Integrated network pharmacology analysis and serum metabolomics to reveal the cognitive improvement effect of Bushen Tiansui formula on Alzheimer's disease

Zhang, Zheyu; Yi, Pan; Yang, Jingjing; Huang, Jianhua; Xu, Panpan; Hu, Muli; Zhang, Chunhu; Wang, Bing; Peng, Weijun

doi:10.1016/j.jep.2019.112371

Cited by 66 publications

(48 citation statements)

References 51 publications

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“…(Shichangpu), Plastrum testudinis (Guiban), and Ossa draconis (Longgu). We recently showed that BSTSF could improve learning and memory deficits in AD model rats through regulating serum lipid metabolism and the amino acid metabolic pathway [4]. However, the mechanism underlying the therapeutic effects of BSTSF, especially its effects on metabolic stress and impaired lipid metabolism in brain tissue, is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Integrated Metabolomic and Lipidomic Analysis Reveals the Neuroprotective Mechanisms of Bushen Tiansui Formula in an Aβ1-42-Induced Rat Model of Alzheimer’s Disease

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Bushen Tiansui Formula (BSTSF) is a traditional Chinese medicine prescription. It has been widely applied to treat Alzheimer’s disease (AD) in the clinic; however, the mechanisms underlying its effects remain largely unknown. In this study, we used a rat AD model to study the effects of BSTSF on cognitive performance, and UPLC-MS/MS-based metabolomic and lipidomic analysis was further performed to identify significantly altered metabolites in the cerebral cortices of AD rats and determine the effects of BSTSF on the metabolomic and lipidomic profiles in the cerebral cortices of these animals. The results revealed that the levels of 47 metabolites and 30 lipids primarily associated with sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism were significantly changed in the cerebral cortices of AD rats. Among the altered lipids, ceramides, phosphatidylethanolamines, lysophosphatidylethanolamines, phosphatidylcholines, lysophosphatidylcholines, phosphatidylserines, sphingomyelins, and phosphatidylglycerols showed robust changes. Moreover, 34 differential endogenous metabolites and 21 lipids, of which the levels were mostly improved in the BSTSF treatment group, were identified as potential therapeutic targets of BSTSF against AD. Our results suggest that lipid metabolism is highly dysregulated in the cerebral cortices of AD rats, and BSTSF may exert its neuroprotective mechanisms by restoring metabolic balance, including that of sphingolipid metabolism, glycerophospholipid metabolism, alanine, aspartate, and glutamate metabolism, and D-glutamine and D-glutamate metabolism. Our data may lead to a deeper understanding of the AD-associated metabolic profile and shed new light on the mechanism underlying the therapeutic effects of BSTSF.

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Section: Introductionmentioning

confidence: 99%

Integrated Metabolomic and Lipidomic Analysis Reveals the Neuroprotective Mechanisms of Bushen Tiansui Formula in an Aβ1-42-Induced Rat Model of Alzheimer’s Disease

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Disease targets were retrieved from GeneCards ( http://www.genecards.org ) and Online Mendelian Inheritance in Man (OMIM, http://www.omim.org ) [ 27 ]. We searched these databases using the keywords “gastric cancer” and “stomach cancer”.…”

Section: Methodsmentioning

confidence: 99%

A Network Pharmacology Analysis of the Active Components of the Traditional Chinese Medicine Zuojinwan in Patients with Gastric Cancer

Zhang

Huang

et al. 2020

Med Sci Monit

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Background Zuojinwan (ZJW) is a traditional Chinese prescription normally used for gastritis. Several studies indicated that it could fight against gastric cancer. This study was designed to determine the potential pharmacological mechanism of ZJW in the treatment of gastric cancer. Material/Methods Bioactive compounds and potential targets of ZJW and related genes of gastric cancer were retrieved from public databases. Pharmacological mechanisms including crucial ingredients, potential targets, and signaling pathways were determined using protein-protein interaction (PPI) and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Virtual docking was performed to validate the findings. Results Network analysis identified 47 active ZJW compounds, and 48 potential ZJW target genes linked to gastric cancer. Quercetin, beta-sitosterol, isorhamnetin, wogonin, and baicalein were identified as potential candidate agents. Our PPI analysis results combined with previously published results indicated that matrix metalloproteinases family members MMP9, MMP1, and MMP3 may play key roles in the anti-gastric cancer effect of ZJW. Molecular docking analysis showed that these crucial targets had good affinity for the representative components in ZJW. GO and KEGG enrichment analysis showed that ZJW target genes functioned in multiple pathways for treating gastric cancer, including interleukin-17 signaling and platinum drug resistance. Conclusions Our results illuminate the active ingredients, associated targets, biological processes, and signaling pathways of ZJW in the treatment of gastric cancer. This study enhances our understanding of the potential effects of ZJW in gastric cancer and demonstrates a feasible method for discovering potential drugs from Chinese medicinal formulas.

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“…Network pharmacology is a novel method that combines computer science with medicine. Based on" multi-gene, multi-target, multi-pathway" interaction network, network pharmacology combined with TCM provides an in-depth understanding of the active ingredients in Chinese herbs [16]. Besides, this also provides potent evidence into biological targets and the underlying mechanism of action of TCM in the treatment of various diseases [17].…”

Section: Introductionmentioning

confidence: 99%

Application of network pharmacology and molecular docking to elucidate the potential mechanism of Eucommia ulmoides-Radix Achyranthis Bidentatae against osteoarthritis

Jian

Zhou

et al. 2020

BioData Mining

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Background: Osteoarthritis is a disabling disease, which seriously affects the quality of life of patients. Increasing evidence has indicated that Chinese herbal medicine including Eucommia ulmoides (EU) and Radix Achyranthis Bidentatae (RAB) have potential in the treatment of osteoarthritis, and this is associated with their multitarget and multi-link action characteristics. Although their potential anti-arthritic activity has been reported, the exact mechanism of EU-RAB action in osteoarthritis remains unexplored. Therefore, this study explores the mechanism of EU-RAB against osteoarthritis using network pharmacology and molecular docking technology. Methods: Public databases including TCMSP、BATMAN-TCM、OMIM and Genecards were used to predict the bioactive ingredients and putative targets of EU-RAB against osteoarthritis. Enrichment analysis was performed to expound the biological functions and associated pathways of the hub targets. Cytoscape software was used to construct a "compounds-targets-pathways" network for elucidating the comprehensive molecular mechanism of EU-RAB against osteoarthritis. Molecular docking was used to verify the correlation between the main active ingredients and hub targets. Results: Network pharmacological analysis of EU-RAB in the treatment of osteoarthritis, identified 50 active ingredients including quercetin, kaempferol, wogonin, and baicalein with important biological effect. A total of 68 key targets were screened, including IL-6, EGFR, MAPK8, etc., and they were found to be enriched in a series of signaling pathways, such as apoptosis, TNF, MAPK, PI3K/AKT, and IL-17 signaling pathways. Moreover, molecular docking analysis showed that the main ingredients were tightly bound to the core targets, further confirming the anti-arthritic effects.

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Integrated network pharmacology analysis and serum metabolomics to reveal the cognitive improvement effect of Bushen Tiansui formula on Alzheimer's disease

Cited by 66 publications

References 51 publications

Integrated Metabolomic and Lipidomic Analysis Reveals the Neuroprotective Mechanisms of Bushen Tiansui Formula in an Aβ1-42-Induced Rat Model of Alzheimer’s Disease

Integrated Metabolomic and Lipidomic Analysis Reveals the Neuroprotective Mechanisms of Bushen Tiansui Formula in an Aβ1-42-Induced Rat Model of Alzheimer’s Disease

A Network Pharmacology Analysis of the Active Components of the Traditional Chinese Medicine Zuojinwan in Patients with Gastric Cancer

Application of network pharmacology and molecular docking to elucidate the potential mechanism of Eucommia ulmoides-Radix Achyranthis Bidentatae against osteoarthritis

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