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Effect of huanglian jiedu decoction on thoracic aorta gene expression in spontaneous hypertensive rats.

ABSTRACT: Objective. Hypertension is one of the most common cardiovascular disorders with high mortality. Here we explored the antihypertension effects of Huanglian Jiedu Decoction (HJD) on thoracic aorta gene expression in spontaneous hypertensive rats. Methods. A rat model of spontaneous hypertension was used. The gene change profile of thoracic aorta after JHD treatment was assessed by GeneChip(GC) analysis using the Agilent Whole Rat Genome Oligo Microarray. Results. Hypertension induced 441 genes upregulated and 417 genes downregulated compared with the normal control group. Treatment of HJD resulted in 76 genes downregulated and 20 genes upregulated. GC data analysis showed that the majority of change genes were involved in immune system process, developmental process, and cell death. Conclusion. Hypertension altered expression of many genes that regulate various biological functions. HJD significantly reduced hypertension and altered the gene expression profiles of SHR rats. These changing genes were involved in many cellular functions such as regulating smooth muscle contraction, Ca(2+) homeostasis, and NO pathway. This study provides the potential novel insights into hypertension and antihypertension effects of HJD.

SUBMITTER: Yue GH

PROVIDER: S-EPMC3976878 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Effect of huanglian jiedu decoction on thoracic aorta gene expression in spontaneous hypertensive rats.

Yue Gui-Hua GH Zhuo Shao-Yuan SY Xia Meng M Zhang Zhuo Z Gao Yi-Wen YW Luo Yuan Y

Evidence-based complementary and alternative medicine : eCAM 20140313

Objective. Hypertension is one of the most common cardiovascular disorders with high mortality. Here we explored the antihypertension effects of Huanglian Jiedu Decoction (HJD) on thoracic aorta gene expression in spontaneous hypertensive rats. Methods. A rat model of spontaneous hypertension was used. The gene change profile of thoracic aorta after JHD treatment was assessed by GeneChip(GC) analysis using the Agilent Whole Rat Genome Oligo Microarray. Results. Hypertension induced 441 genes upr ...[more]

PMID: 24744811

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Project description:BackgroundHuanglian 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.MethodsRetrieving 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.ResultsThere 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.ConclusionOur 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.

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:The aim of the present study was to investigate the effect of one week dehydration heat exposure on thoracic aorta reactivity in rats. Eighteen Male Sprague-Dawley rats were randomly divided into 3 groups (n=6 each group): Control group (CN), heat exposure group (HE), dehydration heat exposure group (DHE). The CN group was exposed to a room temperature of 24°C, while the HE and DHE groups were exposed to a heat temperature of 32°C. After 7 days of heat exposure, the heart rate and blood pressure of the rats were measured, and the noradrenaline (NA)-induced contraction on the aorta rings was measured by tension recording. The average contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were detected using ELISA. The expression of apoptotic genes in the thoracic aorta was measured using RT-PCR. Compared with CN, the heart rate in the HE and DHE groups had a tendency to become retarded, but there was no significant difference (P>0.05). In the HE group, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) of the rats were significantly higher than that of the CN (P<0.05). In the DHE group, the SBP of rats was significantly higher than that of the CN (P<0.05), while the SBP, DBP, and MAP of the rats were decreased compared to the rats in the HE group, although there was no statistical significance (P>0.05). In the HE and DHE groups, the NA-induced contraction on the rats thoracic aorta ring was larger than that of the CN (P<0.05), albeit there was no significant difference between the HE and DHE groups (P>0.05). The serum SOD content decreased in the HE and DHE groups, however, the reduction was significant only in the DHE group (P<0.05). The content of MDA in serum was significantly increased in the DHE group (P<0.05). The expression of BAX was significantly upregulated whereas Bcl2 expression was decreased in the DHE group (P<0.05). The results showed that a high temperature was harmful to the body, especially in the case of lack of food and water. Additionally, the heat exposure elevated blood pressure, and increased arterial reactivity, which were related to the elevated production of MDA, led to the impaired production of SOD, and an increase of cell apoptosis. These findings are useful to understand the influence of dehydrated heat exposure on the vascular function, and they provide certain theoretical and experimental guidance for protection under high temperature.

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.

Dataset Information

Effect of huanglian jiedu decoction on thoracic aorta gene expression in spontaneous hypertensive rats.

Publications

Effect of huanglian jiedu decoction on thoracic aorta gene expression in spontaneous hypertensive rats.

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