Kaixinsan, a Well-Known Chinese Herbal Prescription, for Alzheimer's Disease and Depression: A Preclinical Systematic Review

Fu, Huan; Xu, Zhen; Zhang, Xile; Zheng, Guo-Qing

doi:10.3389/fnins.2019.01421

Cited by 30 publications

(23 citation statements)

References 75 publications

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“…Meyer, Poria cocos (Schw.) Wolf, Polygala tenuifolia Willd, and Acorus tatarinowii Schott [ 203 ]. A chronic administration of KXS (338 or 676 mg/kg, 3 weeks, i.g.)…”

Section: Chm Effects On the Neuroendocrine-immune Networkmentioning

confidence: 99%

Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network

Huang

Zhang

2021

Pharmaceuticals

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The neuroimmune and neuroendocrine systems are two critical biological systems in the pathogenesis of depression. Clinical and preclinical studies have demonstrated that the activation of the neuroinflammatory response of the immune system and hyperactivity of the hypothalamus–pituitary–adrenal (HPA) axis of the neuroendocrine system commonly coexist in patients with depression and that these two systems bidirectionally regulate one another through neural, immunological, and humoral intersystem interactions. The neuroendocrine-immune network poses difficulties associated with the development of antidepressant agents directed toward these biological systems for the effective treatment of depression. On the other hand, multidrug and multitarget Chinese Herbal Medicine (CHM) has great potential to assist in the development of novel medications for the systematic pharmacotherapy of depression. In this narrative essay, we conclusively analyze the mechanisms of action of CHM antidepressant constituents and formulas, specifically through the modulation of the neuroendocrine-immune network, by reviewing recent preclinical studies conducted using depressive animal models. Some CHM herbal constituents and formulas are highlighted as examples, and their mechanisms of action at both the molecular and systems levels are discussed. Furthermore, we discuss the crosstalk of these two biological systems and the systems pharmacology approach for understanding the system-wide mechanism of action of CHM on the neuroendocrine-immune network in depression treatment. The holistic, multidrug, and multitarget nature of CHM represents an excellent example of systems medicine in the effective treatment of depression.

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“…Meyer, Poria cocos (Schw.) Wolf, Polygala tenuifolia Willd, and Acorus tatarinowii Schott [ 203 ]. A chronic administration of KXS (338 or 676 mg/kg, 3 weeks, i.g.)…”

Section: Chm Effects On the Neuroendocrine-immune Networkmentioning

confidence: 99%

Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network

Huang

Zhang

2021

Pharmaceuticals

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“…For understanding the mechanism of action of a TCM formula at the systems level, it is essential to integrate the molecular mechanism into the system-wide mechanism of action. The representative TCM formulas in depression treatment are, but no limited to, Xiao-Yao-San (Chen et al, 2008), Kai-Xin-San (Fu et al, 2020), Jie-Yu-Wan (Feng et al, 2018), Shu-Yu-San (Chen et al, 2012), Chaihu-Jia-Longgu-Muli-Tang (Li et al, 2011), and so on. CUMS, chronic unpredictable mild stress; CSDS, chronic social defeat stress; CMS, chronic mild stress; SDM, social defeat model; CORT, corticosterone; CUS, chronic unpredictable stress; WKT, Wistar Kyoto; LPS, lipopolysaccharides.…”

Section: The Hpa Axismentioning

confidence: 99%

Traditional Chinese Medicine in Depression Treatment: From Molecules to Systems

Huang

Cheng

et al. 2020

Front. Pharmacol.

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Depression is a multigenetic or multifactorial syndrome. The central neuron system (CNS)orientated, single target, and conventional antidepressants are insufficient and far from ideal. Traditional Chinese Medicine (TCM) has historically been used to treat depression up till today, particularly in Asia. Its holistic, multidrug, multitarget nature fits well with the therapeutic idea of systems medicine in depression treatment. Over the past two decades, although efforts have been made to understand TCM herbal antidepressants at the molecular level, many fundamental questions regarding their mechanisms of action remain to be addressed at the systems level in order to better understand the complicated herbal formulations in depression treatment. In this Mini Review, we review and discuss the mechanisms of action of herbal antidepressants and their acting targets in the pathological systems in the brain, such as monoamine neurotransmissions, hypothalamic-pituitary-adrenal (HPA) axis, neurotropic factor brain-derived neurotrophic factor (BDNF) cascade, and glutamate transmission. Some herbal molecules, constituents, and formulas are highlighted as examples to discuss their mechanisms of action and future directions for comprehensive researches at the systems level. Furthermore, we discuss pharmacological approaches to integrate the mechanism of action from the molecular level into the systems level for understanding of systems pharmacology of TCM formulations. Integration of the studies at the molecular level into the systems level not only represents a trend in TCM study but also promotes our understanding of the system-wide mechanism of action of herbal antidepressant formulations.

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“…Wolf (PO), and Acorus tatarinowii Schott (AT) [ 19 ]. As a classic formula, KXS has been applied in amnesia treatment for thousands of years [ 20 ] and displays profound therapeutic effect for dementia and depression in clinical trials[ 21 ]. Some researchers have found that KXS exerts cardioprotective effects in a myocardial infarction [ 22 ], and could ameliorate chronic fatigue syndrome by affecting the levels of inflammatory factors [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Kai-Xin-San Inhibits Tau Pathology and Neuronal Apoptosis in Aged SAMP8 Mice

et al. 2022

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Alzheimer’s disease (AD) is an age-related neurological disorder. Currently, there is no effective cure for AD due to its complexity in pathogenesis. In light of the complex pathogenesis of AD, the traditional Chinese medicine (TCM) formula Kai-Xin-San (KXS), which was used for amnesia treatment, has been proved to improve cognitive function in AD animal models. However, the active ingredients and the mechanism of KXS have not yet been clearly elucidated. In this study, network pharmacology analysis predicts that KXS yields 168 candidate compounds acting on 863 potential targets, 30 of which are associated with AD. Enrichment analysis revealed that the therapeutic mechanisms of KXS for AD are associated with the inhibition of Tau protein hyperphosphorylation, inflammation, and apoptosis. Therefore, we chose 7-month-old senescence-accelerated mouse prone 8 (SAMP8) mice as AD mouse model, which harbors the behavioral and pathological hallmarks of AD. Subsequently, the potential underlying action mechanisms of KXS on AD predicted by the network pharmacology analyses were experimentally validated in SAMP8 mice after intragastric administration of KXS for 3 months. We observed that KXS upregulated AKT phosphorylation, suppressed GSK3β and CDK5 activation, and inhibited the TLR4/MyD88/NF-κB signaling pathway to attenuate Tau hyperphosphorylation and neuroinflammation, thus suppressing neuronal apoptosis and improving the cognitive impairment of aged SAMP8 mice. Taken together, our findings reveal a multi-component and multi-target therapeutic mechanism of KXS for attenuating the progression of AD, contributing to the future development of TCM modernization, including KXS, and broader clinical application. Graphical abstract

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Kaixinsan, a Well-Known Chinese Herbal Prescription, for Alzheimer's Disease and Depression: A Preclinical Systematic Review

Cited by 30 publications

References 75 publications

Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network

Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network

Traditional Chinese Medicine in Depression Treatment: From Molecules to Systems

Kai-Xin-San Inhibits Tau Pathology and Neuronal Apoptosis in Aged SAMP8 Mice

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