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

Zeng, Peng; Ye, Chao-Yuan; Qiu, Shuo-Wen; Shi, Anbing; Wang, Jian‐Zhi; Zhou, Xin‐Wen; Tian, Qing

doi:10.3389/fphar.2022.877806

Cited by 12 publications

(12 citation statements)

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“…Network pharmacology is a novel multi-target therapeutic molecule design technique based on systems biology theory, network analysis of biological systems, and identifying particular signal nodes ( Khanal and Patil, 2021 ; Zeng et al, 2022 ). It focuses on multimodal regulation of signal transduction pathways to maximize therapeutic efficacy while avoiding collateral side responses ( Hopkins, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo

Tang

Wang²,

Sun³

et al. 2022

Front. Pharmacol.

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Acute-on-chronic liver failure (ACLF) is characterized by undermined liver function, massive necrosis/apoptosis of hepatocytes, and hepatic inflammatory cell recruitment, leading to multiorgan failure. Traditional Chinese medicine (TCM) has been widely applied in clinical and experimental studies of ACLF. In this study, 23 compounds with 6,386 drug targets were obtained from Wenyang Jiedu Huayu (WYJDHY), and 8,096 genes were identified as ACLF disease targets, among which 3,132 were overlapping co-targets. Expression profile analysis identified 105 DEGs among the co-targets, which were associated with biological activities such as lymphocyte activation, immune response regulation, and pathways such as Th17 cell differentiation and NF-κB signaling. After PPI analysis and network construction, atractylenolide I (AT-1) has been identified as the hub active ingredient of the WYJDHY formula. LPS stimulation inhibited rat hepatocytes’ BRL 3A cell viability, promoted cell apoptosis, increased the levels of ALT, AST, IL-6, and VCAM-1 within the culture medium, and activated NF-κB signaling, whereas AT-1 treatment significantly attenuated LPS-induced toxicity on BRL 3A cells. Furthermore, the NF-κB signaling inhibitor PDTC exerted effects on LPS-stimulated BRL 3A cells similar to those of AT-1, and the combination of PDTC and AT-1 further attenuated LPS-induced toxicity on BRL 3A cells. In vivo, AT-1 alone or with PDTC improved the symptoms and local inflammation in ACLF model rats. In conclusion, 23 active ingredients of six herbs in the WYJDHY formula were retrieved, and 105 co-targets were differentially expressed in ACLF. AT-1 exerts protective effects on LPS-stimulated hepatocytes and ACLF rats, possibly by inhibiting the NF-κB pathway.

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Section: Introductionmentioning

confidence: 99%

Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo

Tang

Wang²,

Sun³

et al. 2022

Front. Pharmacol.

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“…The keywords “Phellodendron, Pulsatilla, Coptis Chinensis, and Cortex Fraxini” were searched accordingly on the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) ( https://lsp.nwu.edu.cn/tcmsp.php ) ( Yang et al, 2017 ; Zeng et al, 2022 ) to obtain all the chemical components of PD. Moreover, all chemical components were screened for active ingredients according to the screening criteria of bioactive components with oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18.…”

Section: Methodsmentioning

confidence: 99%

Network pharmacology and molecular docking to elucidate the mechanism of pulsatilla decoction in the treatment of colon cancer

Liu

et al. 2022

Front. Pharmacol.

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Objective: Colon cancer is a malignant neoplastic disease that seriously endangers the health of patients. Pulsatilla decoction (PD) has some therapeutic effects on colon cancer. This study is based on the analytical methods of network pharmacology and molecular docking to study the mechanism of PD in the treatment of colon cancer.Methods: Based on the Traditional Chinese Medicine Systems Pharmacology Database, the main targets and active ingredients in PD were filtered, and then, the colon cancer-related targets were screened using Genecards, OMIM, PharmGKB, and Drugbank databases. Then, the screened drug and disease targets were Venn analyzed to obtain the intersection targets. Cytoscape software was used to construct the “Components–Targets–Pathway” map, and the String database was used to analyze the protein interaction network of the intersecting targets and screen the core targets, and then, the core targets were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was implemented using AutoDockTools to predict the binding capacity for the core targets and the active components in PD.Results: Sixty-five ingredients containing 188 nonrepetitive targets were screened and 180 potential targets of PD anticolon cancer were identified, including 10 core targets, namely, MAPK1, JUN, AKT1, TP53, TNF, RELA, MAPK14, CXCL8, ESR1, and FOS. The results of GO analysis showed that PD anticolon cancer may be related to cell proliferation, apoptosis, energy metabolism, immune regulation, signal transduction, and other biological processes. The results of KEGG analysis indicated that the PI3K-Akt signaling pathway, MAPK signaling pathway, proteoglycans in cancer, IL-17 signaling pathway, cellular senescence, and TNF signaling pathway were mainly involved in the regulation of tumor cells. We further selected core targets with high degree values as receptor proteins for molecular docking with the main active ingredients of the drug, including MAPK1, JUN, and AKT1. The docking results showed good affinity, especially quercetin.Conclusion: This study preliminarily verified that PD may exert its effect on the treatment of colon cancer through multi-ingredients, multitargets, and multipathways. This will deepen our understanding of the potential mechanisms of PD anticolon cancer and establish a foundation for further basic experimental research.

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“…The ratio of the gene numbers to all gene numbers annotated in this term is the rich factor. The top 10 enriched terms of CUR targets were visualized using a web-based tool (www.bioinformatics.com.cn) (Zeng et al, 2022). We also downloaded the genes of PI3K-Akt signaling pathway from the PathCards database (http://pathcards.genecards.org/) (Belinky et al, 2015).…”

Section: Kyoto Encyclopedia Of Genes and Genomes (Kegg) Pathway Enric...mentioning

confidence: 99%

Mechanistic insights into the anti-depressant effect of curcumin based on network pharmacology and experimental validation

Guo

Fang

Xiong

et al. 2023

Preprint

Self Cite

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Growing evidence supports the involvement of neuroinflammation in the pathophysiology of depression. Administrating curcumin could revert the depressive-like symptoms and weakened microglial activation and increased the level of pro-inflammatory cytokine. This study aimed to identify potential anti-depression targets and mechanisms of curcumin (CUR) by an approach of network pharmacology. GSEA and KEGG pathways showed the most significantly enriched pathway of CUR against depression was the PI3K-Akt pathway. Moreover, 52 targets were significantly correlated with PI3K-Akt signaling pathway and CUR-related targets. In addition, among these top 50 targets which were ranked by degree in the PPI network, there were 23 targets involved in the 52 intersection targets. Thus, our findings suggest that CUR exerts its anti-depression effects through PI3K-Akt signaling pathway. Furthermore, we investigated the anti-depression effects of CUR using a mouse model of depression induced by lipopolysaccharide (LPS). Administration of LPS alone (2 mg/kg/day, i.p.) extended the immobility time in the open filed test (OFT) and tail suspension test (TST), decreased sucrose consumption in the sucrose preference test (SPT). Pretreatment with CUR (50 mg/kg/day, i.p.) for 7 consecutive days relieved LPS-induced changes in the behavior tests, the activity of PI3K-Akt signaling pathway, neuronal damage in the PFC and inflammatory response. Moreover, inhibition of the PI3K-Akt signaling pathway by LY294002 (7.5 mg/kg/day, i.p.) blocks the therapeutic effects of CUR. In conclusion, our study indicate that CUR may be an effective antidepressant agent for LPS-induced mouse model, in part because of its anti-inflammatory actin through PI3K-Akt signaling pathway.

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

Cited by 12 publications

References 84 publications

Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo

Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo

Network pharmacology and molecular docking to elucidate the mechanism of pulsatilla decoction in the treatment of colon cancer

Mechanistic insights into the anti-depressant effect of curcumin based on network pharmacology and experimental validation

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