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Article ; Online: Kai-xin-san improves cognitive impairment in D-gal and Aβ

Wang, Huijuan / Zhou, Lifen / Zheng, Qin / Song, Yonggui / Huang, Weihua / Yang, Lin / Xiong, Yongchang / Cai, Zhinan / Chen, Ying / Yuan, Jinbin

Journal of ethnopharmacology

2024 Volume 329, Page(s) 118161

Abstract: Ethnopharmacological relevance: Kai-Xin-San (KXS) is a classic herbal formula for the treatment ...

Abstract	Ethnopharmacological relevance: Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood. Aim of the study: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota. Materials and methods: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aβ Results: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant. Conclusion: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.
Language	English
Publishing date	2024-04-09
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.2024.118161
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Article ; Online: Kai-Xin-San ameliorates Alzheimer's disease-related neuropathology and cognitive impairment in APP/PS1 mice via the mitochondrial autophagy-NLRP3 inflammasome pathway.

Shan, Xiaoxiao / Tao, Wenwen / Li, Junying / Tao, Wenkang / Li, Dawei / Zhou, Lele / Yang, Xuan / Dong, Chong / Huang, Shunwang / Chu, Xiaoqin / Zhang, Caiyun

Journal of ethnopharmacology

2024 Volume 329, Page(s) 118145

Abstract: Ethnopharmacological relevance: Kai-Xin-San (KXS) is a classic famous prescription that has been ...

Abstract	Ethnopharmacological relevance: Kai-Xin-San (KXS) is a classic famous prescription that has been utilized for centuries to address dementia. New investigations have shown that the anti-dementia effect of KXS is connected with improved neuroinflammation. Nevertheless, the underlying mechanism is not well elucidated. Aim of the study: We propose to discover the ameliorative impact of KXS on Alzheimer's disease (AD) and its regulatory role on the mitochondrial autophagy-nod-like receptor protein 3 (NLRP3) inflammasome pathway. Materials and methods: The Y maze, Morris water maze, and new objection recognition tests were applied to ascertain the spatial learning and memory capacities of amyloid precursor protein/presenilin 1 (APP/PS1) mice after KXS-treatment. Meanwhile, the biochemical indexes of the hippocampus were detected by reagent kits. The pathological alterations and mitochondrial autophagy in the mice' hippocampus were detected utilizing hematoxylin and eosin (H&E), immunohistochemistry, immunofluorescence staining, and transmission electron microscopy. Besides, the PTEN-induced putative kinase 1 (PINK1)/Parkin and NLRP3 inflammasome pathways protein expressions were determined employing the immunoblot analysis. Results: The results of behavioral tests showed that KXS significantly enhanced the AD mice' spatial learning and memory capacities. Furthermore, KXS reversed the biochemical index levels and reduced amyloid-β protein deposition in AD mice brains. Besides, H&E staining showed that KXS remarkably ameliorated the neuronal damage in AD mice. Concurrently, the results of transmission electron microscopy suggest that KXS ameliorated the mitochondrial damage in microglia and promoted mitochondrial autophagy. Moreover, the immunofluorescence outcomes exhibited that KXS promoted the expression of protein 1 light chain 3B (LC3B) associated with microtubule and the generation of autophagic flux. Notably, the immunofluorescence co-localization results confirmed the presence of mitochondrial autophagy in microglia. Finally, KXS promoted the protein expressions of the PINK1/Parkin pathway and reduced the activation of NLRP3 inflammasome. Most importantly, these beneficial effects of KXS were attenuated by the mitochondrial autophagy inhibitor chloroquine. Conclusion: KXS ameliorates AD-related neuropathology and cognitive impairment in APP/PS1 mice by enhancing the mitochondrial autophagy and suppressing the NLRP3 inflammasome pathway.
Language	English
Publishing date	2024-04-04
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.2024.118145
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Article ; Online: Classic Famous Prescription Kai-Xin-San Ameliorates Alzheimer's Disease via the Wnt/β-Catenin Signaling Pathway.

Shan, Xiaoxiao / Lv, Shujie / Huang, Peng / Zhang, Wei / Jin, Chuanshan / Liu, Yuanxu / Li, Yangyang / Jia, Yong / Chu, Xiaoqin / Peng, Can / Zhang, Caiyun

Molecular neurobiology

2023 Volume 61, Issue 4, Page(s) 2297–2312

Abstract: Kai-Xin-San (KXS) is a classic famous prescription composed of Polygalae Radix, Ginseng Radix et ...

Abstract	Kai-Xin-San (KXS) is a classic famous prescription composed of Polygalae Radix, Ginseng Radix et Rhizoma, Acori Tatarinowii Rhizoma, and Poria. Clinically, KXS is effective in treating amnesia and regulating cognitive dysfunction of Alzheimer's disease (AD), whereas its mechanism of action is still unclear. In this study, the AD model rats were established by combining intraperitoneal injection of D-galactose (150 mg/kg/day) and intracerebral injection of Aβ
MeSH term(s)	Rats ; Animals ; Alzheimer Disease/metabolism ; Caspase 3/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; beta Catenin/metabolism ; Wnt Signaling Pathway ; bcl-2-Associated X Protein ; Disease Models, Animal ; Drugs, Chinese Herbal
Chemical Substances	Kai-Xin-San ; Caspase 3 (EC 3.4.22.-) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; beta Catenin ; bcl-2-Associated X Protein ; Drugs, Chinese Herbal
Language	English
Publishing date	2023-10-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03707-y
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Article: Qing-Kai-Ling oral liquid alleviated pneumonia via regulation of intestinal flora and metabolites in rats.

Chen, Hongying / Li, Siju / Pan, Biyan / Liu, Kun / Yu, Hansheng / Ma, Chong / Qi, Huiyuan / Zhang, Yuefeng / Huang, Xinyi / Ouyang, Dongsheng / Xie, Zhiyong

Frontiers in microbiology

2023 Volume 14, Page(s) 1194401

Abstract: Background: Qing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known ... as An-Gong-Niu-Huang pills, is a well-established treatment for pneumonia with its mechanism remaining ...

Abstract	Background: Qing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known as An-Gong-Niu-Huang pills, is a well-established treatment for pneumonia with its mechanism remaining muddled. Studies have shown that the regulation of both intestinal flora and host-microbiota co-metabolism may contribute to preventing and treating pneumonia. The study aimed to investigate the potential mechanism by which QKL alleviates pneumonia from the perspective of 'microbiota-metabolites-host' interaction. Methods: We evaluated the therapeutic effects of QKL on lipopolysaccharide (LPS)-induced pneumonia rats. To explore the protective mechanism of QKL treatment, a multi-omics analysis that included 16S rDNA sequencing for disclosing the key intestinal flora, the fecal metabolome to discover the differential metabolites, and whole transcriptome sequencing of lung tissue to obtain the differentially expressed genes was carried out. Then, a Spearman correlation was employed to investigate the association between the intestinal flora, the fecal metabolome and inflammation-related indices. Results: The study demonstrated that pneumonia symptoms were significantly attenuated in QKL-treated rats, including decreased TNF-α, NO levels and increased SOD level. Furthermore, QKL was effective in alleviating pneumonia and provided protection equivalent to that of the positive drug dexamethasone. Compared with the Model group, QKL treatment significantly increased the richness and αlpha diversity of intestinal flora, and restored multiple intestinal genera (e.g., Conclusion: Our findings indicated that QKL could potentially modulate intestinal flora dysbiosis, improve host-microbiota co-metabolism dysregulation and regulate gene expression in the lungs, thereby mitigating LPS-induced pneumonia in rats. The study may provide new ideas for the clinical application and further development of QKL.
Language	English
Publishing date	2023-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1194401
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Article: Kai-Xin-San, a Chinese Herbal Decoction, Accelerates the Degradation of

Wang, Na / Jia, Yongming / Zhang, Bo / Li, Yan / Murtaza, Ghulam / Huang, Shuming / Liu, Xuewei

Evidence-based complementary and alternative medicine : eCAM

2020 Volume 2020, Page(s) 3862342

Abstract: This study aimed to investigate the mechanisms of Kai-Xin-San (KXS, a famous Chinese herbal ...

Abstract	This study aimed to investigate the mechanisms of Kai-Xin-San (KXS, a famous Chinese herbal decoction used to treat amnesia) on the degradation of A
Language	English
Publishing date	2020-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2020/3862342
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Zs.A 5995: Show issues

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Article ; Online: Neuroprotective mechanism of Kai Xin San

Na Wang / Yong-ming Jia / Bo Zhang / Di Xue / Maharjan Reeju / Yan Li / Shu-ming Huang / Xue-wei Liu

Neural Regeneration Research, Vol 12, Iss 4, Pp 654-

upregulation of hippocampal insulin-degrading enzyme protein expression and acceleration of amyloid-beta degradation

2017 Volume 659

Abstract: Kai Xin San is a Chinese herbal formula composed of Radix Ginseng , Poria , Radix Polygalae and ... Acorus Tatarinowii Rhizome . It has been used in China for many years for treating amnesia. Kai Xin San ... into the hippocampus and subsequently administered Kai Xin San (0.54 or 1.08 g/kg/d) intragastrically for 21 ...

Abstract	Kai Xin San is a Chinese herbal formula composed of Radix Ginseng , Poria , Radix Polygalae and Acorus Tatarinowii Rhizome . It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-β (Aβ)-induced cognitive dysfunction and is neuroprotective in vivo , but its precise mechanism remains unclear. Expression of insulin-degrading enzyme (IDE), which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ42 (200 μM, 5 μL) into the hippocampus and subsequently administered Kai Xin San (0.54 or 1.08 g/kg/d) intragastrically for 21 consecutive days. Hematoxylin-eosin and Nissl staining revealed that Kai Xin San protected neurons against Aβ-induced damage. Furthermore, enzyme-linked immunosorbent assay, western blot and polymerase chain reaction results showed that Kai Xin San decreased Aβ42 protein levels and increased expression of IDE protein, but not mRNA, in the hippocampus. Our findings reveal that Kai Xin San facilitates hippocampal Aβ degradation and increases IDE expression, which leads, at least in part, to the alleviation of hippocampal neuron injury in rats.
Keywords	nerve regeneration ; neurodegeneration ; traditional Chinese medicine ; Kai Xin San ; insulin-degrading enzyme ; amyloid-β ; Alzheimer′s disease ; Chinese herbal compound ; Aβ-degrading enzymes ; neurons ; Radix Ginseng ; Radix Polygalae ; Acorus Tatarinowii Rhizoma ; neural regeneration ; Neurology. Diseases of the nervous system ; RC346-429
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Traditional Formula Kai-Xin-San Alleviates Polyglutamine-Mediated Neurotoxicity by Modulating Proteostasis Network in

Xiao, Lingyun / Li, Haifeng / Tian, Jing / Jin, Nanxiang / Zhang, Ju / Yang, Fan / Zhou, Ling / Wang, Qiangqiang / Huang, Zebo

Rejuvenation research

2020 Volume 23, Issue 3, Page(s) 207–216

Abstract: The inherited polyglutamine (polyQ) expansion diseases are characterized by progressive accumulation of aggregation-prone polyQ proteins, which may provoke proteostasis imbalance and result in significant neurotoxicity. Using polyQ ... ...

Abstract	The inherited polyglutamine (polyQ) expansion diseases are characterized by progressive accumulation of aggregation-prone polyQ proteins, which may provoke proteostasis imbalance and result in significant neurotoxicity. Using polyQ transgenic
MeSH term(s)	Animals ; Animals, Genetically Modified ; Behavior, Animal/drug effects ; Caenorhabditis elegans ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Neurotoxicity Syndromes/metabolism ; Neurotoxicity Syndromes/pathology ; Neurotoxicity Syndromes/prevention & control ; Oxidative Stress/drug effects ; Peptides/toxicity ; Proteasome Endopeptidase Complex/drug effects ; Proteasome Endopeptidase Complex/metabolism ; Protein Aggregation, Pathological/metabolism ; Protein Aggregation, Pathological/prevention & control ; Proteome/drug effects ; Proteome/metabolism ; Proteostasis/drug effects
Chemical Substances	Drugs, Chinese Herbal ; Kai-Xin-San ; Peptides ; Proteome ; polyglutamine (26700-71-0) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2020-01-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2150779-X
ISSN	1557-8577 ; 1549-1684
ISSN (online)	1557-8577
ISSN	1549-1684
DOI	10.1089/rej.2018.2149
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Zs.A 5215: Show issues

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Article ; Online: Integrated meta-analysis, network pharmacology, and molecular docking to investigate the efficacy and potential pharmacological mechanism of Kai-Xin-San on Alzheimer's disease.

Yi, Pengji / Zhang, Zheyu / Huang, Siqi / Huang, Jiahua / Peng, Weijun / Yang, Jingjing

Pharmaceutical biology

2020 Volume 58, Issue 1, Page(s) 932–943

Abstract: Context: Kai-Xin-San (KXS) has been used to treat Alzheimer's disease (AD) for thousands of years ...

Abstract	Context: Kai-Xin-San (KXS) has been used to treat Alzheimer's disease (AD) for thousands of years. However, no quantitative data regarding AD treatment using KXS are available. Moreover, its active compounds and mechanism of action for the treatment of AD remain largely unclear. Objectives: To evaluate the efficacy and the potential pharmacological mechanisms of KXS in AD treatment. Materials and methods: A systematic collection of KXS experiments was conducted from PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang Data up to February, 2020. Review Manager 5 software was used for meta-analysis. In network pharmacology, components of KXS were screened, AD-related genes were then identified and the 'component-target-pathway' network constructed. Molecular docking was finally employed for Results: Meta-analysis revealed that KXS improves the cognitive benefits in AD models by reducing the time of escape latency (SMD = -16.84) as well as increasing the number of cross-platform (SMD = 2.56) and proportion of time in the target quadrant (SMD = 7.52). Network pharmacology identified 25 KXS active compounds and 44 genes targets. DRD2, MAOA, ACHE, ADRA2A and CHRM2 were core target proteins. Besides, 22 potential pathways of KXS were identified, like cholinergic synapses, the cGMP/PKG pathway and calcium signalling. Molecular docking showed that stigmasterol, aposcopolamine and inermin can closely bind three targets (ACHE, ADRA2A and CHRM2). Discussion and conclusion: These findings suggest that KXS exerts effect on AD through multi-target, multi-component and multi-pathway mechanism. Future studies may explore the active components of KXS.
MeSH term(s)	Alzheimer Disease/drug therapy ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Meta-Analysis ; Protein Interaction Maps ; Signal Transduction
Chemical Substances	Drugs, Chinese Herbal ; Kai-Xin-San
Language	English
Publishing date	2020-09-21
Publishing country	England
Document type	Journal Article ; Meta-Analysis
ZDB-ID	1440131-9
ISSN	1744-5116 ; 1388-0209
ISSN (online)	1744-5116
ISSN	1388-0209
DOI	10.1080/13880209.2020.1817103
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Zs.B 1300: Show issues

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Article: Chinese Medicine Formula Kai-Xin-San Ameliorates Neuronal Inflammation of CUMS-Induced Depression-like Mice and Reduces the Expressions of Inflammatory Factors via Inhibiting TLR4/IKK/NF-κB Pathways on BV2 Cells.

Qu, Suchen / Liu, Mengqiu / Cao, Cheng / Wei, Chongqi / Meng, Xue-Er / Lou, Qianyin / Wang, Bin / Li, Xuan / She, Yuyan / Wang, Qingqing / Song, Zhichao / Han, Zhengxiang / Zhu, Yue / Huang, Fei / Duan, Jin-Ao

Frontiers in pharmacology

2021 Volume 12, Page(s) 626949

Abstract: Kai-Xin-San (KXS) is a traditional Chinese medicinal formula composed of Ginseng Radix et Rhizoma ...

Abstract	Kai-Xin-San (KXS) is a traditional Chinese medicinal formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria for relieving major depressive disorder and Alzheimer's disease in traditional Chinese medicine (TCM) clinics. Previous studies on the antidepressant mechanism of KXS mainly focused on neurotransmitter and neurotrophic factor regulation, but few reports exist on neuronal inflammation regulation. In the current study, we found that KXS exerted antidepressant effects in chronic unpredictable mild stress-induced depression-like mice according to the results of behavioral tests. Meanwhile, KXS also inhibited the activation of microglia and significantly reduced the expression of pro-inflammatory cytokines such as IL-1β, IL-2, and TNF-α in the hippocampus of mice. In mice BV2 microglia cell lines, KXS extract reduced the expression of inflammatory factors in BV2 cells induced by lipopolysaccharide via inhibiting TLR4/IKK/NF-κB pathways, which was also validated by the treatment of signaling pathway inhibitors such as TAK-242 and JSH-23. T0hese data implied that the regulation of pro-inflammatory cytokines in microglia might account for the antidepressant effect of KXS, thereby providing more scientific information for the development of KXS as an alternative therapy for major depressive disorder.
Language	English
Publishing date	2021-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.626949
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Article ; Online: Kai-Xin-San, a Chinese Herbal Decoction, Accelerates the Degradation of β-Amyloid by Enhancing the Expression of Neprilysin in Rats

Na Wang / Yongming Jia / Bo Zhang / Yan Li / Ghulam Murtaza / Shuming Huang / Xuewei Liu

Evidence-Based Complementary and Alternative Medicine, Vol

2020 Volume 2020

Abstract: This study aimed to investigate the mechanisms of Kai-Xin-San (KXS, a famous Chinese herbal ...

Abstract	This study aimed to investigate the mechanisms of Kai-Xin-San (KXS, a famous Chinese herbal decoction used to treat amnesia) on the degradation of Aβ and further elucidate the mechanism of KXS on Aβ-induced memory dysfunction. After pretreatment with KXS (1.08 g/kg/day) for two weeks, Aβ42 (2 μL, 200 μM) was injected into rat hippocampus to induce cognitive dysfunction. Morris water maze (MWM) test was developed to evaluate cognitive performance in rats. Hippocampal neurons were observed by histological staining using Hematoxylin-Eosin (HE) methods. Levels of exogenous Aβ42, which was injected into the hippocampus, were continually measured through a special Enzyme-linked immunoassay (ELISA) kit to observe the catabolic process of Aβ in the brain. Similarly, Aβ degradation in PC12 cells was also investigated using the ELISA kit. The expressions of Aβ degeneration enzymes, including neprilysin (NEP), angiotensin-converting enzyme (ACE), and endothelin-converting enzyme (ECE), were detected by western blotting to elucidate Aβ reduction mechanism. Our results showed that KXS prevented Aβ42-induced cognitive impairment and attenuated hippocampus neuronal damage caused by Aβ42. Moreover, KXS could accelerate Aβ42 degradation in Aβ42 injected rats. Furthermore, NEP, an Aβ degradation enzyme, was increased in the hippocampus while ECE and ACE, other two Aβ-degrading enzymes, were not changed. KXS accelerated Aβ degradation in PC12 cells. Our findings revealed that KXS facilitated the degradation of Aβ42 by increasing the expression of NEP in rat hippocampus. By reducing the Aβ burdens, KXS protected hippocampal neurons, leading to the improvement of cognitive function in rats.
Keywords	Other systems of medicine ; RZ201-999
Subject code	616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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