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A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Paeonia lactiflora Pall. On the Treatment of Alzheimer's Disease.

ABSTRACT: Objective:To investigate the potential active compounds and underlying mechanisms of Paeonia lactiflora Pall. (PLP) on the treatment of Alzheimer's disease (AD) based on network pharmacology. Methods:The active components of PLP were collected from Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible target proteins were predicted using TCMSP, SwissTargetPrediction, and STITCH databases. The putative AD-related target proteins were identified from Therapeutic Target Database (TTD), GeneCards, and MalaCards database. The compound-target-disease network interactions were established to obtain the key targets about PLP acting on AD by network topology analysis. Then, the function annotation and signaling pathways of key targets were performed by GO and KEGG enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking using SystemsDock tools. Results:There were 7 active compounds involving in 151 predicted targets identified in PLP. Besides, a total of 160 AD-related targets were identified. Among these targets, 30 shared targets of PLP and AD were acquired. After topological analysis of the PLP potential target-AD target network, 33 key targets that were highly responsible for the therapeutic effects of PLP on AD were obtained. Further GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in cell apoptosis and inflammatory response and maintained the function of neurons to accomplish the anti-AD activity. The molecular docking analysis verified that the 7 active compounds had definite affinity with the key targets. Conclusions:The ameliorative effects of PLP on AD were predicted to be associated with regulating neural cell apoptosis, inflammatory response, and neurotrophy via various pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, and neurotrophin signaling pathway.

SUBMITTER: Zeng Q

PROVIDER: S-EPMC6885190 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Network Pharmacology Approach to Reveal the Underlying Mechanisms of <i>Paeonia lactiflora</i> Pall. On the Treatment of Alzheimer's Disease.

Zeng Qiang Q Li Longfei L Jin Yu Y Chen Zongzheng Z Duan Lihong L Cao Meiqun M Ma Min M Wu Zhengzhi Z

Evidence-based complementary and alternative medicine : eCAM 20191116

<h4>Objective</h4>To investigate the potential active compounds and underlying mechanisms of <i>Paeonia lactiflora</i> Pall. (PLP) on the treatment of Alzheimer's disease (AD) based on network pharmacology.<h4>Methods</h4>The active components of PLP were collected from Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible target proteins were predicted using TCMSP, SwissTargetPrediction, and STITCH databases. The putative AD-related target proteins were identifie ...[more]

PMID: 31827565

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Project description:BackgroundThe incidence of allergic reaction is increasing year by year, but the specific mechanism is still unclear. Paeonia lactiflora Pall.(PLP) is a traditional Chinese medicine with various pharmacological effects such as anti-tumor, anti-inflammatory, and immune regulation. Previous studies have shown that PLP has potential anti-allergic activity. However, there is still no comprehensive analysis of the targeted effects and exact molecular mechanisms of the anti-allergic components of PLP. This study aimed to reveal the mechanism of PLP. in the treatment of type I allergy by combining network pharmacological methods and experimental verification.MethodsFirst, we used the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform to screen the main components and targets of PLP, and then used databases such as GeneCards to retrieve target information related to 'allergy'. Protein-protein interaction (PPI) analysis obtained the core target genes in the intersection target, and then imported the intersection target into the David database for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis. Furthermore, the therapeutic effect of paeoniflorin, the main component of PLP, on IgE-induced type I allergy was evaluated in vitro.ResultsGO analysis obtained the main biological processes, cell components and molecular functions involved in the target genes. KEGG analysis screened out MAPK1, MAPK10, MAPK14 and TNF that have a strong correlation with PLP anti-type I allergy, and showed that PLP may pass through signal pathways such as IgE/FcεR I, PI3K/Akt and MAPK to regulate type I allergy. RT-qPCR and Western Blot results confirmed that paeoniflorin can inhibit the expression of key genes and down-regulate the phosphorylation level of proteins in these signal pathways. It further proved the reliability of the results of network pharmacology research.ConclusionThe results of this study will provide a basis for revealing the multi-dimensional regulatory mechanism of PLP for the treatment of type I allergy and the development of new drugs.

Project description:BackgroundPaeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway.Materials and methodsLiquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico.ResultsFour major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, γ-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression.ConclusionThe potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis.

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A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Paeonia lactiflora Pall. On the Treatment of Alzheimer's Disease.

Publications

A Network Pharmacology Approach to Reveal the Underlying Mechanisms of <i>Paeonia lactiflora</i> Pall. On the Treatment of Alzheimer's Disease.

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