Effects Of Huanglian Jiedu Decoction Research Articles

Huanglian Jiedu decoction alleviates ischemia-induced cerebral injury in rats by mitigating NET formation and activiting GABAergic synapses.

Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on ischemic stroke have yet to be elucidated. The aim of this study is to elucidate the underlying pharmacological mechanisms of HLJD based on the inhibition of neuroinflammation and the amelioration of nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats and received HLJD treatment. Effects of HLJD on neurological function was assessed based on Bederson's score, postural reflex test and asymmetry score. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, Hematein and eosin (HE) and Nissl staining were used to observe the pathological changes in brain. Then, transcriptomics was used to screen the differential genes in brain tissue in MCAO/R model rats following HLJD intervention. Subsequently, the effects of HLJD on neutrophil extracellular trap (NET) formation-related neuroinflammation, gamma-aminobutyric acid (GABA)ergic synapse activation, nerve cell damage and proliferation were validated using immunofluorescence, western blot and enzyme-linked immunosorbent assay (ELISA). Our results showed that HLJD intervention reduced the Bederson's score, postural reflex test score and asymmetry score in MCAO/R model rats. Pathological staining indicated that HLJD treatment decreased the cerebral infarction area, mitigated neuronal damage and increased the numbers of Nissl bodies. Transcriptomics suggested that HLJD affected 435 genes in MCAO/R rats. Among them, several genes involving in NET formation and GABAergic synapses pathways were dysregulated. Subsequent experimental validation showed that HLJD reduced the MPO+CitH3+ positive expression area, reduced the protein expression of PAD4, p-P38/P38, p-ERK/ERK and decreased the levels of IL-1β, IL-6 and TNF-α, reversed the increase of Iba1+TLR4+, Iba1+p65+ and Iba1+NLRP3+ positive expression area in brain. Moreover, HLJD increased GABA levels, elevated the protein expression of GABRG1 and GAT3, decreased the TUNEL positive expression area and increased the Ki67 positive expression area in brain. HLJD intervention exerts a multifaceted positive impact on ischemia-induced cerebral injury in MCAO/R rats. This intervention effectively inhibits neuroinflammation by mitigating NET formation, and concurrently improves nerve cell damage and fosters nerve cell proliferation through activating GABAergic synapses.

Effect of Huanglian Jiedu Decoction on cardiac endoplasmic reticulum stress in spontaneously hypertensive rats

Effect of Huanglian Jiedu Decoction on cardiac endoplasmic reticulum stress in spontaneously hypertensive rats

Unraveling the treatment effects of huanglian jiedu decoction on drug-induced liver injury based on network pharmacology, molecular docking and experimental validation

Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.

Metabolomics and lipidomics combined with serum pharmacochemistry uncover the potential mechanism of Huang-Lian-Jie-Du decoction alleviates atherosclerosis in ApoE−/− mice

Ethnopharmacological relevanceAtherosclerosis (AS) is one of the main cardiovascular diseases (CVDs) leading to an increase in global mortality, and its key pathological features are lipid accumulation and oxidative stress. Huang-Lian-Jie-Du decoction (HLJDD), a representative formula for clearing heat and detoxifying, has been shown to reduce aortic lipid plaque and improve AS. However, multiple components and multiple targets of HLJDD pose a challenge in comprehending its comprehensive mechanism in the treatment of AS. Aim of the studyThis study was designed to illustrate the anti-AS mechanisms of HLJDD in an apolipoprotein E-deficient (ApoE−/−) mouse model from a metabolic perspective. Materials and methodsApoE−/− mice were kept on a high-fat diet (HFD) to induce AS. Serum total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were determined to evaluate the influence of HLJDD on dyslipidemia. Oil red O was used to stain mouse aortic lipid plaques, and hematoxylin and eosin (HE) staining was used to assess the pathological changes in the aortic roots. Metabolomics and lipidomics combined with serum pharmacochemistry were performed to research the HLJDD mechanism of alleviating AS. ResultsIn this study, HLJDD treatment improved serum biochemical levels and histopathological conditions in AS mice. A total of 6 metabolic pathways (arginine biosynthesis, glycerophospholipid, sphingolipid, arachidonic acid, linoleic acid, and glycerolipid metabolism) related to 25 metabolic biomarkers and 41 lipid biomarkers were clarified, and 22 prototype components migrating to blood were identified after oral administration of HLJDD. ConclusionHLJDD improved AS induced by HFD in ApoE−/− mice. The effects of HLJDD were mainly attributed to regulating lipid metabolism by regulating the metabolic pathways of glycerophospholipids, sphingolipids, arachidonic acid, linoleic acid, and glycerolipids and reducing the levels of oxidative stress by upregulating arginine biosynthesis.

The effect of Huanglian Jiedu Decoction on inflammatory factors and oxidative stress in patients with acute ischemic stroke

The effect of Huanglian Jiedu Decoction on inflammatory factors and oxidative stress in patients with acute ischemic stroke

Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study.

Corona virus disease 2019 (COVID-19) is prone to induce multiple organ damage. The kidney is one of the target organs of SARS-CoV-2, which is susceptible to inducing acute kidney injury (AKI). Huanglian Jiedu Decoction (HLJDD) is one of the recommended prescriptions for COVID-19 with severe complications. We used network pharmacology and molecular docking to explore the therapeutic and protective effects of HLJDD on COVID-19-associated AKI. Potential targets related to "HLJDD," "COVID-19," and "Acute Kidney Injury/Acute Renal Failure" were identified from several databases. A protein-protein interaction (PPI) network was constructed and screened the core targets according to the degree value. The target genes were then enriched using gene ontology and Kyoto Encyclopedia of Genes and Genomes. The bioactive components were docked with the core targets. A total of 65 active compounds, 85 common targets for diseases and drugs were obtained; PPI network analysis showed that the core protein mainly involved JUN, RELA, and AKT1; functional analysis showed that these target genes were mainly involved in lipid and atherosclerosis signaling pathway and IL-17 signal pathway. The results of molecular docking showed that JUN, RELA, and AKT1 had good binding activity with the effective chemical components of HLJDD. In conclusion, HLJDD can be used as a potential therapeutic drug for COVID-19-associated AKI.

Huanglian Jiedu Decoction in the Treatment of the Traditional Chinese Medicine Syndrome "Shanghuo"-An Intervention Study.

“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”.

Integrating Network Pharmacology and Experimental Validation to Decipher the Mechanism of Action of Huanglian Jiedu Decoction in Treating Atherosclerosis.

BackgroundThis study used network pharmacology, molecular docking and experimental validation to assess the effects of Huanglian Jiedu Decoction (HLJDD) on atherosclerosis (AS).MethodsThe components and targets of HLJDD were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and information on the genes associated with AS was retrieved from the GeneCards and OMIM platforms. Protein–protein interactions were analyzed using the STRING platform. A component–target–disease network was constructed using Cytoscape. GO and KEGG analyses were performed to identify molecular biological processes and signaling pathways, and the predictions were verified experimentally. Molecular docking was conducted with ChemOffice software, PyMOL software and Vina to verify the correlation of targets and compounds.ResultsHLJDD contained 31 active compounds, with quercetin, kaempferol, moupinamide and 5-hydroxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chromone as the core compounds. The most important biotargets of HLJDD in AS were ICAM-1, CD31 and RAM-11. The molecular docking results showed that the molecular docking interaction energy between the 3 key targets and the 4 high-degree components were much less than −5 kJ∙mol−1. The experimental validation results showed that HLJDD might treat AS mainly by reducing TC, TG and LDL-C and increasing HDL-C, upregulating CD31 expression, reducing ICAM-1 and RAM-11 expression, and downregulating inflammatory factors, including CRP, IL-6 and TNF-α. These results support the network pharmacology data and demonstrate that HLJDD affects the expression of core genes and alters the leukocyte transendothelial migration signaling pathway.ConclusionBased on network pharmacology and experimental validation, our study indicated that HLJDD exerted anti-AS effect through upregulating CD31 expression and reducing the expression of ICAM-1 and RAM-11. HLJDD may be a potential therapeutic drug to the prevention of AS.

Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P&lt;0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P&lt;0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P&lt;0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P&lt;0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Untargeted metabolomics and lipidomics uncovering the cardioprotective effects of Huanglian Jiedu Decoction on pathological cardiac hypertrophy and remodeling

Ethnopharmacological relevanceAs a classic herbal prescription, Huanglian Jiedu Decoction (HLJDD) exhibits positive effects against cardiac dysfunction. However, its cardioprotective effects and potential mechanism(s) of action still need to be systematically investigated. Aim of the studyThis study aimed to reveal the underlying therapeutic mechanism of HLJDD on transverse aortic constriction (TAC)-induced pathological cardiac hypertrophy and remodeling. Materials and methodsTAC-induced cardiac hypertrophy and remodeling mice model was established to evaluate the therapeutic effects of HLJDD. Serum untargeted metabolomics and lipidomic profiling were performed using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry coupled with multivariate statistical analyses. ResultsOral administration of HLJDD (2.5 g/kg/day, 5.0 g/kg/day) significantly improved the heart morphology, enhanced the heart function, and alleviated the accumulation of fibrosis in the interstitial space and the infiltration of inflammatory cells in TAC-stimulated mice. Serum untargeted metabolomics analysis showed that significant alterations were observed in metabolic signatures between the TAC-model and sham group. Principal component analysis and orthogonal partial least-squares discriminant analysis screened 59 differential metabolic features and 13 metabolites were identified. The disturbed metabolic pathways in TAC group mainly related to lipid metabolism. Further serum lipidomic profiling showed that most lipids including cholesterol esters, ceramides, glycerides, fatty acids and phospholipids were decreased in TAC group and these alterations were reversed after HLJDD intervention. ConclusionHLJDD alleviates TAC-induced pathological cardiac hypertrophy and remodeling, and its potential therapeutic mechanism involves the regulation of lipid metabolism.

Huanglian Jiedu Decoction ameliorates DSS-induced colitis in mice via the JAK2/STAT3 signalling pathway

BackgroundUlcerative colitis (UC) is an intestinal disease which was characterized by intestinal inflammation, mucosal injury and fibrosis. In this paper, the effect of Huanglian Jiedu Decoction (HJD), a well-known traditional Chinese medicine with significant anti-inflammatory effect, on dextran sulphate sodium (DSS)-induced UC in mice and inhibition of JAK2/STAT3 pathway were investigated.MethodsBALB/c mice were randomly divided into 6 groups: HJD group (high, medium and low dose), USAN group, UC group, and control group. UC in mice were induced through free access to 3% DSS solution. After being treated with HJD for 8 days, all animals were sacrifice. Pathological examination of colonic specimen was performed by H&E staining. Cytokines (TNF-α, IL-6, and IL-1β) in colon were assayed by ELISA and immunofluorescence, MPO in colon and ATT in serum were detected by ELISA. Moreover, mice in HJD group and UC group were treated with AG490 to inhibit the expression of JAK2 protein, then the expression of JAK2 and STAT3 protein in colon was determined by western blotting and immunofluorescence staining. Furthermore, KI67 in colon was examined by immunohistochemistry, and apoptosis was detected by TUNEL staining, and collagen deposition was assayed by Masson staining after JAK2/STAT3 pathway in UC mice was inhibited by HJD.ResultsAfter mice being treated with HJD, the symptoms (weight loss and haematochezia) of UC were alleviated, and the contents of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and MPO in colon were significantly decreased. The expression of JAK2 and STAT3 protein was reduced after administration with HJD. After JAK2/STAT3 pathway being inhibited with HJD, the cell apoptosis, collagen deposition and immunoreactivity of macrophage in colon were significantly reduced, but the expression of Ki67 was markedly enhanced in both UC group and HJD group compare with control group.ConclusionsHJD treatment can alleviate intestinal mucosal damage and has the protective effect on UC by downregulating JAK2 and STAT3 expression to reduce inflammation via JAK2/STAT3 pathway.

Ancient Chinese Medicine Herbal Formula Huanglian Jiedu Decoction as a Neoadjuvant Treatment of Chemotherapy by Improving Diarrhea and Tumor Response.

BackgroundDiarrhea is a major gastrointestinal complication in cancer patients receiving chemotherapy. Prognosis and treatment of chemotherapy-induced diarrhea (CID) remain unsatisfactory. This study aims to explore the potential of an ancient Chinese Medicine herbal formula Huanglian Jiedu Decoction (HLJDD) as an adjuvant treatment on CID.MethodHLJDD extract was prepared by GMP manufacturing standard with quality and stability being checked. 5-fluorouracil (5-Fu) and irinotecan (CPT-11)-induced diarrhea model in mice was established and pre-, co- and post-treatment of HLJDD was implemented. Mechanism of action was explored by detecting related protein expression. In addition, the effect of HLJDD on diarrhea and tumor response induced by clinical regimens FOLFOX and FOLFIRI was measured in murine orthotopic colorectal cancer model.ResultsHLJDD exhibited consistency in quality and stability after 24-month storage. Pre-treatment of HLJDD, but not co-treatment or post-treatment, could significantly improve the diarrhea score, body weight loss and intestinal damage in 5-Fu- and CPT-11-treated mice. Pre-treatment of HLJDD reduced cell apoptosis in the intestine of chemotherapy-treated mice, and promoted renewal of intestinal cell wall. CD44 was predicted as the potential target of HLJDD-containing compounds in CID. HLJDD pre-treatment induced presentation of CD44-postive cells in the intestine of chemotherapy-treated mice, and initiated expression of stemness-associated genes. Transcriptional products of the downstream Wnt signaling of CD44 were elevated. Furthermore, pre-treatment of HLJDD could significantly improve the tumor response of clinical chemotherapy regimens FOLFOX and FOLFIRI in orthotopic colorectal cancer, and reduce diarrhea and intestinal damage. Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response.

Study on the Effect of Huanglian Jiedu Decoction on the Composition of Gut Microflora in SD Rats Based on 16S rRNA Sequencing.

Objective To study the effects of Huanglian Jiedu Decoction (HJD) on gut microflora of SD rats. Method After 3 days of adaptive feeding, 36 rats were randomly divided into 4 groups, namely, the normal control group (NC, 10 mL/kg, distilled water), high_HJD dose group (H_HJD, 6.25 g/kg, weight ratio between crude drug and rat), medium_HJD dose group (M_HJD, 3.125 g/kg), and low_HJD dose group (L_HJD, 1.56 g/kg), and each group consisted of 9 mice. The HJD groups were then treated with orally administered HJD for 21 days, while the NC group was treated with distilled water. After 7 days, 14 days, and 21 days of the experiment and after 12 hours of fasting and water deprivation, 3 SD rats in each group were randomly sacrificed by cervical dislocation and sterile operation to collect stool faces. Sample DNA was extracted by Fecal total DNA extraction kit, sequenced using Illumina MiSeq platform, and analyzed. Results The abundance of Romboutsia, Turicibacter, Lactobacillus, and Gemella decreased, while that of Escherichia_Shigella, Coprobacillus, Blautia, Akkermansia, Klebsiella, Rhodococcus, Parabacteroides, Citrobacter, Enterococcus, Bacteroides, and Erysipelotrichaceae_incertae_sedis increased after using H_HJD. The abundance of Gemella, Turicibacter, Romboutsia, and Lactobacillus decreased, while that of Blautia, Akkermansia, Escherichia_Shigella, Thiobacillus, Rothia, Enterococcus, Lactobacillus, and Erysipelotrichaceae-incertae-sedis increased after using M_HJD. The abundance of Romboutsia, Turicibacter, Lactobacillus, and Gemella decreased, while that of Escherichia_Shigella, Bacteroides, Akkermansia, Enterococcus, Rhodococcus, Parabacteroides, Desulfovibrio, Blautia, Fusobacterium, Rothia, and Streptococcus increased after using L_HJD. Conclusion HJD can regulate gut microbiota, and its effect varies with different dosage and duration of medication.

Huang-Lian-Jie-Du Decoction Ameliorates Acute Ulcerative Colitis in Mice via Regulating NF-κB and Nrf2 Signaling Pathways and Enhancing Intestinal Barrier Function.

Evidence shows that intestinal inflammation, oxidative stress, and injury of mucosal barrier are closely related to the pathogenesis of ulcerative colitis (UC). Huang-lian-Jie-du Decoction (HLJDD) is a well-known prescription of traditional Chinese medicine with anti-inflammatory and antioxidative activities, which may be used to treat UC. However, its therapeutic effect and mechanism are still unclear. In this study, the UC model of BABL/c mice were established by DSS [3.5% (w/v)], and HLJDD was given orally for treatment at the same time. During the experiment, the clinical symptoms of mice were scored by disease activity index (DAI). Besides, the effects of HLJDD on immune function, oxidative stress, colon NF-κB and Nrf2 signaling pathway, and intestinal mucosal barrier function in UC mice were also investigated. The results showed that HLJDD could alleviate body weight loss and DAI score of UC mice, inhibit colonic shortening and relieve colonic pathological damage, and reduce plasma and colon MPO levels. In addition, HLJDD treatment significantly up-regulated plasma IL-10, down-regulated TNF-α and IL-1β levels, and inhibited the expression of NF-κB p65, p-IκKα/β, and p-IκBα proteins in the colon. Moreover, NO and MDA levels in colon tissues were significantly reduced after HLJDD treatment, while GSH, SOD levels and Nrf2, Keap1 protein expression levels were remarkably elevated. Additionally, HLJDD also protected intestinal mucosa by increasing the secretion of mucin and the expression of ZO-1 and occludin in colonic mucosa. These results indicate that HLJDD could effectively alleviate DSS-induced mice UC by suppressing NF-κB signaling pathway, activating Nrf2 signaling pathway, and enhancing intestinal barrier function.

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

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 μg/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.

Effect of Huanglian Jiedu Decoction on vascular endothelium factor and expression of RhoA protein factor in young spontaneously hypertensive rats

Effect of Huanglian Jiedu Decoction on vascular endothelium factor and expression of RhoA protein factor in young spontaneously hypertensive rats

English

This study aimed to investigate the antifebrile and anti-inflammatory effect of Huanglian Jiedu Decoction (HLJDD). The rabbits received intravenous injection of lipopolysaccharide (LPS) after orally administered with HLJDD and the rectal temperatures of rabbits were monitored. The concentrations of interleukin-1 beta (IL-1&beta;) and tumor necrosis factor alpha (TNF-&alpha;) in serum were assayed using rabbit IL-1&beta; and TNF-&alpha; enzyme-linked immunosorbent assay (ELISA) kits. Carrageenan-induced paw edema in rats and the anti-inflammatory effects of HLJDD were also explored. HLJDD treatment group resulted in a significant fall in body temperature in biphasic fever peak (p &lt; 0.05), and there were no significant differences between HLJDD treatment group and Ibuprofen (IBR) treatment group in biphasic fever peak at time 1 and 3 h (p &gt; 0.05). HLJDD treatment group reduced the concentrations of IL-1&beta; in serum at time 1 and 3 h to control febrile responses. Moreover, paw edema of carrageenan-treated rats were significantly attenuated in rats pretreated with HLJDD. Mechanistic studies showed that HLJDD effectively decreased expressions of COX-2 and inducible nitric oxide synthase (iNOS) proteins. These results suggested that HLJDD would be a valuable candidate for further investigation as a new anti-arthritic drug. Key words: Lipopolysaccharide, Huanglian Jiedu Decoction (HLJDD), anti-inflammatory, interleukin-1 beta, tumor necrosis factor alpha.

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

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.

Effects of Chinese herbal medicine Huanglian Jiedu Decoction on urine metabonomics of healthy people

To study biomarkers and their diversification in healthy people's urine before and after oral administration of Huanglian Jiedu Decoction, a compound Chinese herbal medicine, and to investigate the influence of Huanglian Jiedu Decoction on urine metabonomics of healthy people. Ten healthy volunteers joined in this experiment and signed informed consent. They were given oral administration of Huanglian Jiedu Decoction for 3 days, and their urine was collected every morning. The samples were centrifuged at 13 000×g for 10 min at 4 degrees centigrade, and the supernatant was stored at -75 degrees centigrade. The samples were examined by a core technology called ultra-performance liquid chromatography quadruple time of flight/mass spectrometry and then the data were analyzed by principal components analysis and partial least square-discriminant analysis to investigate trajectory diversification and corresponding relations of the time and amount of urine metabonomics before and after oral administration of Huanglian Jiedu Decoction. Evident variance of urine metabonomics took place after oral administration of Huanglian Jiedu Decoction, which showed that the metabolism of healthy people had been visibly affected. Seven potential biomarkers which play a role in healthy people on behalf of Huanglian Jiedu Decoction were preliminarily found, and one biomarker which had biological significance was identified as 2-(formylamino)-benzoic acid. The effects of Huanglian Jiedu Decoction on urine metabonomics in healthy people investigated at the level of metabolism can provide theoretical and technical support for the study of Huanglian Jiedu Decoction's influence on heat syndrome.

Effects of Huanglian Jiedu Decoction on blood lipid metabolism and its related gene expressions in rats with hyperlipidemia

To observe the effects of Huanglian Jiedu Decoction (HJD), a compound traditional Chinese herbal medicine, on lipid metabolism and its related gene expressions in rats with hyperlipidemia. Fifty SD rats were randomly divided into normal control group, untreated group, Lipitor (atorvastatin) group, and low- and high-dose HJD groups. Except the normal control group, rats in the other groups were fed with high-fat diet to induce hyperlipidemia. Then the rats were administered with corresponding drugs for 8 weeks. After treatment, the serum levels of total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assayed. The activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in liver tissues were measured. Low-density lipoprotein receptor (LDLR) and peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA expressions in liver tissues were determined by reverse transcription-polymerase chain reaction. Compared with the normal control group, the levels of serum TC, TAG and LDL-C in the untreated group were increased and the level of serum HDL-C was reduced. The activities of LPL and HL and expressions of LDLR and PPARgamma mRNAs in the untreated group were lower than those in the normal control group. After treatment, high-dose HJD significantly improved hyperlipemia by decreasing TC, TAG and LDL-C and increasing HDL-C. The activities of LPL and HL and expression levels of LDLR and PPARgamma mRNAs in liver tissues were also markedly enhanced in the high-dose HJD group as compared with those in the untreated group. HJD can activate the activity of lipid metabolism enzyme, and enhance the expressions of LDLR and PPARgamma mRNAs to modulate the lipid metabolic disorders in rats with hyperlipidemia.