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Research Progress on Pathogenesis and Therapeutic Drugs of Alzheimer’s Disease LIU Chang, MENG Xian-yong, DONG Xiao-hua ACTA NEUROPHARMACOLOGICA 2020, 10 (4): 36-40. DOI:10.3969/j.issn.2095-1396.2020.04.007 Abstract（ 287） PDF（1085KB）（ 79） Alzheimer’s disease（AD） is a progressive neurodegenerative disease with concealed onset and development. The main morbidity group is the elderly. The clinical manifestations of AD are mainly the dysfunction of body functions such as behavior，memory and expression. AD can be easily ignored in the early stage，so as to miss the best treatment period.It has seriously affected the life and health of the elderly.With the aggravation of social aging，prevention and treatment of AD has become an important topic in global research.The current research shows that the pathogenesis of AD include abnormal precipitation of Aβ protein hyperphosphorylation of Tau protein and abnormalities of cholinergic system. In recent years，researchers all over the world have developed many drugs for treating AD through continuous exploration and research. Although the number of therapeutic drugs is increasing，the condition of AD is very complicated，and its pathogenesis cannot be determined. Most drugs are only used to relieve symptoms，and there are no drugs for truly complete treatment. This article reviews the pathogenesis of AD and the progress in drug therapy in recent years. Reference|Related Articles|Metrics

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Relationship between Adult Hippocampus Neurogenesis and Alzheimer’s Disease DING Sheng-kai, LIU Qing-qing, LIU Xin-yang, SHANG Ya-zhen ACTA NEUROPHARMACOLOGICA 2020, 10 (6): 48-53. DOI:10.3969/j.issn.2095-1396.2020.06.009 Abstract（ 270） PDF（1082KB）（ 59） Alzheimer’s disease(AD)is a common neurodegenerative disease in old age and has been published by world health organization(WHO)as one of the largest global public health issues facing mankind. The main clinical symptom is the progressive decline of learning and memory ability. The neuropathological changes of AD include senile plaque(SP)formed byβ-amyloid protein(Aβ)of accumulated outside of neuon，neurofibrillary tangle(NFT)formed by hyperphosphorylated Tau protein of inside the neuron，neuron loss and degeneration，synapse decrease and so on. Especially，the abnormal neurogenesis is also involved in the neuropathological process of AD. There are many studies have showed that neurogenesis is a process of neural stem cells in hippocampal dentate gyrus of adult mammals to produce new neuron. The increased adult neurogenesis can compensate the injured neurons and save the learning and memory impairment. Then，the promotion of adult hippocampal neurogenesis may be beneficial to treatment of AD. The present paper summarizes the relationship between the adult hippocampal neurogenesis and Alzheimer’s disease. Related Articles|Metrics

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Research Progress on the Role of Oxidative Stress in Diabetic Nephropathy and Its Antioxidant Treatment HAO Jun-rong, NIU Hong-shuang, LIU Yi-zhou, DONG Xiao-hua ACTA NEUROPHARMACOLOGICA 2020, 10 (2): 33-38. DOI:10.3969/j.issn.2095-1396.2020.02.007 Abstract（ 234） PDF（1103KB）（ 51） Diabetic kidney disease is one of the most common and major complications in diabetic patients. It occurrences rate is higher and has extremely high rates of morbidity and mortality worldwide. Oxidation should play a significant role in the course of diabetic kidney disease. Diabetes can enhance the activity of the oxidation of emergency. Oxidative stress is one of the pathogenesis of diabetic kidney disease which can lead to diabetes complications. Oxidative stress can also lead to renal interstitial，glomerular and renal cell damage，and damage of kidney function. Due to oxidative stress is associated with inflammatory cells with dense，it often exists at the same time，they activate each other. ROS can be mediated kidney inflammation and accelerate the development of diabetic kidney disease，high sugar also affect kidney function by influencing the renal blood flow. Based on the close relationship between oxidative stress and diabetic kidney disease，antioxidants should be considered to treat diabetic nephropathy. At present，Vc，Ve and ACEI drugs can be used for diabetic nephropathy clinically，as well as some other antioxidants such as calcium antagonists，PKC inhibitors and even Traditional Chinese medicine. In the future，oxidative stress can be targeted to study more and better drugs for the treatment of diabetic kidney disease. Related Articles|Metrics

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The Relationship Between Astrocytes and Ischemic Stroke GUO Zixia, ZHANG Danshen ACTA NEUROPHARMACOLOGICA 2021, 11 (1): 18-23. DOI:10.3969/j.issn.2095-1396.2021.01.003 Abstract（ 109） PDF（921KB）（ 47） Stroke is a central nervous system disease with a very high incidence nowadays，which seriously endangers human health. As the most widely distributed cell in the brain，astrocytes play an important role in the nervous system and are closely related to stroke. This article describes the relationship between astrocytes and stroke through the physiological role of astrocytes，hoping to provide more references for the basic research and treatment of stroke in the future. Related Articles|Metrics

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Research Progress of Signal Pathways in Drug Treatment of Ulcerative Colitis GUO Zi-xia, AN Zi-xuan, ZHANG Jian-mei, ZHANG Dan-shen ACTA NEUROPHARMACOLOGICA 2020, 10 (4): 41-50. DOI:10.3969/j.issn.2095-1396.2020.04.008 Abstract（ 145） PDF（1223KB）（ 43） Ulcerative colitis （UC） is a disease affected by multiple factors and is prone to repeated attacks. It is one of the most intractable diseases recognized in the world. The effect of current drug treatment is not good，so people pay more and more attention to it. This article mainly reviews the signal pathways related to UC pathogenesis and the effects of therapeutic drugs，to provide more reference for future research on new drugs or new mechanisms，and to classify and evaluate the modeling methods of animal models used in experiments，in order to provide references for researchers to choose suitable models. Reference|Related Articles|Metrics

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Roles of Histone Acetylation in Aging HUANG Bo-yue, YANG Bao-xue ACTA NEUROPHARMACOLOGICA 2021, 11 (2): 53-64. DOI:10.3969/j.issn.2095-1396.2021.02.010 Abstract（ 182） PDF（1480KB）（ 38） As a complex multi-factor biological process，aging is characterized by the gradual decline of cell homeostasis，tissue function and body health over time. Aging weakens the gene expression control regulated by epigenetic factors. Histone modification is a key regulatory factor that controls chromatin structure and gene transcription，thereby affecting various important cellular biological processes. More and more studies have shown that histone acetylation under various environmental stimuli is involved in the regulation of translation，which affects gene expression and lifespan. In this review，we summarize the mechanisms of histone acetylation in gene regulation and senescence，describe the direct or indirect roles of histone acetylation in the aging-related gene expression and signaling pathways，and discuss the potential of histone acetylation as therapeutic targets against aging. Related Articles|Metrics

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Betulinic Acid Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury by Inhibiting the Phosphorylation of P38 Mitogen-Activated Protein Kinases in Rats#br# #br# ZHANG Chao ACTA NEUROPHARMACOLOGICA 2021, 11 (1): 1-64. DOI:10.3969/j.issn.2095-1396.2021.01.001 Abstract（ 154） PDF（4325KB）（ 32） Objective：To investigate the change and effect of P38 MAPK in rhabdomyolysis-induced acute kidney injury （AKI） and the interfered effect of betulinic acid （BA）. Methods：40 Wistar rats were randomly divided into 5 groups：control group（ C），group AKI（ A），group AKI+BA（ AB），group AKI+SB203580（ AS），group AKI+BA+SB203580（ ABS）. The experimental model of rhabdomyolysis-induced AKI was established by injecting 50% glycerin intramuscular into the hind limbs. Group AB，AS and ABS were administered intraperitoneally with BA and SB203580 separately or together. 24 hours after glycerin injection，the venous blood and kidney samples were taken. The serum creatinine（ CR），blood urea nitrogen（ BUN） and creatine kinase（ CK） were detected with automatic biochemistry analyzer. The expression of pP38 MAPK，P38 MAPK and cleaved caspase-3 in kidney were assayed by Western Blot. The pathological changes were examined by H&E staining. The levels of TNFα and IL6 in kidney were measured by ELISA. Results：Glycerin injection induced acute injury and pP38/P38 ratio was higher in the kidney，which were ameliorated by administration of BA and SB203580. In the dosage of this experiment，BA had better curative effect on renal function，kidney injury score，apoptosis rate and IL-6 level than SB203580. But the inhibition of P38 phosphorylation of SB203580 was stronger than BA. The influence on TNF-α of both drugs were similar. Generally，combined treatment of the two drugs had no significant difference with BA alone. Conclusion：In rhabdomyolysis-induced AKI，P38 MAPK was activated. Inhibition of P38 phosphorylation by SB203580 could reduce the level of Cr and BUN，suppress renal inflammation，alleviate the pathological damage and apoptosis. BA played a renoprotective role at least partially through inhibit ing the phosphorylation of P38 MAPK. Related Articles|Metrics

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Research Methods of Drug in Vitro Liver Metabolism LI Lan, ZHANG Dan-shen ACTA NEUROPHARMACOLOGICA 2020, 10 (4): 10-13. DOI:10.3969/j.issn.2095-1396.2020.04.003 Abstract（ 153） PDF（1131KB）（ 31） In vitro metabolism research is of great significance to elucidate the substance basis and mechanism of action of drugs. Common in vitro liver metabolism research methods include liver microsome in vitro warming method，hepatocyte in vitro warming method，liver perfusion technology，liver tissue sectioning technology，gene recombinant P450 enzyme system，etc. The liver metabolism of drugs in vitro cannot fully reflect the comprehensive metabolism of drugs in the body，and there is a difference from the actual metabolism in the body. In the future，it is necessary to combine in vivo experiments and other methods to improve the study of drug metabolism and transport in and out of the body；In vitro liver metabolism research methods such as the P450 enzyme system have high requirements on equipment，experimental operation costs，and data processing technology. Their application and promotion are still subject to certain constraints and restrictions. In the future，simple，fast，economical，and efficient scientific and technical methods and means need to be established. Because the liver metabolism of drugs in vitro has a huge role in promoting the research and development of new drugs and correctly guiding clinical co-administration，this article will focus on them. Reference|Related Articles|Metrics

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A Preliminary Study on the Effect of 5-HT2A/D2 Receptor Balancing Antagonist NH809 on Schizophrenia YU Min-quan, XU Xiang-qing ACTA NEUROPHARMACOLOGICA 2022, 12 (3): 1-. DOI:10.3969/j.issn.2095-1396.2022.03.001 Abstract（ 74） PDF（1284KB）（ 31） Objective：To investigate the pharmacological effects of 5-HT2A/D2 receptor balancing antagonist NH809 on schizophrenia in vivo. Methods：The effects of NH809 on schizophrenia in vivo were evaluated by MK-801 hydrogen maleat（0.3 mg·kg -1，ip） induced hyperactivity model in mice，apomorphine （1 mg·kg -1，sc） induced climbing model in mice and conditioned avoidance response（CAR） in rats，and compared with risperidone. Results：NH809 had dose-dependent inhibitory effect on MK-801 hydrogen maleate induced high activity model，apomorphine-induced climbing behavior in mice and conditioned avoidance response in vivo，with ED50 of 0.04，0.05 and 0.24 mg·kg -1，respectively. The ED50 of risperidone in these three models were 0.06，0.68 and 0.60 mg·kg -1，respectively. Conclusion：NH809 has significant pharmacological effects on several animal models of schizophrenia，and its activity in vivo is better than risperidone. Related Articles|Metrics

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Research Progress of High-Fat Diet and Alzheimer’s Disease HUANG Ying, HUO Yan-li, MING Yue, HAO Jun-rong ACTA NEUROPHARMACOLOGICA 2020, 10 (6): 54-59. DOI:10.3969/j.issn.2095-1396.2020.06.010 Abstract（ 124） PDF（1104KB）（ 30） High-fat diet plays an important role in the pathogenesis of AD. This paper reviews the possible pathogenesis of Alzheimer’s disease in recent years，and further expounds the possible mechanism of high fat diet causing Alzheimer’s disease:High fat diet increases the content of saturated free fatty acids in plasma and speeds up the pathological process of AD;High fat diet promotes the occurrence of AD by influencing blood lipid levels;A high-fat diet will lead to the production of large amounts of fat and cause chronic inflammation，the inflammatory factors produced cross the blood-brain barrier and stimulate neuroinflammatory cells;High-fat food will affect the gut bacteria，which in turn affect the microbiota - brain - gut axis，then lead to the AD. Based on the above mechanisms，we can treat or prevent AD by reducing free saturated fatty acids，regulating lipid metabolism disorders，improving inflammation，and regulating intestinal flora. Related Articles|Metrics

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Research Progress of Cortical Spreading Depression ZHAO Bo, YU Ai-mei, ZOU Yu-an ACTA NEUROPHARMACOLOGICA 2022, 12 (3): 28-. DOI:10.3969/j.issn.2095-1396.2022.03.006 Abstract（ 84） PDF（1210KB）（ 27） Cortical spreading depression is an inhibitory band of electrical activity generated after the cerebral cortex is stimulated. This inhibitory band can rapidly destroy and depolarize the concentration gradient of transmembrane ions in the cerebral cortex，resulting in short circuits inside and outside cells，which can affect brain perfusion and metabolism.resulting in a poor prognosis. This paper will summarize the research progress of CSR from the following aspects. Related Articles|Metrics

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Research Progress of Epigallocatechin Gallate ZENG Lu, ZHANG Shuai, AI Jing ACTA NEUROPHARMACOLOGICA 2021, 11 (1): 38-56. DOI:10.3969/j.issn.2095-1396.2021.01.006 Abstract（ 85） PDF（1847KB）（ 26） Epigallocatechin gallate (EGCG) , the main component of tea polyphenols, is a catechin monomer isolated from tea. It has a variety of biological activities such as antioxidation, anti-inflammation, anti-tumor, anti-metabolic diseases, cardiovascular and neuronal protective effects. In recent years, more and more studies related to the in vivo activity and medicinal values of EGCG have revealed that it may have important clinical application values. Therefore, this paper reviewed the advances in pharmacokinetics，pharmacology and toxicology of EGCG, so as to provide theoretical basis for the further development and utilization of EGCG. Related Articles|Metrics

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Research Progress on Protein Structure of Membrane Channels Permeable to Urea#br# XIONG Meng-yao, YANG Baoxue ACTA NEUROPHARMACOLOGICA 2021, 11 (1): 57-64. DOI:10.3969/j.issn.2095-1396.2021.01.007 Abstract（ 80） PDF（1003KB）（ 26） The transport of urea by membrane channel proteins is the main transport mode except free diffusion, which mediates the transport of urea between cells and organelles. These membrane channels transport urea selectively, and play important roles in the multiple physiological functions.In recent years, significant advances have been made in the structural biology of some urea-permeable membrane channels, detailing their molecular structure, physiological function and regulatory modification. These studies provide a theoretical basis for elucidating the close relationship between urea transport and related diseases, and greatly promoting the research and development of new drugs. Related Articles|Metrics

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Advances in Pharmacological Effects of Chrysophanol YUAN Xin-ru, ZHANG Dan-shen ACTA NEUROPHARMACOLOGICA 2020, 10 (6): 34-40. DOI:10.3969/j.issn.2095-1396.2020.06.006 Abstract（ 115） PDF（1111KB）（ 25） Chrysophanol is one of the effective monomers of anthraquinones that extracted from traditional Chinese medicine. It exists in the form of free aglycon in rhubarb，fleeceflower root，polygonum cuspidatum，cassia，pinellia，etc. Studies have found that chrysophanol has good pharmacological activities in neuroprotection，anti-oxidation，anti-cancer，anti-inflammatory，antibacterial and anti-virus，and promotion of fat metabolism. Although there are many studies on the pharmacological activity of chrysophanol，the overall review of it is relatively few. This article provides a comprehensive review of the pharmacological effects of chrysophanol，and provides valuable references for further research and clinical applications. Related Articles|Metrics

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Research Progress on Related Mechanisms of Cerebral Ischemia-Reperfusion Injury LI Zhao-zhen, ZHANG Dan-shen ACTA NEUROPHARMACOLOGICA 2020, 10 (6): 60-63. DOI:10.3969/j.issn.2095-1396.2020.06.011 Abstract（ 91） PDF（1018KB）（ 24） Cerebral ischemia-reperfusion injury can affect the outcome of the patient’s disease，even life-threatening. At present，the pathogenesis of cerebral ischemia-reperfusion injury includes inflammatory response，excitatory amino acid toxicity，intracellular calcium overload，free radical damage，energy metabolism disorder and cell apoptosis，etc. Many mechanisms influence each other and are complicated. This article summarizes the research on several main mechanisms of cerebral ischemia-reperfusion injury in recent years，and provides a basis for exploring and improving the research of cerebral ischemia-reperfusion injury. Related Articles|Metrics

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Recent Advances in the Research of the Nutritive and Active Components of Common Mushrooms DONG Xue-yuan, WANG Zhi-bao ACTA NEUROPHARMACOLOGICA 2020, 10 (3): 37-41. DOI:10.3969/j.issn.2095-1396.2020.03.007 Abstract（ 64） PDF（1016KB）（ 24） Mushroom belongs to fungus，some of which are edible，delicious，soft and glutinous meat，high nutritional value，and has a certain role in health care，is a kind of green health food. Due to different growth environments，there are many kinds of mushrooms，which are rich in proteins，amino acids，scarbohydrate，lipids，cellulose，vitamins，minerals and other components，and have a very high development value. Reference|Related Articles|Metrics

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Study on the Mechanism of Radix Paeoniae Rubra on Hepatocellular Carcinoma Based on Network Pharmacology YOU Si-han, BAI Jing-ru, WANG Zhi-bao, TAN Xiao-hong, GUO Chun-yan ACTA NEUROPHARMACOLOGICA 2020, 10 (6): 1-12. DOI:10.3969/j.issn.2095-1396.2020.06.001 Abstract（ 108） PDF（11223KB）（ 23） Objective:To predict the mechanism of Radix Paeoniae Rubra in the treatment of hepatocellular carcinoma(HCC)by network pharmacology.Methods:Through TCMSP database(https://tcmspw.com/tcmspsearch.php)，the chemical constituents of Radix Paeoniae Rubra were searched，and the targets of Radix Paeoniae Rubra were predicted by STD database and SEA database. Through OMIM database(http://www.omim.org)，drugbank database(https:// www.drugbank.ca/)and TTD database(http://db.idrblab.net/ttd/)，the corresponding targets of HCC were collected. Then, the common targets from both active ingredient targets and HCC disease targets were obtained. The String platform was used to collect liver cancer disease-related target proteins, and GO analysis was performed with David database. Protein-protein interaction (PPI) network was constructed by Cytoscape 3.2.1 software, and the core targets were obtained by topological analysis. The mechanism of Radix Paeoniae Rubra on HCC was further analyzed.Results:A total of 28 compounds and 442 targets from Radix Paeoniae Rubra were obtained from TCMSP database. A total of 148 HCC-related disease targets were retrieved from OMIM, DrugBank and TTD databases. Twenty-three common targets from both active ingredient targets and HCC disease targets were obtained. There were 193 nodes and 722 edges in the protein- protein interaction network，and 95 nodes，439 edges and 21 core targets were obtained by topological index screening. A total of 561 biological processes，85 cellular components and 130 molecular functions were obtained by GO annotation.Conclusion:Network pharmacology intuitively shows that Radix Paeoniae Rubra has multiple components，multiple targets and multiple pathways in the treatment of HCC. This study provides a theoretical basis for the follow-up development of medicines for the treatment of HCC. Related Articles|Metrics

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Studies on the Role of Focal Adhesion Kinase in Diseases HE Jin-zhao, YANG Bao-xue ACTA NEUROPHARMACOLOGICA 2021, 11 (3): 50-64. DOI:10.3969/j.issn.2095-1396.2021.03.009 Abstract（ 86） PDF（1251KB）（ 22） Focal adhesion kinase （FAK） as a crucial component of focal adhesions （FAs） plays an important role in intracellular and extracellular signal transduction. FAK is a non-receptor tyrosine kinase and mainly regulated by integrins，growth factors and G-protein-coupled receptors，which mediates various bioactivities，such as cell migration，invasion，proliferation，differentiation and angiogenesis. A wide array of studies have demonstrated that abnormal expression and activation of FAK were critically involved in the pathogenesis of cardiovascular diseases，hepatic and renal injuries，lipometabolism，immunoregulation and cancer，in which were closely related to poor prognosis. In recent years，with the development of FAK animal models and inhibitors，targeting FAK has been recognized as new treatment for diseases. Most FAK inhibitors show promising preclinical effect without significant adverse effect and several are undergoing clinical trials. This review summarizes the studies on the role of FAK in diseases and related animal models and inhibitors to clarify the underlying mechanism and therapeutic prospect. Related Articles|Metrics

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Clinical Observation on Emotion, Cognition and Abnormal Sensation of Limbs in Parkinson’s Disease combinde with Type 2 Diabetes Mellitus PAN Yan-ting, ZHANG Xiao-jie, FAN Lei, LIU Xing-liang, YUE Bing-hong ACTA NEUROPHARMACOLOGICA 2021, 11 (4): 1-. DOI:10.3969/j.issn.2095-1396.2021.04.001 Abstract（ 79） PDF（1082KB）（ 20） Objective：To study the emotion，cognition and abnormal sensation of limbs in Parkinson’s disease combined with type 2 diabetes mellitus.Methods：Forty patients with Parkinson’s disease without diabetes were selected as control group，and forty patients with Parkinson’s disease combined with type 2 diabetes mellitus were selected as observation group in the same period. Analysis the difference in emotion，cognition and abnormal sensation of limbs between the control group and observation group.Results：The result of emotion and cognition showed that the incidence of memory loss，inattention and apathy was singnificantly higher in observation group than control group（P<0.05）. The sensation symptoms of limbs showed that limb pain and limb cold was singnificantly higher in observation group than control group（P<0.05）.Conclusion：The incidence rate of emotion，cognitive impairment，numbness and cold symptoms in Parkinson’s patients with type 2 diabetes was higher than that in PD patients without diabetes. Related Articles|Metrics

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Effects of Osthole on Cortical Neurotransmitters and the Anxietyand Depresion-Like Behaviors in the Oxytocin Receptor-Silencing Rats#br# FAN Xukun, SUN Yi, SONG Shuangshuang, CONG Yifan, HOU Xueqin ACTA NEUROPHARMACOLOGICA 2021, 11 (1): 11-17. DOI:10.3969/j.issn.2095-1396.2021.01.002 Abstract（ 78） PDF（1373KB）（ 19） Objective: To explore the role of oxytocin receptor (OTR) in regulating anxiety- and depression-like behaviors and monoamine, amino acids and choline neurotransmitters in the cerebral cortex. And to investigate the effects of osthole on neurotransmitters in OTR silencing rats.Method: OTR silencing rats were established via short hairpin RNA (shRNA). Elevated plus maze and forced swimming test were used to observe the effect of osthole on anxiety- and depression-like behaviors. Q-orbitrap HPLC-HRMS was applied to detect neurotransmitters in the cerebral cortex of rats.Results: In the elevated plus maze, the number of entering the open arms and the residence time in the open arms were significantly reduced in the OTR-shRNA rats compared with the control group (P<0.05). Osthole (12.5 mg·kg-1) treatment increased the number of entering the open arms and the residence time in the open arms compared with the OTR-shRNA group (P<0.01). Forced swimming test showed that the OTR-shRNA group rats were immobile for longer than the control group (P<0.05). The immobile time in the osthole (12.5 mg·kg-1and 25 mg·kg-1) groups were reduced than that in the OTR-shRNA group (P<0.05). Compared with the control group, the levels of dopamine (DA) and L-glutamic acid in the cerebral cortex of the OTR-shRNA group were higher (P<0.05), and the levels of 5-hydroxytryptamine (5-HT), gamma aminobutyric acid (GABA), and acetylcholine (Ach) were significantly lower (P<0.05). Osthole (12.5 mg·kg-1) reduced the level of DA, and increased the level of 5-HT, GABA and Ach (P<0.05), whereas osthole (25 mg·kg-1) increased the level of 5-HT and Ach (P<0.05).Conclusions:Osthole could influence neurotransmitters in the cerebral cortex, and attenuate anxiety- and depression-like behaviors, which may be through regulating the OTR pathway. It provides a new direction and basis for the research in central nervous system disorders, such as depression. Related Articles|Metrics