRNAs in see-saw-pattern. Lin28, a repressor of let-7 and a stem cell marker, is activated by ß-catenin. The expression of ß-catenin is regulated by GSK-3ß/TGF-ß1 signaling. To understand the true role of AEC II in RILF, we freshly isolated primary AEC II directly from thoracically irradiated lungs. We then explored the expressions of cell phenotype markers and differentiation regulators in these isolated AEC II to analyze the correlation between GSK-3ß/TGF-ß1/ß-catenin signaling pathway, lin28/let-7 balance, and AEC II phenotypes at different injury phases following irradiation. Results showed that isolated single primary cells displayed AEC II ultrastructural features and proSP-C positive. The gene expressions of prosp-c (an AEC II biomarker) and hopx (an AEC I marker) significantly increased in isolated AEC II during injury repair phase (P < .001 and P < .05) but decreased at end-stage of injury, while mesenchymal markers increased in both isolated AEC II and irradiated lungs. mRNA levels of gsk-3ß, tgf-ß1, and ß-catenin increased in all irradiated AEC II, but more pronounced in the second half of injury phase (P < .05-P < .001). Similarly, the expression of lin28 was also significantly elevated in isolated AEC II at the late phase (P < .05-P < .001). Four let-7 miRNAs were significantly upregulated in all irradiated AEC II groups (P < .05-P < .001). The time-dependent and highly consistent uptrends for four lin28/let-7 ratios in sorted AEC II contrasted to downtrends in irradiated lungs. In conclusion, RILF occurred when GSK-3ß/TGF-ß1 signaling increased ß-catenin levels, which led to the augmentation of AEC II population by elevated lin28/let-7 ratio and the transcription of profibrotic cytokines and factors, thereby inducing AEC II to undergo transdifferentiation into mesenchymal cells.

Paeonol at Certain Doses Alleviates Aggressive and Anxiety-Like Behaviours in Two Premenstrual Dysphoric Disorder Rat Models.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS), a common mental health disturbance associated with several periodic psychological symptoms in women. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMS/PMDD patients; however, side effects are inevitable, especially in long-term treatment. In previous studies, the natural compound paeonol in Moutan Cortex was found to play effective roles in central nervous system disorders with its anti-inflammatory, anti-oxidant, and neuroprotective effects. Consequently, we assume that paeonol might produce positive effects in the treatment of PMS/PMDD. In this study, the open-field test (OFT) and elevated plus maze (EPM) and light dark box (LDB) tests were performed in mice to determine the optimal dose of paeonol for treating anxiety. Then, paeonol was used to treat the progesterone withdrawal (PWD) and resident intruder paradigm (RIP) rat models of PMDD. Using these two reliable models, the OFT and EPM, LDB, and composite aggressive tests were performed to evaluate the effect of the drug on behavioural symptoms of PMDD. From the dosage screening results, the optimal anti-anxiety dose of paeonol was identified as 17.5 mg/kg/d for 7 days. With regard to the effect of paeonol on PMDD rat models, a significantly improvement was found in the behavioural symptoms, but the effective dose varied in different models. For the PWD model rats, treatment with 6.05 mg/kg paeonol could significantly improve anxiety and irritability, while that with 24.23 mg/kg paeonol resulted in anxiety-like effects in behavioural tests. In RIP model rats, treatment with 12.11 mg/kg paeonol demonstrated excellent effects in improving anxiety, particularly irritable emotional behaviour. In conclusion, our study indicates that paeonol is a potential therapeutic compound for PMS/PMDD; it is a drug option that helps establish dosage guidance for treatment of this condition.