首页|Banxia Xiexin Decoction Alleviated Cerebral Glucose Metabolism Disorder by Regulating Intestinal Microbiota in APP/PS1 Mice

Banxia Xiexin Decoction Alleviated Cerebral Glucose Metabolism Disorder by Regulating Intestinal Microbiota in APP/PS1 Mice

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Objective:To identify whether Banxia Xiexin Decoction(BXD)alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice.Methods:Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table(n=15 per group),including a model group(MG),a liraglutide group(LG)and a BXD group(BG).Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group(CG).Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg-d)for 3 months,while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection(25 nmol/kg)for 3 months.Firstly,liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD.Then,the cognitive deficits,A β pathological change and synaptic plasticity markers,including synaptophysin(SYP)and postsynaptic density protein 95(PSD95),were measured in APP/PS1 mice.Brain glucose uptake was detected by micro-positron emission tomography.Intestinal microbial constituents were detected by 16S rRNA sequencing.The levels of intestinal glucagon-like peptide 1(GLP-1)and cerebral GLP-1 receptor(GLP-1R),as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3 β(PI3K/Akt/GSK3 β)insulin signaling pathway were determined by immunohistochemical(IHC)staining and Western blot analysis,respectively.Results:BXD ameliorated cognitive deficits and Aβ pathological features(P＜0.01).The expressions of SYP and PSD95 in the BG were higher than those in the MG(P＜0.01).Brain glucose uptake in the BG was higher than that in the MG(P＜0.01).The intestinal microbial composition in the BG was partially reversed.The levels of intestinal GLP-1 in the BG were higher than those in the MG(P＜0.01).Compared with the MG,the expression levels of hippocampal GLP-1 R,Akt,P13K and p-PI3K in the BG were significantly increased(P＜0.01),while the levels of GSK3β were reduced(P＜0.01).Conclusion:BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R,enhancing PI3K/Akt/GSK3 β insulin signaling pathway,and improving brain glucose metabolism.

Banxia Xiexin DecoctionAlzheimer's diseaseintestinal microbiotaglucagon-like peptide 1cerebral insulin resistancephosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3 βChinese medicine

GAO Chen-yan、QIN Gao-feng、ZHENG Ming-cui、TIAN Mei-jing、HE Yan-nan、WANG Peng-wen

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Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China

Neurology Department,Binzhou Medical University Hospital,Binzhou,Shandong Province(256603),China

Special Fund for Basic Scientific Research Operating Fees of Central Universities

2019-BUCMXJKY018

2024

10.1007/s11655-023-3606-3

中国结合医学杂志(英文版)
中国中西医结合学会 中国中医研究院

中国结合医学杂志(英文版)

CSTPCD
影响因子：1.056
ISSN：1672-0415
年,卷(期)：2024.30(8)