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A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.

ABSTRACT: Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and β-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders.

SUBMITTER: Mao J

PROVIDER: S-EPMC4568966 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.

Mao Jianxin J Huang Shichao S Liu Shangfeng S Feng Xiao-Lin XL Yu Miao M Liu Junjun J Sun Yi Eve YE Chen Guoliang G Yu Yang Y Zhao Jian J Pei Gang G

Aging cell 20150525 5

Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the h ...[more]

PMID: 26010330

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Project description:Background: Multiple systematic reviews (SRs) have been conducted to evaluate the efficacy and safety of Chinese herbal medicine (CHM) in patients with Alzheimer's disease (AD). Here, we aim to perform an overview to assess the methodological quality and quality of evidence of the SRs to provide convincing data on the treatment of AD with CHM. Method: Six electronic databases including Chinese and English were searched, until April 31, 2021. Two researchers independently screen documents and extract data according to the predesigned rules. A Measure Tool to Assessment System Reviews 2 (AMSTAR-2) was used to investigate the methodological quality, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to determine the quality of evidence for outcomes. Results: Twelve qualified SRs including 163 randomized controlled trials were reviewed. The methodological quality of the included SRs was considered extremely low assessed through AMSTAR-2. Compared with western medicines (WM) alone, CHM as an adjuvant treatment has shown significant effects in improving Mini-mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive, and Clinical Dementia Rating scores. The same is true for CHM alone. Regarding the effect on Activities Daily Living, neither the single CHM nor the combination with WM has an obvious effect. For the total effective rate, both single CHM and the combination with WM shown significant effects. Nine SRs suggested that CHM as adjuvant therapy or single-use had fewer adverse events than WM. Additionally, the quality of evidence for the main outcome was reviewed as low or extremely low according to GRADE profiler data. Conclusion: Current evidence suggests that CHM may be beneficial in improving the cognitive function of AD patients. However, we should be cautious about the evidence due to methodological flaws and low quality. High-quality RCTs are further needed to confirm the efficacy and safety of CHM for AD.

Project description:BackgroundNeuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system.MethodologyWe have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain.ResultsWe have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo.ConclusionsThis work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical agents to facilitate neuronal renewal.

Project description:BackgroundGlioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs' alteration remain unkown.MethodsWe collected EVs in the culture medium of three classic glioblastoma cell lines, U87 and A172 (male cell lines), and LN229 (female cell line). U87, A172, and LN229 were co-cultured with their corresponding EVs, respectively. Mouse NPCs (mNPCs) were co-cultured with glioblastoma-derived EVs. The proliferation and migration of tumor cells and mNPCs after EVs treatment were examined. Proteomic analysis and western blotting were utilized to identify the underlying mechanisms of glioblastoma-derived EVs-induced alterations in mNPCs.ResultsWe first show that glioblastoma cell lines U87-, A172-, and LN229-derived EVs were essential for glioblastoma cell prolifeartion and migration. We then demonstrated that glioblastoma-derived EVs dramatically promoted NPC proliferation and migration. Mechanistic studies identify that glioblastoma-derived EVs achieve their functions via activating PI3K-Akt-mTOR pathway in mNPCs. Inhibiting PI3K-Akt pathway reversed the elevated prolfieration and migration of glioblastoma-derived EVs-treated mNPCs.ConclusionOur findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy. Video Abstract.

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A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.

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A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.

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