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

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

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

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