Chinese Medicine: A Hope for Neurodegenerative Diseases?

Law, Betty Yuen Kwan; Wu, An Guo; Wang, Min Jun; Zhu, Yi‐Zhun

doi:10.3233/jad-170374

Cited by 17 publications

(14 citation statements)

References 82 publications

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“…Traditional Chinese medicine (TCM), which embraces centuries of knowledge and practical experience, has been used to treat many complex diseases in China for over 2,000 years (Cooper and Ma, 2017;Jiang et al, 2017). TCM has advantages for multi-targeting in intervention and treatment and has provided comprehensive prospects for understanding physiopathology and drug development for neurodegenerative diseases, including AD (Ho et al, 2010;Law et al, 2017). Kai-Xin-San (KXS) is a widely used TCM formula initially recorded in Beiji Qianjin Yaofang for treating dementia and depression in China since the Tang Dynasty.…”

Section: Introductionmentioning

confidence: 99%

Systems Pharmacology Approach to Investigate the Mechanism of Kai-Xin-San in Alzheimer’s Disease

Luo

Liao

et al. 2020

Front. Pharmacol.

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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-1b, and tumor necrosis factor (TNF)-a. 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.

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Section: Introductionmentioning

confidence: 99%

Systems Pharmacology Approach to Investigate the Mechanism of Kai-Xin-San in Alzheimer’s Disease

Luo

Liao

et al. 2020

Front. Pharmacol.

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“…Parkinson's disease poses a grave threat to the health and life of the elderly, with limited therapies to alleviate clinical symptoms (Huang et al, 2020). Chinese traditional herbal has been applied in the management of senile diseases for a long time, and its pharmacological effects on improving the symptoms or intervening pathogenesis of neurodegenerative diseases have been recognized (Law et al, 2017). AS-IV extracted from Astragalus membranaceus has been proven to bear neuroprotective effects in animal models of neurodegenerative diseases (Zhao et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

Xu¹,

Yang²,

Huang³

et al. 2021

Front. Neurosci.

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ObjectivesAstragaloside IV (AS-IV), the main active component of Astragalus membranaceus, bears anti-inflammatory, antioxidant, and neuroprotective activity. Parkinson’s disease (PD) is a common neurodegenerative disease. This study explored the protective effect of AS-IV on the cell model of PD.Materials and MethodsSH-SY5Y cells were incubated with different concentrations (10, 50, 100, 150, and 200 μM) of 6-hydroxydopamine (6-OHDA) for 0, 3, 6, 12, 24, and 48 h to establish the PD cell model. Different concentrations (0, 25, 50, 100, 150, and 200 μM) of AS-IV or 15 mM JAK2/STAT3 pathway inhibitor SC99 was added for intervention 2 h before 6-OHDA treatment. The viability and morphological damage of 6-OHDA-treated SH-SY5Y cells were measured using MTT assay and Hoechst 33258 staining. The expression of microtubule associated protein 2 (MAP2) was detected by immunofluorescence staining. The levels of inflammation and oxidative stress were measured using ELISA. Apoptosis of 6-OHDA-treated SH-SY5Y cells was detected using flow cytometry, and phosphorylation level of JAK2 and STAT3 were detected using Western blot analysis.ResultsThe survival rate of SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h was about 50%. AS-IV (25–100 μM) significantly improved the viability (all p < 0.01), increased MAP2 expression, and repaired the morphological damage induced by 6-OHDA. AS-IV inhibited IL-1β, IL-6, and TNF-α level (all p < 0.05), reduced MDA and ROS content and increased SOD concentration, thereby reducing inflammation and oxidative stress (all p < 0.01) in 6-OHDA-treated SH-SY5Y cells. Moreover, AS-IV decreased apoptosis rate and Bax/Bcl-2 ratio induced by 6-OHDA (all p < 0.05). Mechanically, AS-IV significantly increased the phosphorylation of JAK2 and STAT3 (p < 0.01); the addition of SC99 decreased the cell viability, increased the apoptosis rate, enhanced the levels of inflammatory factors and oxidative stress.ConclusionAS-IV enhanced the cell viability, and inhibited apoptosis, inflammation and oxidative stress of 6-OHDA-treated SH-SY5Y cells via activating the JAK2/STAT3 signaling pathway. This study may confer novel insights for the management of PD.

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“…Another major limitation is the lack of safety and efficacy profile for the natural remedies and compounds studied in this review. It is not known whether the dosage of decoctions with complex formulations and compounds administered may lead to potential toxicity, adverse effects or will be present at the intended site of action in sufficient concentration [118][119][120]. This is also further complicated with the lack of understanding of the molecular targets and mechanism involving the natural remedies [120].…”

Section: Limitations and Future Prospectsmentioning

confidence: 99%

“…It is not known whether the dosage of decoctions with complex formulations and compounds administered may lead to potential toxicity, adverse effects or will be present at the intended site of action in sufficient concentration [118][119][120]. This is also further complicated with the lack of understanding of the molecular targets and mechanism involving the natural remedies [120]. Greater understanding of the pharmacokinetic and pharmacodynamics profiles of these compounds will support more effective clinical trials in the future.…”

Section: Limitations and Future Prospectsmentioning

confidence: 99%

Therapeutic roles of natural remedies in combating hereditary ataxia: A systematic review

et al. 2021

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Background Hereditary ataxia (HA) represents a group of genetically heterogeneous neurodegenerative diseases caused by dysfunction of the cerebellum or disruption of the connection between the cerebellum and other areas of the central nervous system. Phenotypic manifestation of HA includes unsteadiness of stance and gait, dysarthria, nystagmus, dysmetria and complaints of clumsiness. There are no specific treatments for HA. Management strategies provide supportive treatment to reduce symptoms. Objectives This systematic review aimed to identify, evaluate and summarise the published literature on the therapeutic roles of natural remedies in the treatment of HA to provide evidence for clinical practice. Methods A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Web of Science, PubMed and Science Direct Scopus were thoroughly searched for relevant published articles from June 2007 to July 2020. Results Ten pre-clinical and two clinical studies were eligible for inclusion in this systematic review. We identified the therapeutic roles of medicinal plants Brassica napus, Gardenia jasminoides, Gastrodia elata, Ginkgo biloba, Glycyrrhiza inflata, Paeonia lactiflora, Pueraria lobata and Rehmannia glutinosa; herbal formulations Shaoyao Gancao Tang and Zhengan Xifeng Tang; and medicinal mushroom Hericium erinaceus in the treatment of HA. In this review, we evaluated the mode of actions contributing to their therapeutic effects, including activation of the ubiquitin–proteasome system, activation of antioxidant pathways, maintenance of intracellular calcium homeostasis and regulation of chaperones. We also briefly highlighted the integral cellular signalling pathways responsible for orchestrating the mode of actions. Conclusion We reviewed the therapeutic roles of natural remedies in improving or halting the progression of HA, which warrant further study for applications into clinical practice.

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Chinese Medicine: A Hope for Neurodegenerative Diseases?

Cited by 17 publications

References 82 publications

Systems Pharmacology Approach to Investigate the Mechanism of Kai-Xin-San in Alzheimer’s Disease

Systems Pharmacology Approach to Investigate the Mechanism of Kai-Xin-San in Alzheimer’s Disease

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

Therapeutic roles of natural remedies in combating hereditary ataxia: A systematic review

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