Dataset Information

Anti-inflammatory and Regulatory Effects of Huanglian Jiedu Decoction on Lipid Homeostasis and the TLR4/MyD88 Signaling Pathway in LPS-Induced Zebrafish.

ABSTRACT: Huanglian Jiedu decoction (HLJDD) has been used in the clinical treatment of inflammatory conditions. To clarify the mechanism of its comprehensive anti-inflammatory activities, the correlation between lipid homeostasis and the TLR4/MyD88 signaling pathway in zebrafish was established in the present study. In the lipopolysaccharide (LPS)-induced inflammation in zebrafish model, RT-PCR assays of five inflammatory cytokines and six targeted proteins were measured. Lipidomics analysis was conducted to identify potential lipid markers. HLJDD displayed strong efficacies, with a 61% anti-inflammatory rate at a concentration of 50 ?g/mL. The activation of TLR4/MyD88 played an essential role in the inflammatory process. All protein indexes in the HLJDD group exhibited a tendency to reverse back to normal levels. Moreover, 79 potential pathological lipid biomarkers were identified. Compared with the model group, 61 therapeutic lipid biomarkers were detected in HLJDD group. Most perturbations of lipids were ameliorated by HLJDD, mainly through the glycerophospholipid metabolic pathway. In the visual network study, the corresponding lipoproteins such as PLA2, SGMS, and SMDP were observed as important intermediates between lipid homeostasis and the TLR4/MyD88 signaling pathway.

SUBMITTER: Zhou J

PROVIDER: S-EPMC6775191 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Anti-inflammatory and Regulatory Effects of Huanglian Jiedu Decoction on Lipid Homeostasis and the TLR4/MyD88 Signaling Pathway in LPS-Induced Zebrafish.

Zhou Junyi J Gu Xinru X Fan Xiaorui X Zhou Yanyan Y Wang Hongjie H Si Nan N Yang Jian J Bian Baolin B Zhao Haiyu H

Frontiers in physiology 20190926

Huanglian Jiedu decoction (HLJDD) has been used in the clinical treatment of inflammatory conditions. To clarify the mechanism of its comprehensive anti-inflammatory activities, the correlation between lipid homeostasis and the TLR4/MyD88 signaling pathway in zebrafish was established in the present study. In the lipopolysaccharide (LPS)-induced inflammation in zebrafish model, RT-PCR assays of five inflammatory cytokines and six targeted proteins were measured. Lipidomics analysis was conducted ...[more]

PMID: 31616320

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Project description:"Shanghuo" ("excessive internal heat") is caused by exuberant endogenous fire, which does not have a comprehensive and systematic traditional Chinese medicine theory. In previous study, we had evaluated the therapeutic effect of Huanglian Jiedu Decoction (HLJDD) (granule) on patients with "Shanghuo", however, the specific mechanism was not clear, which need further exploration. To explain its intervention mechanism, we select 57 patients with oral diseases caused by "Shanghuo" and 20 health volunteers to divide into oral disease group, HLJDD intervention group and healthy control group. Firstly, biochemical indicators before and after HLJDD intervention are detected, such as inflammatory factors, oxidative stress factors and energy metabolism factors. The results exhibit that HLJDD significantly decreases indicators succinic acid (p < 0.001); tumor necrosis factor-alpha, adenosine triphosphate, citric acid (p < 0.01); interleukin-8 (IL-8), 4-hydroxynonenal, pyruvic acid, lactate dehydrogenase (p < 0.05). The levels of glucocorticoid, adrenocorticotropic hormone (p < 0.01); lactic acid, IL-4, IL-10 (p < 0.05) significantly increase after HLJDD intervention. In addition, we adopt multi-omics analysis approach to investigate the potential biomarkers. Nontargeted metabolomics demonstrate that the levels of 7 differential metabolites approach that in the healthy control group after HLJDD intervention, which are correlated with histidine metabolism, beta-alanine metabolism and sphingolipid metabolism through metabolic pathway analysis. Targeted lipidomics results and receiver operating characteristic curve analysis show that 13 differential lipids are identified in the three groups mainly focuse on lysophosphatidylcholines, lysophosphatidylethanolamines. Finally, the network associations of those differential biomarkers reveal the regulation of adenosine triphosphate and tricarboxylic acid cycle play essential role in the therapeutic effect mechanism of HLJDD in "Shanghuo". The study has laid the foundation for further revealing the mechanism and finding clinical biomarkers related to "Shanghuo".

Project description:Traditional Chinese medicine (TCM) formulas treat complex diseases through combined botanical drugs which follow specific compatibility rules to reduce toxicity and increase efficiency. "Jun, Chen, Zuo and Shi" is one of most used compatibility rules in the combination of botanical drugs. However, due to the deficiency of traditional research methods, the quantified theoretical basis of herbal compatibility including principles of "Jun, Chen, Zuo and Shi" are still unclear. Network pharmacology is a new strategy based on system biology and multi-disciplines, which can systematically and comprehensively observe the intervention of drugs on disease networks, and is especially suitable for the research of TCM in the treatment of complex diseases. In this study, we systematically decoded the "Jun, Chen, Zuo and Shi" rules of Huanglian Jiedu Decoction (HJD) in the treatment of diseases for the first time. This interpretation method considered three levels of data. The data in the first level mainly depicts the characteristics of each component in single botanical drug of HJD, include the physical and chemical properties of component, ADME properties and functional enrichment analysis of component targets. The second level data is the characterization of component-target-protein (C-T-P) network in the whole protein-protein interaction (PPI) network, mainly include the characterization of degree and key communities in C-T-P network. The third level data is the characterization of intervention propagation properties of HJD in the treatment of different complex diseases, mainly include target coverage of pathogenic genes and propagation coefficient of intervention effect between target proteins and pathogenic genes. Finally, our method was validated by metabolic data, which could be used to detect the components absorbed into blood. This research shows the scientific basis of "Jun-Chen-Zuo-Shi" from a multi-dimensional perspective, and provides a good methodological reference for the subsequent interpretation of key components and speculation mechanism of the formula.

Project description:Background:Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Methods:Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. Results:There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Conclusion:Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.

Dataset Information

Anti-inflammatory and Regulatory Effects of Huanglian Jiedu Decoction on Lipid Homeostasis and the TLR4/MyD88 Signaling Pathway in LPS-Induced Zebrafish.

Publications

Anti-inflammatory and Regulatory Effects of Huanglian Jiedu Decoction on Lipid Homeostasis and the TLR4/MyD88 Signaling Pathway in LPS-Induced Zebrafish.

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