Study on Urinary Metabolomics of Premenstrual Dysphoric Disorder Patients with Liver-qi Depression Syndrome Treated with Xiaoyaosan Study Protocol Clinical Trial (SPIRIT Compliant) | Chapter 14 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

 Introduction: Premenstrual dysphoric disorder (PMDD) is a serious form of premenstrual syndrome with mental symptoms as its main manifestation, which seriously affects women's health and daily life. Some basic research and clinical studies have shown that the Chinese herbal medicine of Xiaoyaosan can relieve the symptoms of mental disorders with few side effects. The aim of this study is to evaluate the clinical efficacy of Xiaoyaosan for treating PMDD with liver-qi depression syndrome. In addition, metabonomics and small molecular marker compounds closely related to the pathogenesis of PMDD are expected to be found, and mechanism of Xiaoyaosan is further explored from the metabolic level.

Methods and Analysis: This study is a clinical pilot trial. Thirty PMDD patients with liver-qi depression syndrome and thirty healthy participants will be recruited. Study participants will be assigned in a 1:1 ratio to 2 groups: a normal control group and Xiaoyaosan treatment group. The treatment group will receive the Chinese patent medicine of Xiaoyaosan for 3 menstrual cycles. The primary outcome is the syndrome change in the Daily Record of Severity of Problems (DRSP). The secondary outcome is improvement in TCM syndrome, which will be measured with TCM symptom score scale. Urine metabolism profiles of participants by liquid chromatograph-mass spectrometer (LC-MS) method will be measured to explore the mechanism of PMDD pathogenesis and action of Xiaoyaosan on PMDD.

Discussion: This trial will evaluate the effectiveness and the therapeutic mechanism from the metabolomics level of Xiaoyaosan in individuals with PMDD. If successful, the outcome of this trial will provide a viable treatment option for PMDD patients and objective evidence on the efficacy of Xiaoyaosan for PMDD.

Ethics and Dissemination: The trial has been approved by the Institutional Ethics Committee of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine (file number: DZMEC-KY-2019-73). Written informed consent will be obtained from all participants. The results of the study will be published in peer-reviewed journals or communicated via yearly reports to funding bodies.

Trial registration: Chinese Clinical Trial Registry, ChiCTR1900026296.

Author(s) Details:

Mengbai Xu,
School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China and Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Yanfeng Liu,
Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Yu Guo,
School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.

Chenyue Liu,
School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Yueyun Liu,
School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Zhiyi Yan,
School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Yajing Hou,
School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Xiaojuan Li,
School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.

Qingyu Ma,
School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
 
Xuan Zhou,
School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
 
Liuqing Liu,
Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
 
Sheng Huang,
Jiuzhitang Co., Ltd., Changsha, China.
 
Jiaxu Chen,
School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China and Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11277

Xiaoyaosan Exerts Anxiolytic-like Effects by Down-regulating the TNF-α/JAK2-STAT3 Pathway in the Rat Hippocampus | Chapter 13 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

 Although the anxiolytic-like effects of Xiaoyaosan, a Chinese herbal formula, have been described in many previous studies, its underlying mechanism remains undefined. The cytokine tumour necrosis factor- α (TNF- α) and its closely associated janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT3) signalling pathway regulate the neuro-inflammatory response in the brain, thus participating in the development of anxiety. Our purpose was to investigate whether the anxiolytic-like effects of Xiaoyaosan are related to the TNF- α/JAK2-STAT3 pathway in the hippocampus. We examined the effects of Xiaoyaosan on behaviours exhibited in the elevated plus maze test, open field test and novelty-suppressed feeding test as well as hippocampal neuron damage and changes in the TNF- α/JAK2-STAT3 pathway in a rat model of chronic immobilization stress (CIS)-induced anxiety. Xiaoyaosan exerts anxiolytic-like effects on CIS-induced anxiety, with a significant alleviation of anxiety-like behaviours, an attenuation of hippocampal neuron damage, and a reversal of the activation of the TNF- α/JAK2-STAT3 pathway in the hippocampus that are similar to the effects of the JAK2 antagonist AG490. However, Xiaoyaosan and AG490 failed to effectively regulate apoptosis-related factors, including Bax and Caspase-3. These results suggest that Xiaoyaosan attenuates stress-induced anxiety behaviours by down-regulating the TNF- α/JAK2-STAT3 pathway in the rat hippocampus.

Author(s) Details:

Xiao-Juan Li,
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.,

Qing-Yu Ma,
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

You-Ming Jiang,
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Xiao-Hui Bai,
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Zhi-Yi Yan,
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Qun Liu,
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Qiu-Xia Pan,
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Yue-Yun Liu,
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Jiaxu Chen,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11276

Involvement of Normalized Glial Fibrillary Acidic Protein Expression in the Hippocampi in Antidepressant-Like Effects of Xiaoyaosan on Chronically Stressed Mice | Chapter 10 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

 The research has only yielded a partial comprehension of major depressive disorder (MDD) and the mechanisms underlying the antidepressant-like effects of Xiaoyaosan (XYS). Therefore, in this study, we aimed to explore the effects of XYS on chronic unpredictable mild stress- (CUMS-) induced changes in the neuronal and the astrocytic markers in the mouse hippocampus. The physical states and depressive-like behaviors in mice with CUMS were recorded. The serum contents of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured. The protein and mRNA expressions and the immunoreactivities of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) in mouse hippocampus were detected using a Western blot, qRT-PCR, and immunohistochemical staining, respectively. XYS treatment markedly improved the physical state and depressive-like behaviors in mice subjected to CUMS compared with the model group, and the serum contents of BDNF and GDNF were significantly upregulated. XYS treatment also elevated the protein and mRNA levels, as well as the immunoreactivity of GFAP in the hippocampus. However, CUMS did not influence NeuN expression. In conclusion, these results reveal that chronic administration of XYS elicits antidepressant-like effects in a mouse model of depression and may normalize glial fibrillary acidic protein expression in the hippocampi of mice with CUMS.

Author(s) Details:

Xiu-Fang Ding,
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing-100029, China.

Yan Liu,
Henan University of Chinese Medicine, Henan, China and School of Pre-Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, China.

Zhi-Yi Yan,
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing-100029, China.

Xiao-Juan Li,
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing-100029, China.

Qing-Yu Ma,
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing-100029, China.

Zhong-Ye Jin,
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing-100029, China.

Yan Liu,
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing-100029, China.

Yue-Hua Li,
Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Yue-Yun Liu,
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing-100029, China.
 
Zhe Xue,
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing-100029, China.
 
Jiaxu Chen,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China and Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.
 
Zhi-Ping Lv,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11271

Xiaoyaosan Ameliorates Chronic Immobilization Stress-Induced Depression-Like Behaviors and Anorexia in Rats: The Role of the Nesfatin-1-Oxytocin-Proopiomelanocortin Neural Pathway in the Hypothalamus | Chapter 9 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

Background: Chronic stress is an important risk factor for depression. The nesfatin-1 (NES1)-oxytocin (OT)-proopiomelanocortin (POMC) neural pathway, which is involved in the stress response, was recently shown to have an anorectic effect in the hypothalamus. Our previous study showed that Xiaoyaosan, a well-known antidepressant used in traditional Chinese medicine, effectively relieved appetite loss induced by chronic immobilization stress (CIS). However, whether Xiaoyaosan ameliorates depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway remains unclear.

Objective: To investigate whether the antidepressant-like and anti-anorexia effects of Xiaoyaosan are related to the NES1-OT-POMC neural pathway in the hypothalamus.

Methods: Rats were randomly divided into control, CIS, Xiaoyaosan treatment, and fluoxetine treatment groups. The rats in the CIS, Xiaoyaosan treatment, and fluoxetine treatment groups were subjected to CIS for 21 consecutive days, during which they were administered distilled water, a Xiaoyaosan decoction [3.854 g/(kg·d)] or fluoxetine [1.76 mg/(kg·d)], respectively, by gavage, and their body weights and food intake were monitored daily. The rats were subsequently subjected to the open field test and sucrose preference test. Then, the expression levels of corticosterone and NES1 in the serum and the expression levels of NES1, OT, POMC, and melanocortin-4 receptor (MC4R) in the hypothalamus were determined by real-time fluorescence quantitative polymerase chain reaction, Western blot analysis, and immunochemistry. Furthermore, immunofluorescence double staining was used to determine whether related proteins in the hypothalamic NES1-OT-POMC neural pathway were co-expressed.

Results: Compared to control rats, rats exposed to CIS exhibited gradually less food intake and lower body weights and significantly increased concentrations of NES1 in the serum and paraventricular nucleus. Moreover, the expression levels of POMC, OT, and MC4R in the hypothalamus were significantly higher in the CIS group than those in the control group. However, these changes were reversed by pretreatment with Xiaoyaosan and fluoxetine. Specifically, the expression levels of members of the NES1-OT-POMC neural pathway were lower in the Xiaoyaosan-treated group than in the CIS group.

Conclusion: Xiaoyaosan ameliorates CIS-induced depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway in the hypothalamus.

Author(s) Details:

Qingyu Ma,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Xiaojuan Li,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Zhiyi Yan,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Haiyan Jiao,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Tingye Wang,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Yajing Hou,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Youming Jiang,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Yueyun Liu,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Jiaxu Chen,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11270

Xiaoyaosan Exerts Antidepressant-like Effects by Regulating the Functions of Astrocytes and EAATs in the Prefrontal Cortex of Mice | Chapter 8 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

 Background: Mounting evidence indicates that the cerebral cortex is an important physiological system of emotional activity, and its dysfunction may be the main cause of stress. Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS), which initiates rapid signal transmission in the synapse before its reuptake into the surrounding glia, specifically astrocytes (ASTs). The astrocytic excitatory amino acid transporters 1 (EAAT1) and 2 (EAAT2) are the major transporters that take up synaptic glutamate to maintain optimal extracellular glutamic levels, thus preventing accumulation in the synaptic cleft and ensuing excitotoxicity. Growing evidence has shown that excitotoxicity is associated with depression. Therefore, we hypothesized that the underlying antidepressant-like mechanism of Xiaoyaosan (XYS), a Chinese herbal formula, may be related to the regulation of astrocytic EAATs. Therefore, we studied the antidepressant mechanism of XYS on the basis of EAAT dysfunction in ASTs.

Methods: Eighty adult C57BL/6 J mice were randomly divided into 4 groups: a control group, a chronic unpredictable mild stress (CUMS) group, a Xiaoyaosan (XYS) treatment group and a fluoxetine hydrochloride (Flu) treatment group. Except for the control group, mice in the other groups all received chronic unpredictable mild stress for 21 days. Mice in the control and CUMS groups received gavage administration with 0.5 mL of normal saline (NS) for 21 days, and mice in the XYS and Flu treatment groups were administered dosages of 0.25 g/kg/d and 2.6mg/kg/d by gavage. The effects of XYS on the depressive- like behavioral tests, including the open field test (OFT), forced swimming test (FST) and sucrose preference test (SPT), were examined. The glutamate (Glu) concentrations of the prefrontal cortex (PFC) were detected with colorimetry. The morphology of neurons in the PFC was observed by Nissl staining. The expression of glial fibrillary acidic protein (GFAP), NeuN, EAAT1 and EAAT2 proteins in the PFC of mice was detected by using Western blotting and immunohistochemistry. Quantitative real-time PCR (qPCR) was used to detect the expression of the GFAP, NeuN, EAAT1 and EAAT2 genes in the PFC of mice.

Results: The results of behavioral tests showed that CUMS-induced mice exhibited depressive-like behavior, which could be improved in some tests with XYS and Flu treatment. Immunohistochemistry and Western blot analysis showed that the protein levels of GFAP, NeuN, EAAT1 and EAAT2 in the PFC of CUMS mice were significantly lower than those in the control group, and these changes could be reversed by XYS and Flu. The results of qPCR analysis showed that the expression of GFAP, NeuN, EAAT1 and EAAT2 mRNAs in the PFC of CUMS mice was not significantly changed, with the exception of EAAT2, compared with that of the control group, while the expression of the above mRNAs was significantly higher in the XYS and Flu groups than that in the CUMS group.

Conclusion: XYS may exert antidepressant-like effects by improving the functions of AST and EAATs and attenuating glutamate-induced neuronal damage in the frontal cortex.

Author(s) Details:

Yan Liu,
School of Pre-clinical Medicine, Hubei University of Chinese Medicine, Wuhan-430065, China and School of Pre-clinical Medicine, Henan University of Chinese Medicine, Zhengzhou-450046, China.

Xiu-fang Ding,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Xin-xing Wang,
School of Pre-clinical Medicine, Henan University of Chinese Medicine, Zhengzhou-450046, China.

Xiao-juan Zou,
School of Pre-clinical Medicine, Hubei University of Chinese Medicine, Wuhan-430065, China.

Xiao-juan Li,
School of Pre-clinical Medicine, Hubei University of Chinese Medicine, Wuhan-430065, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Yue-yun Liu,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Jie Li,
School of Pre-clinical Medicine, Henan University of Chinese Medicine, Zhengzhou-450046, China.

Xiu-yun Qian,
School of Pre-clinical Medicine, Henan University of Chinese Medicine, Zhengzhou-450046, China.

Jiaxu Chen,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China and Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11269

Effects of Xiaoyaosan on the Hippocampal Gene Expression Profile in Rats Subjected to Chronic Immobilization Stress | Chapter 7 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

Objective: This study examined the effect of Xiaoyaosan and its anti-stress mechanism in rats subjected to chronic immobilization stress at the whole genome level.

Methods: Rat whole genome expression chips (Illumina) were used to detect differences in hippocampal gene expression in rats from the control group (CN group), model group (M group) and Xiaoyaosan group (XYS group) that were subjected to chronic immobilization stress. The Gene Ontology terms and signaling pathways that were altered in the hippocampus gene expression profile were analyzed. The network regulating the transcription of the differentially expressed genes was also established. To verify the results from the gene chips, real-time quantitative polymerase chain reaction was used to determine the expression of the GABRA1, FADD, CRHR2, and CDK6 genes in hippocampal tissues. In situ hybridization (ISH) and immunohistochemistry were used to determine the expression of the GABRA1 and CRHR2 genes and proteins, respectively.

Results: Compared with the CN group, 566 differentially expressed genes were identified in the M group. Compared with the M group, 544 differentially expressed genes were identified in the XYS group. In the M and XYS groups, multiple significantly upregulated or downregulated genes functioned in various biological processes. The cytokine receptor interaction pathway was significantly inhibited in the hippocampus of the model group. The actin cytoskeleton regulation pathway was significantly increased in the hippocampus of the XYS group. The inhibition of hippocampal cell growth was the core molecular event of network regulating the transcription of the differentially expressed genes in the model group. Promotion of the regeneration of hippocampal neurons was the core molecular event of the transcriptional regulatory network in the XYS group. The levels of the GABRA1, FADD, CRHR2 and CDK6 mRNAs, and proteins were basically consistent with the results obtained from the gene chip.

Conclusion: XYS may have the ability of resistance to stress, enhancement immunity and promotion nerve cell regeneration by regulating the expression of multiple genes in numerous pathways and repaired the stress-induced impairments in hippocampal structure and function by inducing cytoskeletal reorganization. These results may provide the possible target spots in the treatment of stress in rats with XYS.

Author(s) Details:

Xiao-Hong Li,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China and School of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning, China.

Xue-Ming Zhou,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China and School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China.

Xiao-Juan Li,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China and Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Yue-Yun Liu,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Qun Liu,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Xiao-Ling Guo,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Li-Qiang Yang,
School of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning, China.

Jiaxu Chen,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China and Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11268

Xiaoyaosan Improves Depressive-like Behavior in Rats with Chronic Immobilization Stress through Modulation of the Gut Microbiota | Chapter 6 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

 Depression has become the leading cause of disability worldwide and a growing public health problem in China. In addition, intestinal flora may be associated with depression. This study investigated the effect of the decoction Xiaoyaosan (XYS) against depressive behavior through the regulation of intestinal flora. Fifty-two healthy male Sprague-Dawley rats were randomly divided into four groups (i.e., control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to produce the stress depression model. Rats in the XYS and fluoxetine groups received intragastric administration of XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. Stool specimens were sequenced using the 16S rDNA high-throughput method to detect the structure and changes in intestinal flora. There was no difference observed in alpha diversity among the groups. At the phylum level, XYS regulated the abundance of Bacteroidetes, Proteobacteria, Firmicutes, Chloroflexi, and Planctomycetes. At the genus level, XYS reduced the abundance of the Prevotellaceae_Ga6A1_group, Prevotellaceae_UCG-001, and Desulfovibrio. On the contrary, it increased the abundance of the Ruminococcaceae family to improve depression-like behavior. The mechanism involved in this process may be related to short-chain fatty acids, lipopolysaccharides, and intestinal inflammation.

Author(s) Details:

Hui-Zheng Zhu,
The First Affiliated Hospital, Jinan University, Guangzhou-510632, Guangdong, China, Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen-529030, China.

Yu-Dan Liang,
Integrated Chinese and Western Medicine Postdoctoral research station, Jinan University, Guangzhou-510632, China.

Qing-Yu Ma,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Wen-Zhi Hao,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Xiao-Juan Li,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Man-Si Wu,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Li-Juan Deng,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Yu-Ming Li,
Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen-529030, China.

Jiaxu Chen,

Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11267

Influence of Xiaoyaosan on Depressive-like Behaviors in Chronic Stress-depressed Rats through Regulating Tryptophan Metabolism in Hippocampus | Chapter 5 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

 Background: Tryptophan metabolism has always been considered to play a vital role in mental disorder diseases, and how traditional Chinese formula Xiaoyaosan regulates the tryptophan metabolism is a complement to the pathogenesis of depression. This study established a depression rat model by the chronic immobilization stress (CIS) method and observed the change in tryptophan metabolism in hippocampus and the effects of Xiaoyaosan.

Methods: Forty-eight male Sprague Dawley (SD) rats were randomly divided into the following four groups: control group, CIS group, Xiaoyaosan group, and fluoxetine group. The depression model was established by the 21-day CIS. The food intake and body weight were recorded, and the sucrose preference test (SPT), novelty suppressed feeding (NSF) test and open field test (OFT) were also used to evaluate the model. Then, the contents of tryptophan and 5-hydroxytryptamine (5-HT) in hippocampus were detected by the ELISA method, and the expression levels of tryptophan hydrogenase 2 (TPH2) and indoleamine 2,3-dioxygenase 1 (IDO1) in hippocampus were determined by quantitative reverse transcriptase polymerase chain reaction reaction (qRT-PCR) and Western blot methods.

Results: The behavioral data showed a significant difference between the model group and the normal group. The 5-HT content in the hippocampi of CIS rats was significantly reduced, whereas the tryptophan content in the hippocampi of model rats was significantly increased. The TPH2 level in hippocampus of the model group was significantly decreased, and the IDO1 level was significantly increased. Xiaoyaosan and fluoxetine could significantly reverse these changes and had obvious curative effects.

Conclusion: The abnormal tryptophan metabolism existed in the hippocampi of chronic stress-depressed rats, which was closely related to the pathogenesis of depression. Xiaoyaosan could improve the tryptophan metabolism by regulating the expression levels of TPH2 and IDO1, thus exerting an antidepressant-like effect.

Author(s) Details:

Haiyan Jiao,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Zhiyi Yan,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Qingyu Ma,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Xiaojuan Li,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Youming Jiang,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Yueyun Liu,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Jiaxu Chen,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11266

Effect of Xiaoyaosan on Colon Morphology and Intestinal Permeability in Rats with Chronic Unpredictable Mild Stress | Chapter 2 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

 Purpose: In our present study, a rat depression model induced by 6 weeks of chronic unpredictable mild stress (CUMS) was established, and we investigated how Xiaoyaosan affects the intestinal permeability of depressed rats and alterations in tight-junction proteins (TJs) involved in this process.

Methods: The rat depression model was established using CUMS for 6 consecutive weeks. A total of 40 healthy male Sprague-Dawley rats were randomly sorted into four groups: the control group, CUMS group, Xiaoyaosan group, and fluoxetine group. All groups, excluding the control group, were subjected to the 6-week CUMS program to generate the depression model. Body weight, food intake, and behaviors were observed during the modeling period. Histopathological alterations of colon tissue were evaluated by hematoxylin-eosin staining (H&E), and mucus-containing goblet cells were detected by periodic acid-Schiff (PAS) staining. The ultrastructural morphology of colonic mucosa  was observed by transmission electron microscopy. Furthermore, immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to determine the expression of TJs. The concentrations of 5-hydroxytryptamine (5-HT) in the hypothalamus and colon were also assessed using enzyme-linked immunosorbent assay (ELISA).

Results: Treatment of depressed rats with Xiaoyaosan alleviated depression-like behaviors as demonstrated by increases in the total distance traveled, the number of entries into the central area in the open field test, the duration spent in the central area, and sucrose preference. Xiaoyaosan treatment also increased body weight gain and food intake in depressed rats. Moreover, Xiaoyaosan treatment effectively improved the colonic pathological and ultrastructural changes, upregulated the expression of ZO-1, occludin, and claudin-1 in the colon, and increased 5-HT levels in the hypothalamus and colonic mucosa.

Conclusions: Xiaoyaosan treatment attenuates depression-like behaviors caused by CUMS and ameliorates CUMS-induced abnormal intestinal permeability, which may be associated with the expression of TJs. These results suggest that Xiaoyaosan exerts an antidepressant effect that may be related to an improvement of intestinal barrier function via the brain-gut axis.

Author(s) Details:

Fengmin Ding,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Jiajia Wu,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Chenyue Liu,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Qinglai Bian,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Wenqi Qiu,
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Qingyu Ma,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Xiaojuan Li,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Man Long,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

 
Xiaojuan Zou,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

 
Jiaxu Chen,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11263

Effects of Xiaoyaosan on Depressive-Like Behaviors in Rats with Chronic Unpredictable Mild Stress through HPA Axis Induced Astrocytic Activities | Chapter 1 | Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan

 Astrocytes in the hippocampus are immediately relevant to depressive-like behavior. By regulating their activities, Xiaoyaosan (XYS), a traditional Chinese medicine compound, works in the treatment of depression.

Objective: Chronic unpredictable mild stress (CUMS) rat model was established to observe the regulation of XYS. We investigated the behavioral changes of CUMS, the expression of corticosterone (CORT) of the hypothalamo–pituitary–adrenal (HPA) axis, the expression of Glu-NMDA receptor and astrocytes glial fibrillary acidic protein (GFAP) in the hippocampus. We also investigated whether these changes were linked to XYS.

Methods: 80 adult SD rats were randomly divided into four groups, control group, CUMS group, XYS group, and fluoxetine group. The rats in the control group and the CUMS group received 0.5 ml of deionized water once a day by intragastrically administration. Rats in the two treatment groups received XYS (2.224g/kg/d) and fluoxetine (2.0mg/kg/d) once a day, respectively. Rat hippocampus GFAP and Glu-NMDA receptor were respectively detected by real-time fluorescent quantitative PCR and western blot. The CORT of HPA axis was detected by Elisa. Body weight, food intake, and behavioral tests, such as open field tests, the sucrose preference test, and exhaustive swimming test, were used to assess depressive-like behavior in rats.

Results: In this work, significant behavioral changes and differences in expression of the CORT of HPA axis and hippocampal GFAP and Glu-NMDA receptor were presented in CUMS-exposed rats. Like fluoxetine, XYS improved CUMS-induced rat’s body weight, food intake, and depressive-like behavior. The study also proved that XYS could reverse the CUMS-induced changes of the CORT of HPA axis and affect the astrocytic activities and down-regulate the NR2B subunit of NMDA receptor (NR2B) level in the hippocampus.

Conclusion: Changes in the hippocampus GFAP and Glu-NMDA receptor may be an essential mechanism of depression. Besides, XYS may be critical to the treatment of depression by intervention the HPA axis, GFAP and Glu-NMDA receptor.

Author(s) Details:

Ming Song,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Jianjun Zhang,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Xiaojuan Li,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Yueyun Liu,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Tingye Wang,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Zhiyi Yan,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China.

Jiaxu Chen,
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11262

Insights into the Prevention and Treatment of Depression with Famous TCM Prescription Xiaoyaosan | Book Publisher International

 Traditional Chinese medicine (TCM) prescription is a formula established based on clinical disease pattern differentiation, following the therapeutic principles and methods of TCM, in accordance with the compatibility rules of TCM as "Principals, associates, adjuvants and messengers". As the main method of TCM to treat diseases, TCM prescription is also the main embodiment of the philosophical speculation of TCM pattern differentiation and treatment. The elaboration of the mechanism of action and the material basis of traditional Chinese medicine prescription is of great significance to understanding disease pathogenesis and the revelation of therapeutic targets, embodying the scientific connotation of TCM. Xiaoyaosan (XYS) comes from the "Taiping Huimin Heji Bureau Prescription" in the Song Dynasty. As a representative prescription of TCM for the treatment of emotional diseases attributed to the pattern of liver depression and spleen deficiency, such as depression and anxiety, it has been used for thousands of years and has significant antidepressant and anti-anxiety effects.

Revealing the antidepressant and anti-anxiety pharmacodynamic mechanism of XYS and elaborating the material basis of XYS are of great significance for the research and treatment of emotional disorders and the elaboration of the scientific connotation of the correlation between Classical Prescription and pattern in TCM. By establishing three different depression models, including chronic unpredictable mild stress, chronic immobilized stress, and chronic restraint stress, combined with clinical research, network pharmacological analysis, ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS), 16S rDNA high-throughput method and molecular biology, we have revealed the antidepressant and anxiolytic mechanism of XYS and the material basis of its pharmacodynamics from multiple levels.

Our results show that XYS could target the central nervous system (CNS), liver, and intestinal tract to exert its medicinal effect. In the CNS, XYS has been shown to interfere with the hypothalamo-pituitary-adrena axis, glial fibrillary acidic protein and Glu-NMDA receptors; regulate the expression levels of tryptophan hydrogenase 2 and indoleamine 2,3-dioxygenase 1 in the hippocampus; regulate the glutamate/glutamine cycle and the glutamate transporter GLT-1 in the hippocampus; downregulate tumour necrosis factor-α/janus kinase 2-signal transducer and activator of transcription pathway in hippocampus; improve the function of astrocytes and excitatory amino acid transporters in prefrontal cortex; regulate nesfatin-1-oxytocin-proopiomelanocortin neural pathway in hypothalamus; regulate mRNA expression of related anabolic enzymes in hippocampus and amygdala, for antidepressant/anti-anxiety effects. In the periphery, XYS has been revealed to improve the abnormal levels of insulin, blood glucose, cholesterol, low-density lipoprotein and high-density lipoprotein in plasma by regulating the expression of SHIP2 in the liver. In the intestinal tract, XYS has been found to treat mood disorders by regulating the abundance of intestinal flora and reducing intestinal permeability. The joint analysis of network pharmacological analysis and UPLC-Q/TOF-MS showed that paeoniflorin, quercetin, luteolin, acacetin, aloe-emodin, Glyasperin C, kaempferol in XYS could play an antidepressant effect by regulating the pathways related to metabolism, neuroendocrine function and neuroimmunity, and affecting the expression of AKT1, TP53 and VEGFA genes.

In summary, we have collected into this book the representative studies published by Prof. Chen’s laboratory in 2020 and before. These studies reveal the pharmacodynamic mechanism of XYS for anti-depression and anti-anxiety, as well as clarify the material basis of XYS, which could serve as a practical reference value for researching and treating stress-related emotional disorders.

Author(s) Details:

Jiaxu Chen,

Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou-510632, Guangdong, China and School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing-100029, China.

Please see the link here: https://stm.bookpi.org/IPTDFTPX/article/view/11261