Dataset Information

A Tau Pathogenesis-Based Network Pharmacology Approach for Exploring the Protections of Chuanxiong Rhizoma in Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia and one of the top medical concerns worldwide. Currently, the approved drugs to treat AD are effective only in treating the symptoms, but do not cure or prevent AD. Although the exact causes of AD are not understood, it is recognized that tau aggregation in neurons plays a key role. Chuanxiong Rhizoma (CR) has been widely reported as effective for brain diseases such as dementia. Thus, we explored the protections of CR in AD by a tau pathogenesis-based network pharmacology approach. According to ultra-HPLC with triple quadrupole mass spectrometry data and Lipinski's rule of five, 18 bioactive phytochemicals of CR were screened out. They were shown corresponding to 127 tau pathogenesis-related targets, among which VEGFA, IL1B, CTNNB1, JUN, ESR1, STAT3, APP, BCL2L1, PTGS2, and PPARG were identified as the core ones. We further analyzed the specific actions of CR-active phytochemicals on tau pathogenesis from the aspects of tau aggregation and tau-mediated toxicities. It was shown that neocnidilide, ferulic acid, coniferyl ferulate, levistilide A, Z-ligustilide, butylidenephthalide, and caffeic acid can be effective in reversing tau hyperphosphorylation. Neocnidilide, senkyunolide A, butylphthalide, butylidenephthalide, Z-ligustilide, and L-tryptophan may be effective in promoting lysosome-associated degradation of tau, and levistilide A, neocnidilide, ferulic acid, L-tryptophan, senkyunolide A, Z-ligustilide, and butylidenephthalide may antagonize tau-mediated impairments of intracellular transport, axon and synaptic damages, and neuron death (especially apoptosis). The present study suggests that acting on tau aggregation and tau-mediated toxicities is part of the therapeutic mechanism of CR against AD.

SUBMITTER: Zeng P

PROVIDER: S-EPMC9068950 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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A Tau Pathogenesis-Based Network Pharmacology Approach for Exploring the Protections of <i>Chuanxiong Rhizoma</i> in Alzheimer's Disease.

Zeng Peng P Su Hong-Fei HF Ye Chao-Yuan CY Qiu Shuo-Wen SW Shi Anbing A Wang Jian-Zhi JZ Zhou Xin-Wen XW Tian Qing Q

Frontiers in pharmacology 20220421

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia and one of the top medical concerns worldwide. Currently, the approved drugs to treat AD are effective only in treating the symptoms, but do not cure or prevent AD. Although the exact causes of AD are not understood, it is recognized that tau aggregation in neurons plays a key role. <i>Chuanxiong Rhizoma</i> (CR) has been widely reported as effective for brain diseases such as dementia. Thus, we explored the protecti ...[more]

PMID: 35529440

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Project description:Explore Acori Tatarinowii Rhizoma (ATR) and Polygalae Radix (PR) mechanisms in Alzheimer's disease (AD) treatment through network pharmacology. ATR-PR was investigated in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, Batman, and Traditional Chinese Medicines Integrated Database (TCMID) to gather information on its chemical components and target proteins. Target genes associated with AD were retrieved from the GeneCards and National Center for Biotechnology Information (NCBI) databases. The integration of these datasets with potential targets facilitated the construction of an AD and ATR-PR protein-protein interaction (PPI) network using the STRING database. The resulting network identified the core active ingredients and main targets of ATR-PR in AD treatment. Cluster analysis of the PPI network was performed using Cytoscape 3.7.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Metascape database. Molecular docking simulations revealed potential interactions between the main active ingredients and core targets. Our analysis identified 8 putative components and 455 targets of ATR-PR. We systematically searched for 1306 genes associated with AD, conducted Venn diagram analysis resulting in 156 common targets, and constructed a PPI network with 57 key targets. GO functional analysis highlighted the primary biological processes associated with oxidative stress. KEGG pathway enrichment analysis revealed the involvement of 64 signaling pathways, with the PI3K/Akt signaling pathway playing a key role. Molecular docking analysis indicated a high affinity between the potential targets of ATR-PR and the main compounds of AD. This study sheds light on the complex network of interactions involving ATR-PR in the context of AD. The identified targets, pathways, and interactions provide a foundation for understanding the potential therapeutic mechanisms. The involvement of oxidative stress-related processes and the crucial role of the PI3K/Akt signaling pathway suggest avenues for targeted therapeutic interventions in Alzheimer's disease treatment. Our proposition of the combined use of ATR-PR has emerged as a potential treatment strategy for AD, supported by a network pharmacology approach. This framework provides a robust foundation for future clinical applications and experimental research in the pursuit of effective Alzheimer's disease treatments.

Project description:Migraine is a common neurological disorder that manifests as recurrent attacks of unilateral and throbbing headache. Conioselinum anthriscoides "Chuanxiong" (Apiaceae; Chuanxiong rhizoma) and Cyperus rotundus L. (Cyperaceae; Cyperi rhizoma) (CRCR), is a classic prescription for treating migraine. This study aimed to reveal the potential mechanisms of CRCR extract against migraine using integrated analysis of metabolomics and network pharmacology. Behavioral changes in the nitroglycerin rat migraine model were determined from von Frey withdrawal response. Untargeted serum metabolomics was used to identify the differentially expressed metabolites and metabolic pathways. The differentially expressed metabolites were analyzed to obtain the corresponding targets by a compound-reaction-enzyme-gene network. Network pharmacology was used to construct a compound-target-pathway network. The common targets of metabolomics and network pharmacology were further analyzed. Metabolomics analysis identified 96 differentially expressed metabolites and 77 corresponding targets. Network pharmacology analysis identified 201 potential targets for CRCR against migraine. By intersecting 77 targets with 201 targets, monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), and catechol-O-methyltransferase (COMT) were identified as the common targets, and MAO-A, MAO-B, and COMT were involved in the tyrosine metabolism pathway. Further experiments demonstrated that the contents of MAO-A and COMT were significantly increased in serum and brainstem tissue of the migraine rats. CRCR extract significantly decreased the contents of MAO-A and COMT, while no significant difference was found in MAO-B. Metabolomics analysis indicated that the contents of 3,4-dihydroxyphenylacetate (DOPAC) and 3-(4-hydroxyphenyl)pyruvate (HPP) were significantly increased in the migraine rats, and CRCR extract caused significant decreases in DOPAC and HPP. Interestingly, DOPAC and HPP were two differentially expressed metabolites involved in the tyrosine metabolism pathway. Correlation analysis showed that DOPAC and HPP were highly positively correlated with MAO-A and COMT. Taken together, two key differentially expressed metabolites (DOPAC and HPP), two key targets (MAO-A and COMT), and one relevant metabolic pathway (tyrosine metabolism) showed great importance in the treatment of migraine. This research could provide a new understanding of the potential mechanism of CRCR against migraine. More attentions should be paid into the tyrosine metabolism pathway in future studies.

Project description:BackgroundChuanxiong Rhizoma (CR) is a common traditional Chinese medicine (TCM) that has been widely used in the treatment of spinal cord injury (SCI). However, the underlying molecular mechanism of CR is still largely unknown. This study was designed to explore the bioactive components and the mechanism of CR in treating SCI based on a network pharmacology approach and experimental validation.MethodsFirst, the active compounds and related target genes in CR were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the corresponding target genes of SCI were collected by the Therapeutic Target Database (TTD) and GeneCards database. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, GO function and KEGG enrichment analysis of the targets were analyzed using DAVID tools. Subsequently, the AutoDock software for molecular docking was adopted to verify the above network pharmacology analysis results between the active components and key targets. Finally, an SCI rat model animal validation experiment was assessed to verify the reliability of the network pharmacology results.ResultsThere were 7 active ingredients identified in CR and 246 SCI-related targets were collected. Then, 4 core nodes (ALB, AKT1, MAPK1, and EGFR) were discerned via construction of a PPI network of 111 common targets. The KEGG enrichment analysis results indicated that the Ras signaling pathway, estrogen signaling pathway, and vascular endothelial growth factor (VEGF) signaling pathway were enriched in the development of SCI. The results of molecular docking demonstrated that the effects of CR have a strong affinity with the 4 pivotal targets. Experimental validation in a rat model showed that CR could effectively improve the recovery of motor function and mechanical pain threshold after SCI.ConclusionsIn summary, it revealed the mechanism of CR treatment for SCI involve active ingredients, targets and signaling pathways, providing a scientific basis for future investigations into the mechanism underlying CR treating for SCI.

Dataset Information

A Tau Pathogenesis-Based Network Pharmacology Approach for Exploring the Protections of Chuanxiong Rhizoma in Alzheimer's Disease.

Publications

A Tau Pathogenesis-Based Network Pharmacology Approach for Exploring the Protections of <i>Chuanxiong Rhizoma</i> in Alzheimer's Disease.

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