ABSTRACT
OBJECTIVE To explore the biomarkers and molecular mechanism of Huanglianjiedu decoction (HJD) on high fat diet-induced experimental atherosclerosis in rats. METHODS SD male rats were randomly dividedinto five groups(n=8):normal control group,model group,and three dosage groups (1.5, 3 and 6 g crude drug per kilogram of body weight). Atherosclerosis was induced by the combination of regular intraperitoneal injection of vitamin D3and high fat diet for 8 weeks. HJD was administered by oral gavage from the third week once per day and until the end of the study.After the final administration, the blood samples were collected for biochemical analyses [total cholesterol (TC), triglycerides (TG), highdensity lipoprotein (HDL-C), low-density cholesterol (LDL-C)] and blood gas analyses(PaO2, PaCO2, pH, ctHb, etc); the abdominal aorta sections were stained with hematoxylin and eosin for histopathology; the liver homogenate were determined for MDA, SOD, OX-LDL, MCP-1 and VCAM-1.The plasma samples were detected using ultraper formance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS).The data of endogenous compounds were preliminarily preprocessed by software Progenesis QI and then analyzed by multivari-ate statistical analysis software EZinfo 2.0 to screen the distinguished biomarkers and the metabolic pathways were analyzed through website http://www.metaboanalyst.ca/. RESULTS Compared with the normal control group,the content of TC,TG,LDL-C,PaCO2,MDA,Ox-LDL,MCP-1 and VCAM-1were significantly increased and HDL-C, PaO2, ctHb and SOD decreased in the atherosclerosis rats. HJD could significantly attenuated the high fat-induced atherosclerosis pathological injury and the above-mentioned indexes (P<0.05). The five groups could be clearly distinguished using the metabolomics method.The administration groups profile exhibited an apparent returning trend from that of the model group and that of the normal control group.Twenty-one endogenous metabolites has been significantly changed in atherosclerosis rats.HJD could remarkably up-regulate 5-L-glutamyl-taurine,L-beta-aspartyl-L-glutamic acid, histidinyl-hydroxyproline, tryptophyl-alanine, 4′-O-methyl-(-)-epicatechin, and down-regulate protoporphyrin IX,azelaic acid,lacto-N-triaose,cinnamoylglycine and 9′-carboxy-alpha-tocotri-enol. CONCLUSION The beneficial effect of HJD in high fat-induced atherosclerosis rats may be due to anti-oxidant and anti-inflammatory. And it is suggested that HJD may affect the model rats through tryptophan metabolism, taurine and hypotaurine metabolism, histidine metabolism, lysine degradation and porphyrin and chlorophyll metabolism pathway.
ABSTRACT
Objective: To investigate the variation in pharmacokinetics of berberine in the brain tissue of rats under the conditions of compound compatibility with geniposide and baicalin or the primary formula HuanglianJiedu Decoction (HJD). Methods: The rats were divided into three groups including berberine group (247.39 mg/kg), compound combination group (berberine, geniposide, and baicalin of 247.39, 130.11, and 113.01 mg/kg) and HJD group (HJD 3.92 g/kg and berberine 247.39 mg/kg). After ig administration of those compounds or formula, the brain tissues of rats were collected immediately at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 h respectively. The brain tissue was taken from the six rats in each group. A sensitive UPLC-MS method was developed for determining the concentration of berberine in the brain tissue of rats. The concentration-time curve was plotted and the pharmacokinetic parameters of rats in each group were calculated by DAS 2.0 software. Results: These results showed that the Cmax (368.59 ng/g) of berberine in rats with compound combination was increased compared with those with berberine alone (Cmax 108.01 ng/g), which is pronouncedly larger than the Cmax (31.97 ng/g) of berberine in the HJD group. Meanwhile, the AUC0-∞ of berberine in the compound combination group was 3 236.60 min∙ng/g which was much greater than the AUC0-∞ in rat brain with berberine (2 701.37 min∙ng/g) or HJD (420.34 min∙ng/g). Conclusion: The combination of geniposide and baicalin could promote the concentration of berberine, while the primary formula HJD could decrease the distribution of berberine in the brain tissue of rats.
ABSTRACT
Objective:To compare the pharmacokinetics consistence of baicalin between traditional slice decoction and dispensing granule decoction of Huanglianjiedu decoction. Methods:After the gastric administration of the two decoctions at low, middle and high dose in rats, an HPLC method was used to detect the content of baicalin in the plasma, and then DASS 2. 1. 1 software was used to cal-culate the pharmacokinetic parameters. Results:After the administration of the two decoctions at low, middle and high dose, the phar-macokinetic parameters were as follows:Cmax of 0. 25 and 0. 27μg·ml-1 ,0. 30 and 0. 31 μg·ml-1 ,0. 40 and 0. 45 μg·ml-1;AUC of 2. 48 and 2. 59μg·ml-1 ·h,3. 59 and 3. 71μg·ml-1 ·h,5. 71 and 6. 16μg·ml-1 ·h;Tmax of 3. 0 and 3. 0 h,3. 0 and 3. 0 h, 4.0 and 4.0 h;Vd of (2 822.4 ±118.2) and (2 998.9 ±255.6) L·kg-1,(3 102.6 ±176.3) and (3 405.3 ±213.8) L·kg-1, (4 231.2 ±155.4) and (4 486.0 ±187.0) L·kg-1;CL of (2 923.3 ±215.6) and (2 767.5 ±184.6)L·h-1·kg-1,(4 921.7 ± 225.4) and (4 040.8 ±246.7)L·h-1·kg-1,(5 255.9 ±189.7) and (4 868.7 ±260.4)L·h-1·kg-1;and t1/2 of (3.88 ± 0.41) and (3.71 ±0.37)h,(4.19 ±0.36) and (3.73 ±0.51)h, (5.54 ±0.38) and (5.80 ±0.54)h. Conclusion: The pharma-cokinetic parameters of baicalin have no significant difference between traditional slice decoction and dispensing granule decoction of Huanglianjiedu decoction.
ABSTRACT
Objective To analysis the effective ingredients in Huanglianjiedu decoction under different decocting conditions. Methods The detecting method of HPLC was established and the ingredients in Huanglianjiedu decoction under different decocting time and times were analyzed. Result Water- soluble glycoside of gardenoside and baicalin reached balance of dissolution within 20 min and their dissolution rate were about 82% and 60% respectively. Water-soluble alkaloids of berberine and palmatine reached balance of dissolution within 30 min and their dissolution rate were about 45%. The dissolution rate of wogonin was 31% at 60 min. The dissolution rate of Crocin-Ⅰ reached top at 20 min and fell down after 20 min. Decocting times for fat-soluble constitutes was more important than water-soluble constitutes. Conclusion The decocting condition has effect on the dissolution rate and stability of the ingredients in Huanglianjiedu decoction. The decocting condition is very important to the quality control of decoction.
ABSTRACT
[Objective] To find the method of pharmacokinetics experiment about Huanglianjiedu Decoction.[Methods] According to references about pharmacokinetics experiments on Huanglianjiedu Decoction,the article summarized the achievements in quantitative analysis,the influence of distill techniques and pharmacokinetics on indict components in Huanglianjiedu Decoction.This article attached importance to applying the technologies of PK-PD modeling and Data Mining in research of Chinese traditional medicine compound.[Conclusion] The pharmacokinetics study on Huanglianjiedu Decoction is just in the first step; thereby further studies will be taken on this decoction in order to reveal the active fractions and effect mechanism.
ABSTRACT
Objective: To study the content of alkaloids in Huanglianjiedu Decoction and its disassemble prescription. Methods: The contents of four alkaloids such as berberine, jatrorrhizine, coptisine, palmatine in Huanglian jiedu Decoction and its disassemble prescription were determined by HPLC. Results: The content of four alkaloids extracted by tranditional decoction had a tendency to low. On the coutrary, when Rhizoma Coptis and Cortex Phellodendri were decocted together the quantity of alkaloids was additive, and when two herbs above decocted with Radix Scutella and Fructus Gardeniae the quantity of alkaloids decreased obviously. Conclusion:This study can provide a basis for establishing rational quanlitative standard for Huanglianjiedu Decoction.
ABSTRACT
Objective:To identify Huanglianjiedu Decoction preparation (Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, Fructus Gardeniae) made from different technics and Japanese Kampo with fingerprint chromatographic. Methods: The HPLC method was used, chromatography conditions were C 18V column, binary solvent-delivery gradient elution, diode-array detector, internal standard (paeoniflorin) were taken as the criteria for quality control. Results: The result showed that 15～16 characteristic peaks were common, but the new technic preparation and EtOH extract showed a specific characteristic peak. And significant deviation has been found from peak-height ratio of characteristic peaks to internal standard in various preparations, which were made from different technics or from different materials. Conclusion: The good reproducibility and stability are showed in experiment results. The HPLC fingerprint can be used for identifying this traditional Chinese medicine preparations which were made from different technics or from different materials.