Dataset Information

Effcacy-oriented compatibility for Tianma (), Yanlingcao () and Bingpian () on improving cerebral ischemia stroke by network pharmacology and serum pharmacological methods.

ABSTRACT:

Objective

To evaluate the compatibility of Tianma (, TM), Yanlingcao (, YLC) and Bingpian (, BP), and their efficacy in the treatment of cerebral ischemic stroke.

Methods

Network pharmacology was used to determine the compatibility of TM, YLC, and BP, and their potential mechanism. The middle cerebral artery occlusion (MCAO) rat model was used to evaluate the curative effect of the six combinations of TM, YLC, and BP (TZB1-TZB6) on cerebral ischemia, by using the weight matching method to form. The potential component changes of TM and YLC in the blood and brains of rats were analyzed using ultra performance liquid chromatography-mass spectrometry. Finally, molecular docking linked the results of animal experiments and network pharmacology, determining the potential component contributors of TM and YLC to treating ischemic stroke.

Results

TZB reduced the cerebral infarct volume and protected the nerve cells in MCAO rats. The components of TM and YLC were also identified in the blood and brain homogenate, and BP can facilitate the entry of the components of TM and YLC into the blood and brain. Diosgenin, pennogenin, and gastrodin induced effective binding activities with adenosine receptor a1.

Conclusion

We investigate an approach that improves the means of folk prescription combined with multi technology that maybe promote the transformation of Chinese medicinal prescription into component-based Chinese medicine.

SUBMITTER: Zhiyong LI

PROVIDER: S-EPMC9924670 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Effcacy-oriented compatibility for Tianma (), Yanlingcao () and Bingpian () on improving cerebral ischemia stroke by network pharmacology and serum pharmacological methods.

Zhiyong L I LI Na Zhu Z Jianliang L I LI Liang Feng F Yanyan Jiang J Caifeng L I LI Ling Lin L Xiulan Huang H

Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan 20220601 3

<h4>Objective</h4>To evaluate the compatibility of Tianma (, TM), Yanlingcao (, YLC) and Bingpian (, BP), and their efficacy in the treatment of cerebral ischemic stroke.<h4>Methods</h4>Network pharmacology was used to determine the compatibility of TM, YLC, and BP, and their potential mechanism. The middle cerebral artery occlusion (MCAO) rat model was used to evaluate the curative effect of the six combinations of TM, YLC, and BP (TZB1-TZB6) on cerebral ischemia, by using the weight matching m ...[more]

PMID: 35610010

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Project description:BackgroundIschemic stroke (IS) is a serious disease with a high rate of death and disability, and a growing number of people are becoming victims. Existing drugs not only have limited therapeutic effects but also have obvious side effects. Most importantly, drug resistance due to long-term or improper use of drugs is detrimental to patients. Therefore, it is urgent to find some alternative or supplementary medicines to alleviate the current embarrassment. Powerful Tianma Eucommia Capsule (PTEC) is mainly used to treat IS in China for thousands of years; however, the molecular mechanism is not clear.MethodsPharmacology ingredients and target genes were filtered and downloaded from websites. A pharmacology ingredient-target gene network was constructed to predict the molecular interactions between ingredients and target genes. Enrichment analysis was performed to explore the possible signal pathways. LeDock was used to simulate the interaction form between proteins and main active ingredients and to deduce key amino acid positions.ResultsTwo hundred eighty-nine target genes and seventy-four pharmacological ingredients were obtained from public databases. Several key ingredients (quercetin, kaempferol, and stigmasterol) and primary core target genes (PTGS1, NCOA2, and PRSS1) were detected through ingredient-target gene network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that ingredients affect networks mainly in nuclear receptor activity and G protein-coupled amine receptor activity; besides, fluid shear stress and atherosclerosis, human cytomegalovirus infection, and hepatitis B signaling pathways might be the principal therapy ways. A series of presumed key amino acid sites (189ASP, 190SER, 192GLN, 57HIS, and 99TYE) were calculated in PRSS1. Six of the target genes were differentially expressed between male and female patients.ConclusionsSeven new putative target genes (ACHE, ADRA1A, AR, CHRM3, F7, GABRA1, and PRSS1) were observed in this work. Based on the result of GO and KEGG analysis, this work will be helpful to further demonstrate the molecular mechanism of PTEC treatment of IS.

Project description:Cerebral infarction (CI), a common cerebrovascular disease worldwide, is caused by unknown factors common to many diseases, including hypokalemia, respiratory diseases, and lower extremity venous thrombosis. Tianma Gouteng (TMGT), a traditional Chinese Medicine (TCM) prescription, has been used for the clinical treatment of CI. In this study, high-performance liquid chromatography (HPLC) fingerprint analysis was used to detect and identify major chemical constituents of TMGT. TCMSP and BATMAN-TCM databases were used to screen for active TMGT constituent compounds, while the GeneCards database was used to screen for protein targets associated with CI. Next, GO and KEGG enrichment analysis of these core nodes were performed to determine the identities of key associated biological processes and signal pathways. Meanwhile, a total of six possible gene targets of TMGT, including NFKBIA, PPARG, IL6, IL1B, CXCL8, and HIF1A, were selected for further study using two cellular models of CI. For one model, PC12 cells were treated under oxygen and glucose deprivation (OGD) conditions to generate an OGD cellular model of CI, while for the other model, BV2 cells were stimulated with lipopolysaccharide (LPS) to generate a cellular model of CI-associated inflammation. Ultimately TMGT treatment increased PPARγ expression and downregulated the expression of p-P65, p-IκBα, and HIF-1α in both OGD-induced and LPS-induced cell models of CI. In addition, molecular docking analysis showed that one TMGT chemical constituent, quercetin, may be a bioactive TMGT compound with activity that may be associated with the alleviation of neuronal damage and neuroinflammation triggered by CI. Moreover, additional data obtained in this work revealed that TMGT could inhibit neuroinflammation and protect brain cells from OGD-induced and LPS-induced damage by altering HIF-1α/PPARγ/NF-κB pathway functions. Thus, targeting this pathway through TMGT administration to CI patients may be a strategy for alleviating nerve injury and neuroinflammation triggered by CI.

Project description:3,4‑Dihydroxybenzaldehyde (DBD), one of the active components of Gastrodia elata, has a cerebral protective effect and can effectively combat cerebral ischemia/reperfusion (I/R) injury in rats. However, the metabolite profiles and underlying mechanisms associated with DBD remain unclear. To explore the level of energy metabolism and pharmacological targets in brain tissue following DBD treatment of stroke. The right middle cerebral artery of the rats was occluded for 2 h and reperfused for 24 h to simulate brain I/R injury. Pharmacological results showed that DBD reduced cerebral infarct volume, improved neurological function and increased adenosine triphosphate (ATP) content. Mitochondria are the primary sites for ATP generation and cellular energy supply and decreasing mitochondrial dysfunction can alleviate the energy expenditure of ischemic stroke. Through further experiments, it was found that mitochondrial damage was recovered following DBD treatment, which was manifested by the improvement of mitochondrial morphology under an electron microscope and the reduction of oxidative stress damage. The metabolomics of middle cerebral artery occlusion/reperfusion (MCAO/R) rat brain tissue was studied by the liquid chromatography‑tandem mass spectrometry metabolomics method. Significantly different metabolites were screened and the pathways involved included amino sugar and nucleotide sugar metabolism and pentose phosphate pathway. Finally, the present study performed targeted metabolic profiling and validated potential therapeutic targets. Uridine diphosphate N‑acetylglucosamine (UDP‑GlcNAc) levels were decreased in the MCAO/R group but significantly increased in the DBD group. TdT‑mediated dUTP nick end labeling (TUNEL) staining, hematoxylin and eosin staining and western blotting showed that brain cell apoptosis was inhibited and neuronal morphology improved. Among them, the regulatory enzyme O‑GlcNAc transferase (OGT) of UDP‑GlcNAc appeared to be significantly increased and neuronal apoptosis was inhibited following DBD treatment, which was verified by western blotting. Therefore, by analyzing mitochondrial dysfunction following I/R and the characterization of potential markers in mitochondrial energy metabolism, it was shown that OGT could inhibit neuronal apoptosis as a potential therapeutic target for brain I/R injury.

Dataset Information

Effcacy-oriented compatibility for Tianma (), Yanlingcao () and Bingpian () on improving cerebral ischemia stroke by network pharmacology and serum pharmacological methods.

Objective

Methods

Results

Conclusion

Publications

Effcacy-oriented compatibility for Tianma (), Yanlingcao () and Bingpian () on improving cerebral ischemia stroke by network pharmacology and serum pharmacological methods.

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