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Article: Corrigendum: Systems pharmacology approach to investigate the mechanism of Kai-Xin-San in Alzheimer's disease.

Luo, Yunxia / Li, Dongli / Liao, Yanfang / Cai, Chuipu / Wu, Qihui / Ke, Hanzhong / Liu, Xinning / Li, Huilin / Hong, Honghai / Xu, Yumin / Wang, Qi / Fang, Jiansong / Fang, Shuhuan

Frontiers in pharmacology

2023 Volume 14, Page(s) 1239060

Abstract: This corrects the article DOI: 10.3389/fphar.2020.00381.]. ...

Abstract	[This corrects the article DOI: 10.3389/fphar.2020.00381.].
Language	English
Publishing date	2023-10-06
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1239060
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The Use of San-Huang-Xie-Xin-Tang Reduces the Mortality Rate among Breast Cancer Patients.

Winardi, Daniel / Wu, Chieh-Hsin / Chiang, Jen-Huai / Chen, Yung-Hsiang / Hsieh, Ching-Liang / Yang, Juan-Cheng / Wu, Yang-Chang

Cancers

2023 Volume 15, Issue 4

Abstract: ... prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory ...

Abstract	Globally, breast cancer is the most common cause of cancer deaths. In Taiwan, it is the most prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory but an immunomodulatory effect, it may act as a potent anti-tumor agent. Herein, the study aimed to explore the influence of SHXXT and its constituents on the mortality rate among breast cancer patients in Taiwan regarding the component effect and the dose-relationship effect. By using the Taiwan National Health Insurance (NHI) Research Database (NHIRD), the study analyzed 5387 breast cancer patients taking Chinese herbal medicine (CHM) and 5387 breast cancer patients not using CHM. CHM means SHXXT and its constituents in the study. The Kaplan-Meier method was utilized to determine the mortality probabilities among patients. Whether the CHM influences the mortality rate among patients was estimated by Cox proportional hazard regression analysis. The use of CHM could lower the cancer mortality rate by 59% in breast cancer patients. The protective effect was parallel to the cumulative days of CHM use and the annual average CHM dose. In addition, the mortality rate was lower in patients who used SHXXT compared to those who only used one of its constituents. SHXXT and its constituents were all promising therapeutic weapons against breast cancer.
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15041213
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Article ; Online: Ban-xia-xie-xin-tang ameliorates hepatic steatosis by regulating Cidea and Cidec expression in HFD-fed mice.

Xia, Qing-Song / Gao, Yang / Wen-Bin, Wu / Wu, Fan / Dong, Hui / Xu, Li-Jun / Fang, Ke / Hu, Mei-Lin / Yuan, Fen / Lu, Fu-Er / Gong, Jing

Phytomedicine : international journal of phytotherapy and phytopharmacology

2022 Volume 105, Page(s) 154351

Abstract: Background: Ban-xia-xie-xin-tang (BXXXT) has been applied in treating metabolic diseases ...

Abstract	Background: Ban-xia-xie-xin-tang (BXXXT) has been applied in treating metabolic diseases, such as nonalcohol fatty liver disease, diabetes mellitus, and obesity. However, the underlying molecular mechanism of BXXXT in treating diabetes mellitus is unknown. Purpose: To clarify the underlying molecular mechanism of BXXXT in alleviating hepatic steatosis in high-fat diet (HFD)-fed mice. Methods: After 12 weeks of HFD treatment, mice were administered BXXXT for 4 weeks. The main chemical components of BXXXT were identified by UPLC-TQ-MS/MS. Indicators associated with insulin resistance and lipid metabolism were detected. The effect of improving glucose and lipid metabolism between BXXXT and the different components was compared. Differentially expressed genes (DEGs) were identified by hepatic transcriptomics. Key DEGs and proteins were further detected by real-time quantitative polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence staining. LDs and mitochondria were detected by transmission electron microscopy. Results: First of all, our data demonstrated that the capacity to improve glucose and lipid metabolism for BXXXT was significantly superior to different components of BXXXT. BXXXT was found to improve HFD-induced insulin resistance. Moreover, BXXXT decreased weight, serum/hepatic triglycerides, total cholesterol, and FFAs to alleviate HFD-induced hepatic steatosis. According to the results of the hepatic transcription, Cidea and Cidec were identified as critical DEGs for promoting LD fusion and reducing FFAs β-oxidation in mitochondria and peroxisome resulting in hepatic steatosis, which was reversed by BXXXT. Conclusion: BXXXT ameliorates HFD-induced hepatic steatosis and insulin resistance by increasing Cidea and Cidec-mediated mitochondrial and peroxisomal fatty acid oxidation, which may provide a potential strategy for therapy of NAFLD and T2DM.
MeSH term(s)	Animals ; Apoptosis Regulatory Proteins ; Diet, High-Fat ; Fatty Acids, Nonesterified ; Glucose ; Insulin Resistance ; Liver ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease ; Pinellia ; Tandem Mass Spectrometry
Chemical Substances	Apoptosis Regulatory Proteins ; Cidea protein, mouse ; Fatty Acids, Nonesterified ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-07-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2022.154351
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Article ; Online: Wei-Tong-Xin ameliorates functional dyspepsia via inactivating TLR4/MyD88 by regulating gut microbial structure and metabolites.

Zhang, Xiaoying / Liu, Wenjuan / Zhang, Shuanglin / Wang, Jinyu / Yang, Xihan / Wang, Ruixuan / Yan, Tingxu / Wu, Bo / Du, Yiyang / Jia, Ying

Phytomedicine : international journal of phytotherapy and phytopharmacology

2022 Volume 102, Page(s) 154180

Abstract: Background: Wei-Tong-Xin (WTX) is a traditional Chinese medicine (TCM) that has been screened and ...

Abstract	Background: Wei-Tong-Xin (WTX) is a traditional Chinese medicine (TCM) that has been screened and improved in accordance with the famous ancient Chinese formula "Wan Ying Yuan". It has been shown to be clinically effective in treating gastric dysmotility, but its underlying molecular mechanism remains unclear. Purpose: This study primarily dealt with the effects and mechanisms of WTX on functional dyspepsia (FD) induced by chemotherapeutic drug cisplatin (CIS). Methods: Firstly, the UPLC fingerprint and multi-component determination of WTX were established. In vivo, gastrointestinal motility of mice was detected by charcoal propulsion test. Besides, H&E, western blot and qRT-PCR were performed to evaluate the occurrence of gastric antral inflammation. ROS-DHE staining was used to detect ROS levels. Further, the gut microbiota were subjected to sequencing by 16S rRNA, and the levels of bacterial metabolites short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS) were detected by GC-MS and Limulus kits, respectively. The levels of GLP-1 in gastric antrum were assessed by ELISA kits. Finally, siRNA-FFAR2 experiment was performed in Raw 264.7 cells. Results: 23 common peaks were obtained from the UPLC fingerprint, and the content of 10 target components was determined. WTX increased the relative abundance of Firmicutes and decreased the number of Verrucomicrobia, accompanied by changes in the levels of SCFAs and LPS. By mediating the expression changes of free fatty acid receptor 2 (FFAR2) and toll-like receptor 4 (TLR4), WTX inhibited the phosphorylation of nuclear factor-κB (NF-κB), JNK and P38, decreased the levels of IL-1β, inducible nitric oxide synthase (iNOS) and ROS, increased the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), IL-4 and arginase-1 (Arg-1). Decreased expressions of glucagon-like peptide 1 (GLP-1) induced by WTX promoted gastric motility in FD mice. In vitro, siRNA-FFAR2 of Raw 264.7 cells eliminated the effects of WTX on TLR4 signaling pathway. Conclusions: In this study, the chemical profile of WTX was first reported. Based on remodeling the gut microbiota structure and adjusting the levels of metabolites (SCFAs and LPS), WTX inactivated the TLR4/MyD88 signaling pathway to inhibit the occurrence of gastric antral inflammation, which reversed the inhibitory effect of GLP-1 on gastric motility, and improved CIS-induced FD symptoms.
MeSH term(s)	Animals ; Dyspepsia/drug therapy ; Dyspepsia/metabolism ; Dyspepsia/microbiology ; Gastrointestinal Microbiome ; Glucagon-Like Peptide 1 ; Inflammation/drug therapy ; Lipopolysaccharides/pharmacology ; Mice ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; RNA, Ribosomal, 16S ; RNA, Small Interfering ; Reactive Oxygen Species/metabolism ; Toll-Like Receptor 4/metabolism
Chemical Substances	Lipopolysaccharides ; Myd88 protein, mouse ; Myeloid Differentiation Factor 88 ; NF-kappa B ; RNA, Ribosomal, 16S ; RNA, Small Interfering ; Reactive Oxygen Species ; Tlr4 protein, mouse ; Toll-Like Receptor 4 ; Glucagon-Like Peptide 1 (89750-14-1)
Language	English
Publishing date	2022-05-18
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2022.154180
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Article ; Online: Uncovering the pharmacological mechanism of Wei-Tong-Xin against gastric ulcer based on network pharmacology combined with in vivo experiment validation.

Liu, Wenjuan / Zhang, Xiaoying / Ma, Tiancheng / Wang, Jinyu / Lv, Xinyan / Wu, Bo / Yan, Tingxu / Jia, Ying

Journal of ethnopharmacology

2022 Volume 293, Page(s) 115282

Abstract: Ethnopharmacological relevance: The prescription of Wei-Tong-Xin (WTX) is improved based ...

Abstract	Ethnopharmacological relevance: The prescription of Wei-Tong-Xin (WTX) is improved based on the prescription "Wanyingyuan", a famous decoction documented in the book of Huatuozhongzangjing in the Han dynasty. Many years of clinical verification have demonstrated that WTX can be used to treat gastrointestinal diseases, especially gastric ulcer (GU). However, the potential pharmacological mechanism is undefined. Aim of the study: This research was conducted to explore the pharmacological mechanisms under the consideration of the therapeutical effect of WTX against GU by combining the network pharmacology strategy and in-vivo verified experiments. Materials and methods: A prediction network describing the relationship between WTX and GU was established based on information collected from multiple databases. Then, the intersecting protein-protein interaction (PPI) network of the drug-disease overlapping gene targets was constructed, and several key targets related to both WTX and GU were obtained. Besides, the Gene Ontology (GO) biological enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the key target genes and pathways of WTX against GU. Then, the candidate targets and signaling pathways of network pharmacology were validated in a rat model of GU induced by indomethacin following the results and available proof. Results: There are 243 targets obtained from the 65 active ingredients in WTX, and 1362 disease targets related to GU were identified. Then, 6 key targets were determined with the PPI interaction network, which was structured from 126 overlapping gene targets. GO and KEGG analyses revealed that the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signaling pathway might play a crucial role in the therapeutic mechanism of GU. In vivo verified experiments, WTX significantly reduced the ulcer area and improved the histopathological appearance of gastric tissues. Moreover, down-regulated the protein levels of IL6, TNF-α, and Caspase 3 in the gastric tissues while up-regulating the expression of p-PI3K, p-AKT, p-P53, and VEGFA compared to the model group. Conclusion: WTX, an ancient traditional Chinese medicine (TCM) compound prescription, may affect the inflammatory response and apoptosis process by regulating PI3K/AKT signaling pathway and related gene targets. Therefore, it is an effective drug candidate for the modern treatment of GU.
MeSH term(s)	Animals ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Network Pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Stomach Ulcer/chemically induced ; Stomach Ulcer/drug therapy
Chemical Substances	Drugs, Chinese Herbal ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2022-04-09
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2022.115282
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Article ; Online: Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of Deng-Zhan-Xi-Xin injection in the treatment of ischemic stroke.

Zhao, Jing / Lv, Chao / Wu, Qiuling / Zeng, Huawu / Guo, Xin / Yang, Jian / Tian, Saisai / Zhang, Weidong

Pharmacological research

2019 Volume 147, Page(s) 104365

Abstract: ... by drugs on human signaling networks. To establish proof of principle, the herbal product Deng-Zhan-Xi-Xin ...

Abstract	Herbs are typically prescribed in traditional Chinese medicine (TCM) to treat complex diseases. The multicomponent nature of herbal drug ingredients makes it difficult to readily understand their mode of action. To decipher their molecular mechanisms, here we proposed a novel computational systems pharmacology based approach, which consisted of transcriptome profiling, data collection, statistical analysis, network algorithm, bioinformatics analysis and pharmacological validation. The network algorithm called signed random walk with restart (SRWR) was used to simulate the propagation of drugs' effects on networks. This algorithm could identify proteins either positively or negatively regulated (activated or inhibited) by drugs on human signaling networks. To establish proof of principle, the herbal product Deng-Zhan-Xi-Xin injection (DZXXI), which exhibits pharmacological effects in ischemic stroke but its mechanism was unclear, was analyzed. Eighty-three targets were predicted with high confidence for DZXXI's active compounds in plasma, and 87 differentially expressed genes (DEGs) were identified in MCF7 cells treated with DZXXI. These target genes were further found to be associated with pathways involved in neuronal apoptosis in ischemic stroke, such as NF-κB signaling, TNF signaling, and PI3K-Akt signaling. Intersection analysis between DZXXI's putative targets with ischemic stroke-associated genes identified two important targets (PTGS1, PTGS2) corresponding to four DZXXI compounds, which were further validated using in silico and in vitro/vivo models. The most inhibited genes identified by the SRWR algorithm were significantly enriched with ischemic stroke-associated disease genes, antiplatelet associated pathways, and their encoded proteins were enriched in brain, vascular endothelium and platelets. The CMAP analysis based on DEGs suggested that DZXXI could function as both an anti-inflammatory and anti-platelet agent. Taken together, the computational analysis suggested that DZXXI exhibited anti-platelet and neuroprotective effects in the treatment of ischemic stroke. These deductions were preliminarily confirmed by subsequent in vitro/vivo studies. This approach provides a systems perspective to study the relevance between herbal drugs and disease processes, and can reveal possible pharmacological effects of multiple ingredients within herbal product.
MeSH term(s)	Animals ; Computational Biology ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Gene Expression Profiling ; Humans ; Infarction, Middle Cerebral Artery/drug therapy ; MCF-7 Cells ; Male ; Mice ; Molecular Docking Simulation ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; RAW 264.7 Cells ; Rabbits ; Rats, Sprague-Dawley ; Transcriptome/drug effects
Chemical Substances	Drugs, Chinese Herbal ; Neuroprotective Agents ; Platelet Aggregation Inhibitors
Language	English
Publishing date	2019-07-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2019.104365
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Article: Systems Pharmacology Approach to Investigate the Mechanism of Kai-Xin-San in Alzheimer's Disease.

Luo, Yunxia / Li, Dongli / Liao, Yanfang / Cai, Chuipu / Wu, Qihui / Ke, Hanzhong / Liu, Xinning / Li, Huilin / Hong, Honghai / Xu, Yumin / Wang, Qi / Fang, Jiansong / Fang, Shuhuan

Frontiers in pharmacology

2020 Volume 11, Page(s) 381

Abstract: ... dysfunction. Kai-Xin-San (KXS) is a traditional Chinese medicine (TCM) formula that has been used to treat AD ...

Abstract	Alzheimer's disease (AD) is a complex neurodegenerative disease characterized by cognitive dysfunction. Kai-Xin-San (KXS) is a traditional Chinese medicine (TCM) formula that has been used to treat AD patients for over a thousand years in China. However, the therapeutic mechanisms of KXS for treating AD have not been fully explored. Herein, we used a comprehensive network pharmacology approach to investigate the mechanism of action of KXS in the treatment of AD. This approach consists of construction of multiple networks and Gene Ontology enrichment and pathway analyses. Furthermore, animal experiments were performed to validate the predicted molecular mechanisms obtained from the systems pharmacology-based analysis. As a result, 50 chemicals in KXS and 39 AD-associated proteins were identified as major active compounds and targets, respectively. The therapeutic mechanisms of KXS in treating AD were primarily related to the regulation of four pathology modules, including amyloid beta metabolism, tau protein hyperphosphorylation process, cholinergic dysfunction, and inflammation. In scopolamine-induced cognitive dysfunction mice, we validated the anti-inflammatory effects of KXS on AD by determining the levels of inflammation cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. We also found cholinergic system dysfunction amelioration of KXS is correlated with upregulation of the cholinergic receptor CHRNB2. In conclusion, our work proposes a comprehensive systems pharmacology approach to explore the underlying therapeutic mechanism of KXS for the treatment of AD.
Language	English
Publishing date	2020-04-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.00381
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Article ; Online: Retraction Note to: External Qi of Yan Xin Qigong induces G2/M arrest and apoptosis of androgen-independent prostate cancer cells by inhibiting Akt and NF- B pathways.

Yan, Xin / Shen, Hua / Jiang, Hongjian / Zhang, Chengsheng / Hu, Dan / Wang, Jun / Wu, Xinqi

Molecular and cellular biochemistry

2021 Volume 476, Issue 6, Page(s) 2573

Language	English
Publishing date	2021-04-23
Publishing country	Netherlands
Document type	Retraction of Publication
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-021-04163-9
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Article ; Online: Yi-Xin-Shu capsule ameliorates cardiac hypertrophy by regulating RB/HDAC1/GATA4 signaling pathway based on proteomic and mass spectrometry image analysis.

Zhang, Minyu / Guo, Feifei / Li, Xianyu / Xian, Minghua / Wang, Tingting / Wu, Hongwei / Wei, Junying / Huang, Ying / Cui, Xiangning / Wu, Sha / Gong, Muxin / Yang, Hongjun

Phytomedicine : international journal of phytotherapy and phytopharmacology

2022 Volume 103, Page(s) 154185

Abstract: ... in CHF. Yi-Xin-Shu capsule (YXS) has been commonly applied in the clinical treatment of CHF in Asian ...

Abstract	Background: Cardiac hypertrophy (CH) forms the main pathological basis of chronic heart failure (CHF). Mitigating and preventing CH is the key strategy for the treatment of ventricular remodeling in CHF. Yi-Xin-Shu capsule (YXS) has been commonly applied in the clinical treatment of CHF in Asian countries for several decades. However, the underlying mechanism of YXS has not been revealed yet. Purpose: To assess the efficiency of YXS in CH and identify its potential therapeutic targets for the managing of CH. Method: Ultrasonic cardiogram was used to evaluate the cardiac function of CH rats. Hematein Eosin (HE)-staining, Masson-staining and transmission electron microscope were used to measure the morphological changes, cardiac fibrosis degree and ultrastructure characteristics of cardiomyocytes, respectively. ELISA was used to detect the myocardial injury biomarkers. Then, the potential targets regulated by YXS were screened out via proteomic analysis and mass spectrometry image analysis. Finally, the targets were validated by real-time quantitative (RT-q) PCR, immunofluorescence, immunohistochemistry, and western-blotting methods. Results: YXS improved the cardiac function of CH rats and attenuated the injuries in morphology and subcellular structure of cardiomyocytes. A core protein-protein interaction network was established on differentially expressed proteins (DEP) using proteomics analysis. GATA binding protein 4 (GATA4) was identified as the key target regulated by YXS. The results of mass spectrometry image analysis indicated that the expressions of histone deacetylase 1 (HDAC1) and retinoblastoma (RB) could also be regulated by YXS. Further valuative experiments showed that YXS may attenuate CH by regulating the RB/HDAC1/GATA4 signaling pathway. Conclusions: For the first time, this study discloses the precise mechanism investigation of the efficacy of YXS against CH. These data demonstrate that YXS may protect against CH by regulating the RB/HDAC1/GATA4 signaling pathway.
MeSH term(s)	Animals ; Cardiomegaly/drug therapy ; Cardiomegaly/metabolism ; Drugs, Chinese Herbal ; GATA4 Transcription Factor/metabolism ; Heart Failure/drug therapy ; Heart Failure/metabolism ; Histone Deacetylase 1/metabolism ; Mass Spectrometry ; Myocytes, Cardiac/metabolism ; Proteomics ; Rats ; Retinal Neoplasms/metabolism ; Retinoblastoma/metabolism ; Signal Transduction
Chemical Substances	Drugs, Chinese Herbal ; GATA4 Transcription Factor ; Gata4 protein, rat ; yi-xin-shu ; Hdac1 protein, rat (EC 3.5.1.98) ; Histone Deacetylase 1 (EC 3.5.1.98)
Language	English
Publishing date	2022-06-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2022.154185
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Article ; Online: Novel insights into antidepressant mechanism of Kai Xin San formula: Inhibiting NLRP3 inflammasome activation by promoting autophagy.

Yu, Shangmin / Liu, Shan / Wang, Ning / Yu, Di / Qin, Meng / Wu, Ji / Guan, Qingxiang

Phytomedicine : international journal of phytotherapy and phytopharmacology

2021 Volume 93, Page(s) 153792

Abstract: Background: Kai Xin San (KXS) was widely applied for the treatment of depression for thousands ...

Abstract	Background: Kai Xin San (KXS) was widely applied for the treatment of depression for thousands of years. However, the underlying antidepressant mechanism of KXS remains not clear. Purpose: This study aimed to investigate whether NLRP3 inflammasome and autophagy are involved in inflammation-induced depression and antidepressant mechanism of KXS. Methods: Wistar rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks, and KXS (3, 5, and 10 g/kg/d) was administrated during the last 2 weeks of CUMS procedure. The effects of KXS on depressive-like behaviors, neuroinflammation, NLRP3 inflammasome activation, and autophagy were investigated in CUMS rats. Rat astrocytes were employed to further explore the potential mechanism of KXS in regulating NLRP3 inflammasome and autophagy. Autophagy inhibitor 3-methyladenine (3-MA, 5 mM) was used in vitro to elucidate the role of autophagy in the antidepressant mechanism of KXS. Results: In vivo, KXS improved depressive-like behaviors of CUMS rats in sucrose preference test, open field test and forced swimming test. Moreover, KXS inhibited the neuroinflammation induced by CUMS and promoted autophagy in prefrontal cortex of rats. The results in vitro further validated the anti-inflammatory and proautohapgic effects of KXS. More importantly, autophagy inhibitor 3-MA diminished the inhibitory effect of KXS on NLRP3 inflammasome activation in rat astrocytes. Conclusion: KXS ameliorated CUMS-induced depressive behaviors in rats and inhibited the NLRP3 inflammasome-mediated inflammation in vivo and in vitro. These effects might be regulated by KXS-induced autophagy.
MeSH term(s)	Animals ; Antidepressive Agents/pharmacology ; Autophagy ; Disease Models, Animal ; Drugs, Chinese Herbal ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Rats, Wistar ; Stress, Psychological
Chemical Substances	Antidepressive Agents ; Drugs, Chinese Herbal ; Inflammasomes ; Kai-Xin-San ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, rat
Language	English
Publishing date	2021-10-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2021.153792
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