Quality evaluation of Hugan Tablets based on HPLC fingerprint and chemical pattern recognition / 中草药

Objective: To establish the HPLC fingerprint of Hugan Tablets and provide a scientific basis for the quality control of Hugan Tablets. Methods: HPLC method was adopted and using schizandrin as reference, and 10 batches of Hugan Tablets were determined. Similarity evaluation was performed by using Similarity Evaluation System for Fingerprint Chromatogram of TCM (2004A) to confirm the common peak. Pattern recognition analysis was performed using principal component analysis (PCA) and orthogonal partial least squares-discrimination analysis (OPLS-DA). Results: There were 22 common peaks in HPLC of 10 batches of samples. Schizandrin, saikosaponin a, saikosaponin c, saikosaponin d, schisandrin A, and schizandrin B were identified by chemical identification of the reference substance. The similarity of 10 batches of samples was higher than 0.97, which indicated that the overall quality of the drug was relatively stable. However, there were slight differences between the quality of different batches of drugs found by PCA, and they were mainly divided into two categories. Finally, OPLS-DA was used to screen out two main components that caused the quality differences in the batches, namely peak 12 (saikosaponin D) and peak 22. Conclusion: The construction of fingerprint of Hugan Tablets and chemical pattern recognition provides a practical and theoretical basis for the quality evaluation of Hugan Tablets, which can provide a scientific basis for manufacturers to control drug quality more efficiently and reasonably in drug production.

Expert consensus statement on Hugan Tablets in clinical practice / 中国中药杂志

Hugan Tablets is a Chinese patent medicine,it has the function of anti-inflammation and reducing transaminase. Based on questionnaire investigation of doctors and a systematic review of research literature on Hugan Tablets,using international clinical practice guidelines' developing methods,with the best available evidence and fully combining expert experience,and following the principle of " evidence-based,consensus-based and experience-based",Expert consensus statement on Hugan Tablets in clinical practice was developed by more than 30 multidisciplinary experts from the nationwide,aimed at guiding and standardizing the rational use of Hugan Tablets by clinicians and to improve clinical efficacy and safety. The expert consensus adopts internationally recognized recommendation criteria for classification of evidence: GRADE. The formation of expert consensus adopts the nominal group technique. Six main considerations are quality of evidence,curative effect,safety,economical efficiency,patient acceptability and other factors. If there is sufficient evidence,a " recommendation" is formed,using GRADE grid voting rule. If there isn' t sufficient evidence,a " consensus opinion" is formed,using majority counting rule. Focus on the indication,usage and dosage,drug use in special population and safety of Hugan Tablets,two recommendations and eight consensus opinions were put forward. Through expert meetings and correspondence,a nationwide consultation and peer review was conducted. This consensus applies to clinicians in hospitals and grass-roots health services,to provide guidance and reference for the rational use of Hugan Tablets.

"Multi-component-multi-target-multi-pathway" mechanism of Kuihua Hugan Tablets based on network pharmacology / 中国中药杂志

To predict the targets of active ingredients of Kuihua Hugan Tablets by network pharmacology, and explore the "multi-component-multi-target-multi-pathway" hepatoprotective mechanism of action. First, through traditional Chinese medicine systems pharmacology(TCMSP) and TCM Database@Taiwan Database, main active ingredients of Kuihua Hugan Tablets were screened out based on oral bioavailability(OB), drug-likeness(DL) and effective half-lives(HL). The targets of active ingredients of Kuihua Hugan Tablets were predicted based on the PharmMapper method. Then, the prediction was conducted by screening the target genes associated with chronic hepatitis and early cirrhosis through CooLGeN and GeneCards databases. Target gene functions and signal pathways were analyzed by bioinformatics annotation database Metascape. Cytoscape software was used to construct the Kuihua Hugan Tablets ingredient-target and ingredient-target-pathway network. String database combined with Cytoscape software was used to construct the networks of component-target and component-target-pathway. STRING database was combined with Cytoscape software to draw protein-protein interaction(PPI) network and conduct network topology analysis. Finally, Systems Dock Web Site software was applied in verifying the molecular docking between active ingredients and potential protein targets. A total of 26 compounds and 509 potential targets were screened out from Kuihua Hugan Tablets in the experiment. The results of PPI network analysis indicated that albumin(ALB), insulin-like growth factor 1(IGF1), matrix metalloproteinase-9(MMP9), matrix metalloproteinase-2(MMP2), non-receptor tyrosine kinase proto-oncogene(SRC), estrogen receptor 1(ESR1) and cancer-signal transduction-inflammation-drugs metabolism-related biological processes and metabolic pathways were closely associated with the active ingredients in Kuihua Hugan Tablets. The effects of Kuihua Hugan Tablets in alleviating chronic hepatitis and early cirrhosis indicated the multi-component, multi-target, and multi-pathway characteristics of traditional Chinese medicines, providing new ideas for further research and development of Kuihua Hugan Tablets.

Pretreatment Conditions in the Detection of Selenium from Hugan Tablets by Central Composite Design-Response Surface Methodology / 医药导报

Objective To optimize the pretreatment conditions in the detection of selenium from hugan tablets. Methods The main influential factors of pretreatment conditions included concentration of hydrochloric acid,time in water bath and concentration of potassium ferricyanide solution.The extraction effect was evaluated with the content of selenium.Pretreatment conditions were optimized by central composite design-response surface methodology. Results The best pretreatment conditions was 6 mol·L-1hydrochloric acid,30 minutes of bathing in water bath,20%potassium ferricyanide solution. Conclusion The central composite design-response surface methodology is highly predictive,reasonable and feasible.

Metabonomic analysis of Hugan Tablets on CCl4-induced acute hepatic injury in rats based on 1 H-NMR / 中国药理学通报

Aim To identify the potential biomarkers associated with carbon tetrachloride(CCl 4 )-induced a-cute hepatic injury in rats and explore the therapeutic effect of Hugan Tablets(HGT). Methods The model was established by intraperitoneal injection of CCl4 in oil(1 : 1,V/ V)with a dosage of 1 mL·kg - 1 body weight to rats once. The levels of aspartate aminotrans-ferase(AST),alanine aminotransferase(ALT),alka-line phosphatase (ALP ) and lactate dehydrogenase (LDH)in serum of rats were determined. Moreover,a proton nuclear magnetic resonance (1 H-NMR)based metabonomic approach in combination with multivariate data analysis was applied to demonstrate CCl4-induced acute hepatic injury metabolic perturbations in rat urine and feces and identify the corresponding metabolic bio-markers. The intervention effect of HGT was evaluated based on the changes of metabolic phenotype and po-tential biomarkers related to acute hepatic injury. Re-sults The levels of AST,ALT,ALP and LDH in ser-um of rats with acute hepatic injury were significantly reduced by administration of HGT,respectively. The disturbed metabolic state associated with CCl4-induced acute hepatic injury in rat urine and feces could be re-stored by HGT. Meanwhile,five potential biomarkers (2-oxoglutarate,citrate,creatinine,trimethylamine N-oxide,hippurate)in rat urine and three potential bio-markers(butyrate,glucose,uracil)in rat feces related to acute hepatic injury were reversed by administration of HGT,respectively. Conclusion HGT exerts pro-tective effects against CCl4-induced acute hepatic inju-ry in rats,which is probably mediated by regulation of tricarboxylic acid cycle and gut microbiota metabolism.

Study on the Hepatoprotective Effects of Hugan Tablets Based on Serum and Liver Metabonomics / 中国药房

OBJECTIVE:To elucidate the efficacy and mechanism of Hugan tablets in hepatoprotective effects from perspective of metabolic pathways. METHODS:36 male rats were randomly divided into normal group (0.5%sodium carboxymethyl cellu-lose),model group(0.5%sodium carboxymethyl cellulose)and Hugan tablets group(1.7 g/kg),12 in each group,intragastrically administrated once a day,for 9 d. After 1 h of last administration,rats in model group and Hugan tablets group were intraperitone-ally injected 50%CCl4 peanut oil solution 1 mL/kg to induce liver injury. After 24 h of modeling,malondialdehyde(MDA),super-oxide dismutase(SOD),glutathione peroxidase(GSH-Px)levels in liver tissue of rats were detected. Nuclear magnetic resonance spectroscopy(1H-NMR)metabolomics technique was adopted to establish the serum and liver metabolite profiles of rats,and the ef-fects of Hugan tablets on changes of metabolic profile and potential biomarkers in serum and liver of rats with CCl4-induced acute liver injury were analyzed. RESULTS:Compared with normal group,MDA level in liver tissue of rats in model group was signifi-cantly increased(P<0.05),SOD and GSH-Px levels were significantly reduced(P<0.05). Both body physiology and material me-tabolism of rats were obviously changed,and levels of 11 metabolic potential biomarkers in serum and 14 metabolic potential bio-markers in liver were significantly increased/decreased (P<0.05). Compared with model group,MDA level in liver tissue in Hugan tablets group was significantly reduced(P<0.05),SOD and GSH-Px levels were significantly increased(P<0.05). Serum and liver metabolism tended to be normal,6 metabolic potential biomarkers(isoleucine,leucine,3-hydroxybutyrate,acetone,ace-toacetate,choline) in serum and 8 metabolic potential biomarkers (3-hydroxybutyrate,alanine,glutamate,pyruvate,succinate, choline,lactate,glucose)in liver got significant callback(P<0.05). CONCLUSIONS:The hepatoprotective mechanism of Hugan tablets may be associated with antioxidative stress and regula-tion of lipid metabolism,glucose metabolism and amino acid metabolism.

Simultaneous Determination of Five Effective Components in Hugan Tablets by HPLC / 中国药师

Objective:To establish an HPLC method for the simultaneous determination of adenosine, schisandrin, schisantherin,deoxyschizandrin and schisandrin B in Hugan tablets. Methods:An Agilent Eclipse XDB column(250 mm × 4. 6 mm,5 μm)was used with the mobile phase of acetonitrile- 0. 7% phosphoric acid solution with gradient elution. The flow rate was 0. 80 ml·min -1 . The detection wavelength was set at 260 nm in 0-14 min and 250 nm in 14-58 min,the column temperature was 30℃ ,and the sample size was 10 μl. Results:There was a good linear relationship within the range of 2. 35- 47. 00 μg· ml -1(r = 0. 999 8)for adenosine,14. 90-297. 00 μg·ml -1(r = 1. 000 0)for schisandrin,3. 46- 69. 20 μg·ml-1(r = 0. 999 9)for schisantherin,4. 00- 80. 10 μg·ml -1(r = 1. 000 0)for deoxyschizandrin and 3. 42- 68. 30 μg·ml-1(r = 0. 999 9)for schisandrin B. The average recoveries for the five components were all above 98% . Conclusion:The method is simple and accurate with good reproducibility,which can be used for the determination of adenosine,schisandrin,schisantherin,deoxyschizandrin and schisandrin B in Hugan tablets.

Efficacy Observation of Polyene Phosphatidyl Choline Combined with Hugan Tablets in the Treatment of Drug-induced Liver Injury / 中国药师

Objective:To observe the efficacy of polyene phosphatidyl choline combined with Hugan tablets in the treatment of drug-induced liver injury. Methods:Totally 80 cases of drug-induced liver injury were randomly divided into the observation group (40 cases )and the control group(40 cases). The observation group was given polyene phosphatidyl choline injections 697. 5mg+5%glucose injections 250ml,ivd,qd,combined with Hugan tablets 1. 44g,po,tid,the control group was given polyene phosphatidyl choline injections 697. 5mg+5%glucose injections 250ml,ivd,qd,and the symptomatic treatment in the two groups was the same. The two groups were treated for 20d. Alanine aminotransferase ( ALT), aspartate aminotransferase ( AST), total bilirubin ( TBIL), glutamyl transpeptidase(GGT) and alkaline phosphatase(ALP)were detected respectively before and after the treatment, and the therapeutic effects were compared between the two groups. Results: After the treatment,the total effective rate in the observation group was 97. 5%,which was significantly higher than that in the control group(P <0. 01),Symptoms,signs and biochemical indices in the two groups were improved obviously. The decrease of ALT,AST and GGT in the observation group after the treatment was obviously lower than that in the control group(P<0. 05). Conclusion: Polyene phosphatidylcholine injections combined with Hugan tablets in the treatment of liver injury is better than polyene phosphatidyl choline, which is worthy of clinical application.