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Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of monoamine neurotransmitter

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Chinese Journal of Integrative Medicine 2022年第7期28卷 586-593页

作者： JIANG Bing WU Ruo-ming LI Hai-dong LI Kun LI Hui DANG Wen-zhen FENG Gui-ze BAO Wei-lian YE Guan SHEN Xiao-yan Department of Pharmacology School of PharmacyFudan UniversityShanghai 200120China Department of Pharmacology of Chinese Materia Medica School of Traditional Chinese MedicineGuangdong Pharmaceutical UniversityGuangzhou 510006China Central Research Institute Shanghai Pharmaceuticals Holding Co.Ltd.Shanghai 200120China

Objective: To investigate the therapeutic effect of Yixin Ningshen Tablet(YXNS) on comorbidity of myocardial infarction(MI) and depression in rats and explore the underlying mechanism. Methods: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights,including control, model, fluoxetine(FLXT, 10 mg/kg), low-dose YXNS(LYXNS, 100 mg/kg), and high-dose YXNS(HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction(MI) area and myocardial apoptosis was also detected. Serum levels of interleukin(IL)-6, IL-1β, tumor necrosis factor-α(TNF-α), 5-hydroxytryptamine(5-HT), adrenocorticotrophic hormone(ACTH), corticosterone(CORT), and norepinephrine(NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5’-monophosphate-activated protein kinase(AMPK), p-AMPK,peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), and nuclear respiratory factor 1(NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase(IDO1), kynurenine 3-monooxygenase(KMO), and kynureninase(KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. Results: Compared with the model group,the cardiac function of rats treated with YXNS significantly improved(P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats(P<0.01 or P<0.05), promoted AMPK phosphorylation,and increased PGC-1α protein expression(P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH,and CORT(all P<0.05). Moreover, HYXNS decreased the m RNA expressions of I

关键词： Yixin Ningshen Tablet depression cardiovascular disorders inflammatory factor monoamine neurotransmitter kynurenine pathway Chinese medicine

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Altered serous levels of monoamine neurotransmitter metabolites in patients with refractory and non-refractory depression

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Neural Regeneration Research 2012年第14期7卷 1113-1118页

作者： Guiqing Zhang Yanxia Zhang Jianxia Yang Min Hu Yueqi Zhang Xia Liang Department of Rehabilitation and Psychology the First Affiliated Hospital of Shihezi University Medical College Shihezi 832008 XinjiangUygur Autonomous Region China

The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression （TRD） and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.

关键词： treatment-resistant depression monoamine neurotransmitter 5-hydroxyindoleacetic acid 3-methoxy-4-hydroxyphenyl ethylene glycol homovanillic acid

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Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism

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Journal of Integrative Medicine 2023年第2期21卷 205-214页

作者： Nan Zhang Shu-ting Wang Lei Yao School of Design Shanghai Jiao Tong UniversityShanghai 200000China School of Agriculture and Biology Shanghai Jiao Tong UniversityShanghai 200000China

Objective:Anxiety is one of the most common symptoms associated with autistic spectrum disorder.The essential oil of Cananga odorata(Lam.)Hook.f.&Thomson,usually known as ylang-ylang oil(YYO),is often used in aromatherapy as a mood-regulating agent,sedative,or hypotensive agent.In the present study,the effects and mechanisms of YYO in alleviating anxiety,social and cognitive behaviors in autism-like rats were investigated.Methods:The prenatal valproic acid(VPA)model was used to induce autism-like behaviors in offspring rats.The effectiveness of prenatal sodium valproate treatment(600 mg/kg)on offspring was shown by postnatal growth observation,and negative geotaxis,olfactory discrimination and Morris water maze(MWM)tests.Then three treatment groups were formed with varying exposure to atomized YYO to explore the effects of YYO on the anxiety,social and cognitive behaviors of the autistic-like offspring through the elevated plus-maze test,three-chamber social test,and MWM test.Finally,the monoamine neurotransmitters,including serotonin,dopamine and their metabolites,in the hippocampus and prefrontal cortex(PFC)of the rats were measured using a high-performance liquid chromatography.Results:Offspring of VPA exposure rats showed autism-like behaviors.In the VPA offspring,mediumdose YYO exposure significantly elevated the time and entries into the open arms in the elevated plusmaze test,while low-dose YYO exposure significantly enhanced the social interaction time with the stranger rat in session 1 of the three-chamber social test.VPA offspring treated with YYO exposure used less time to reach the platform in the navigation test of the MWM test.YYO exposure significantly elevated the metabolism of serotonin and dopamine in the PFC of VPA offspring.Conclusion:YYO exposure showed the effects in alleviating anxiety and improving cognitive and social abilities in the offspring of VPA exposure rats.The role of YYO was related to the regulation of the metabolism of serotonin and dopamine.

关键词： Cananga odorata essential oil autism-like rat anxiety social behavior monoamine neurotransmitter

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Bone marrow-derived mesenchymal stem cells ameliorate sodium nitrite-induced hypoxic brain injury in a rat model

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Neural Regeneration Research 2017年第12期12卷 1990-1999页

作者： Elham H.A.Ali Omar A.Ahmed-Farid Amany A.E.Osman Faculty of Women for Art Sciences and Education Ain Shams University Cairo Egypt National Organization for Drug Control and Research (NODCAR) Giza Egypt

Sodium nitrite（Na NO2） is an inorganic salt used broadly in chemical industry. Na NO2 is highly reactive with hemoglobin causing hypoxia. Mesenchymal stem cells（MSCs） are capable of differentiating into a variety of tissue specific cells and MSC therapy is a potential method for improving brain functions. This work aims to investigate the possible therapeutic role of bone marrow-derived MSCs against Na NO2 induced hypoxic brain injury. Rats were divided into control group（treated for 3 or 6 weeks）, hypoxic（HP） group（subcutaneous injection of 35 mg/kg Na NO2 for 3 weeks to induce hypoxic brain injury）, HP recovery groups N-2 w R and N-3 w R（treated with the same dose of Na NO2 for 2 and 3 weeks respectively, followed by 4-week or 3-week self-recovery respectively）, and MSCs treated groups N-2 w SC and N-3 w SC（treated with the same dose of Na NO2 for 2 and 3 weeks respectively, followed by one injection of 2 × 106 MSCs via the tail vein in combination with 4 week self-recovery or intravenous injection of Na NO2 for 1 week in combination with 3 week self-recovery）. The levels of neurotransmitters（norepinephrine, dopamine, serotonin）, energy substances（adenosine monophosphate, adenosine diphosphate, adenosine triphosphate）, and oxidative stress markers（malondialdehyde, nitric oxide, 8-hydroxy-2′-deoxyguanosine, glutathione reduced form, and oxidized glutathione） in the frontal cortex and midbrain were measured using high performance liquid chromatography. At the same time, hematoxylin-eosin staining was performed to observe the pathological change of the injured brain tissue. Compared with HP group, pathological change of brain tissue was milder, the levels of malondialdehyde, nitric oxide, oxidized glutathione, 8-hydroxy-2′-deoxyguanosine, norepinephrine, serotonin, glutathione reduced form, and adenosine triphosphate in the frontal cortex and midbrain were significantly decreased, and glutathione reduced form/oxidized glutathione and adenosine monophosphate/adenosine triphosphate ratio were significantly increased

关键词： nerve regeneration hypoxia bone marrow-derived mesenchymal stem cells sodium nitrite monoamine neurotransmitter cell energy neural regeneration

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Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

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Neural Regeneration Research 2012年第3期7卷 191-196页

作者： Shuang Liang Renbin Huang Xing Lin Jianchun Huang ZhongshiHuang Huagang Liu Department of Pharmacology College of Pharmacy Guangxi Medical University Nanning 530021 Guangxi Zhuang Autonomous RegionChina

The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide （YLSPS; 150, 300 and 600 mg/kg） for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS （300 and 600 mg/kg）, monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.

关键词： Yulangsan polysaccharide anti-depressant chronic stress monoamine neurotransmitter adenylate cyclase brain-derived neurotrophic factor Chinese medicine neural regeneration

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Effects of Fuhe decoction on behaviors and monoamine neurotransmitters in different brain regions of CUMS combined with social isolation depression model rats

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Journal of Traditional Chinese Medical Sciences 2020年第3期7卷 245-254页

作者： Ruoyun Zheng Weifeng Xiong Juan He Xu Wang Ranran Wang Yu Hao School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing100029China

Objective:To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation(CUMS)combined with social isolation.Methods:Fifty male SD rats were randomly divided into a blank group,model group,fluoxetine group,Chaiqinwendan decoction group,and Fuhe decoction group.Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model.After 42 days of administration,a tail suspension test and high-performance liquid electrochemical detection(HPLC-ECD)were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine(NE),dopamine(DA),5-hydroxytrytamine(5-HT),and metabolites in different brain regions of rats in each group before and after treatment.Results:Compared with the model group,the epinephrine(E)content in the Fuhe decoction group was highly significantly increased(P<.01).Compared with the model group,the 5-HT content of the prefrontal cortex in rats in the Fuhe decoction group was highly significantly increased(P<.01).Furthermore,compared with the model group,the 5-HT content in the hippocampus of rats in the Fuhe decoction group was significantly increased(P<.05).Conclusion:Fuhe decoction can improve the depression-like behaviors of model rats,and its antidepressant effect may be related to the increase in 5-HT content in the prefrontal cortex and hippocampus of rats.

关键词： Yunqi recipes Fuhe decoction Depression CUMS monoamine neurotransmitter

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Antipyretic Effect and Action Mechanism of Jinzhen Oral Liquid

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Medicinal Plant 2022年第1期13卷 67-70,76页

作者： Qian HONG Xiaofeng YUAN Qing WANG Yan ZHAO The Affiliated Huaihai Hospital of Xuzhou Medical University Xuzhou 221004 China The 71st Group Army Hospital of CPLA Army Xuzhou 221004 China Xuzhou New Health Hospital Xuzhou 221000 China

[Objectives]To investigate the antipyretic effect and action mechanism of Jinzhen Oral Liquid.[Methods]The yeast-induced fever model was used to determine the rectal temperature of rats at 6,8,and 10 h after yeast injection.The contents of IL-6 and TNF-αin the rat serum and the contents of 5-HT and NE in the hypothalamus were detected by radioimmunoassay;the model of yeast-induced fever in rat was established by intraperitoneal injection of lipopolysaccharide(LPS),rectal temperature of the rats was determined,the contents of TNF-αand IL-1βin serum,cyclic adenosine monophosphate(cAMP)and prostaglandin E2(PGE2)in hypothalamus were detected by radioimmunoassay.[Results]After the intervention of Jinzhen Oral Liquid,the body temperature of rats in the yeast-induced fever model was significantly reduced,the IL-6 and TNF-αcontents in serum were significantly reduced,the 5-HT content in the hypothalamus was significantly reduced,while the NE content was significantly increased;after 2 h of intraperitoneal injection of LPS,the body temperature of the model rats increased significantly;after the intervention of Jinzhen Oral Liquid,the increase in rectal temperature of LPS-induced fever model rats decreased,and the TNF-αand IL-1βcontents in serum and cAMP and PGE2 contents in hypothalamus of model rats were significantly decreased.[Conclusions]Jinzhen Oral Liquid has a significant antipyretic effect,and its action mechanism may be related to reducing the inflammatory factors in the serum,thereby inhibiting the generation of pyrogenic media in the hypothalamus.

关键词： Antipyretic effect Lipopolysaccharide(LPS) Jinzhen Oral Liquid monoamine neurotransmitter Cyclic adenosine monophosaphate(CAMP) Prostaglandin E_(2)(PGE_(2))

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Inhibitory effect of baicalein on mice tremor induced by oxotremorine and mechanisms

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中国药理学与毒理学杂志 2017年第10期31卷 1007-1007页

作者： Yu-lin YANG Xue ZHANG Shu-mei WANG Guan-hua DU Guangdong Pharmaceutical University Guangzhou 510006 Chin Beijing Key Laboratory of Drug Target Research and Drug Screening Institute of Materia Medica Chinese Academy of Medical Sciences Beijing 100050 China

OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine,and the latency,duration and frequency of muscle tremor in mice were measured immediately;the saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function;the aim of this study was to determine the content of MDA and the activity of GSH-PX,and to investigate the anti-oxidation of mice with tremor model.The activity of acetylcholinesterase(AchE)and acetylcholine transferase(ChA T)can indirectly reflect the level of acetylcholine in the brain.The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography(HPLC-ECD).RESULTS The animals in the model group appeared obvious tremoring,salivating and erecting and other symptoms.Compared to the model group,there was no obvious inhibitory effect on the administration of each dose.After 7,14,21 and 28 d of continuous administration,the latency,duration and tremor frequency of tremor mice were significantly shortened,the levels of acetylcholine were significantly decreased,the changes of DOPAC and DA neurotransmitters in the brain of model group were recovered,regulate the dynamic balance of acetylcholine and dopamine in the brain.CONCLUSION Long-term administration can improve the tremor behavior of mice,the mechanismmay be related to the regulation of neurotransmittersin brain.

关键词： baicalein oxotremorine acetylcholine monoamine neurotransmitter HPLC-ECD

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Antidepressive Effects and Possible Therapeutic Basis of Xiaochaihutang

Antidepressive Effects and Possible Therapeutic Basis of Xia...

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第十四届全国中药和天然药物学术研讨会

作者： Kuo Zhang Fang Wang Yingxu Dong Lljuan Wang Huanhuan Pang Guangyue Su Jie Ma Zhili Xiong Jingyu Yang Chunfu Wu Shenyang Pharmaceutical University

Aim Xiaochaihutang（XCHT）,a famous Chinese herbal formula,has been used clinically in depressive disorders.Our previous study has demonstrated that XCHT has therapeutic actions on depressive-like behavior induced by chronic unpredictable mild stress in rats,which is mediated by increasing the monoamine neurotransmitter concentration and neurotrophin expression.However,the therapeutic basis of XCHT on treating depression is unclear.The aim of present study is to provide deeper insights into therapeutic mechanisms of antidepressive effects of XCHT and its main components.Methods The core in compatibility of XCHT on antidepressive effect was evaluated by using orthogonal array design.Antidepressive effects of XCHT and its core in compatibility were comparatively evaluated by tail suspension test（TST） and forced swim test（FST）.Levels of monoamine neurotransmitter were detected by HPLE-ECD and serum corticosterone was also measured by Elisa kit.Results In orthogonal array design,taking immobility time as index,one-way ANOVA indicated that Radix Scutellariae,Ginseng and Radix glycyrrhizae,which were named HRG,might be the core in compatibility of XCHT.Oral administration of both XCHT and HRG for 15 days significantly reduced the immobility time in TST and FST.In addition,XCHT and HRG significantly increased levels of 5-HT,DA and DOPAC in hypothalamus and reduced the level of serum corticosterone in mice exposed to FST.Conclusion:HRG is the core in compatibility of XCHT on anti-depression.XCHT and HRG exert antidepressivet effects via regulating monoamine neurotransmitter and neuroendocrine HPA axis system.

关键词： Xiaochaihutang antidepression compatibility monoamine neurotransmitter HPA axis.

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