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Objective: To explore the mechanism of Kuhuang injection in protecting the liver and alleviating jaundice by establishing the active components-target network and protein interaction network and analyzing the functions and pathways. Methods: The main active components of Kuhuang injection were obtained through traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and related literatures. The targets to treat hepatitis and jaundice of the active components of Kuhuang injection were predicted and screened by GeneCard and online Mendelian inheritance in man (OMIM). Cytoscape 3.6.1 software was used to construct the active component-target network, and STRING database and Cytoscape 3.6.1 software were used to construct the protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways involved in the targets were analyzed using the database for annotation, visualization and integrated discovery (DAVID). Results: The results showed that 16 active components of Kuhuang injection were screened and 85 targets were obtained. The results of network analysis showed that cellular processes, metabolic processes, and processes in response to stress were mainly involved in the effects of Kuhuang injection against hepatitis and jaundice. The results of target pathway analysis showed that the targets of Kuhuang injection for hepatitis and jaundice were mainly involved in mitogen-activated protein kinase (MAPK), Toll-like receptor, p53, neurotrophin and other signaling pathways. Conclusion: The anti-hepatitis and jaundice effects of Kuhuang injection are characterized by multiple components, multiple targets and multiple pathways, which might be through regulating MAPK, Toll-like receptor, p53, neurotrophin and other related pathways.
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Objective To investigate the compatibility and room light' s influence on Kuhuang injection diluted by 5%glucose,10% glucose, and fructose for injection within 48 hours at room temperature. Methods Kuhuang injections( high or low dosage) were diluted by 3 solutions at room temperature and were divided into light-exposed group and light-screening group. Stability were then studied by changes of appearance, pH value, particulates, contents of matrine and sophocarpine in the solutions. Results The Kuhuang injection solution remained clear within 48 hours, showing no obvious turbidity, sedimentation or change of appearance ( deep yellow clear solution ) . The pH of the low concentration group with 10% glucose injection exposed to room light in creased significantly at 6 h,which was less stable than the light-screening group.The particulate content was acceptable according to regulation. The Kuhuang injection compatibility solution with fructose injection changed into weak acidic pH, and the particulate content did not meet regulation criteria in the high concentration group. The contents of matrine did not change, while the contents of sophocarpine decreased in each group.Sophocarpine seemed more stable in the light-screening group than in the light-exposed group. Conclusion The fructose injection was not suitable as the solvent for Kuhuang injection.The solutions are more stable if protected from light, and should be used as early as possible to reduce the degradation of some effective components.
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Objective To investigate the compatibility and room light' s influence on Kuhuang injection diluted by 5%glucose,10% glucose, and fructose for injection within 48 hours at room temperature. Methods Kuhuang injections( high or low dosage) were diluted by 3 solutions at room temperature and were divided into light-exposed group and light-screening group. Stability were then studied by changes of appearance, pH value, particulates, contents of matrine and sophocarpine in the solutions. Results The Kuhuang injection solution remained clear within 48 hours, showing no obvious turbidity, sedimentation or change of appearance ( deep yellow clear solution ) . The pH of the low concentration group with 10% glucose injection exposed to room light in creased significantly at 6 h,which was less stable than the light-screening group.The particulate content was acceptable according to regulation. The Kuhuang injection compatibility solution with fructose injection changed into weak acidic pH, and the particulate content did not meet regulation criteria in the high concentration group. The contents of matrine did not change, while the contents of sophocarpine decreased in each group.Sophocarpine seemed more stable in the light-screening group than in the light-exposed group. Conclusion The fructose injection was not suitable as the solvent for Kuhuang injection.The solutions are more stable if protected from light, and should be used as early as possible to reduce the degradation of some effective components.
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OBJECTIVE:To establish a method for the content determination of matrine,sophocarpine,emodin,rhein,chloro-genic acid,sarkosaponin a,aloe-emodin in Kuhuang injection.METHODS:UPLC-MS/MS was adopted. The determination was per-formed on Phenomenex Kenetix C18 column with mobile phase consisted of methanol-0.1% formic acid(gradient elution)at the flow rate of 0.5 mL/min. The column temperature was set at 20 ℃,and injector temperature was set at 10 ℃. The equilibrium time was 4 min and sample size was 5 μL. Ionization mode was electrospray ionization with spray voltage of 5500 V and -4500 V,at-omizing air pressure of 4.14×105 Pa,heater pressure of 4.48×105 Pa,curtain air of 1.72×105 Pa and ion source temperature of 600 ℃. The work mode was multiple reaction monitoring mode. RESULTS:The linear range were 1.25-80.0 ng/mL for matrine (r=0.9993),1.10-70.0 ng/mL for sophocarpine(r=0.9995),0.16-10.5 ng/mL for emodin(r=0.9993),2.61-168 ng/mL for rhe-in (r=0.9993),1.50-96.0 ng/mL for chlorogenic acid (r=0.9993),1.48-94.5 ng/mL for sarkosaponin a (r=0.9996) and 6.11-391 ng/mL for aloe-emodin(r=0.9991). The limits of quantification were 0.061,0.109,0.041,1.313,0.500,0.492,3.055 ng/mL,limits of detection were 0.025,0.054,0.016,0.656,0.150,0.148,1.528 ng/mL. RSDs of precision,stability and reproducibility tests were all no more than 3%. The recoveries of them were 95.45%-99.45%(RSD=1.43%,n=6),97.50%-101.00%(RSD=1.50%,n=6),95.67%-101.73%(RSD=2.85%,n=6),97.17%-100.57%(RSD=1.16%,n=6),95.19%-98.90%(RSD=1.71%, n=6),95.38%-103.85%(RSD=3.39%,n=6),95.50%-101.17%(RSD=1.20%,n=6),respectively. CONCLUSIONS:The method is simple,effective,accurate,reliable and suitable for simultaneous determination for 7 components in Kuhuang injection.
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To systematically evaluate the effectiveness and safety of Kuhuang injection in treating viral hepatitis. Eight electronic databases and clinic trials were searched to collect randomized controlled trials for the effect of Kuhuang injection in the treatment of viral hepatitis. According to the Cochrane Handbook 5.1, two independent reviewers screened out the literatures, extracted data and assessed the quality of thestudies included. RevMan5.3 software was used for the data analysis. A total of 32 articles were included, involving 3 188 patients, including male 1 951 cases (61.2%), female 859 cases (26.9%), and 378 cases of unknown sex (11.9%). All the clinical studies showed a low quality. Due to the complication of diseases and difficulty in intervention measures, most trails were classified by the condition of diseases, and then a descriptive analysis was made. The results showed that the test group was better than the control group in total efficiency of treating severe icteric viral hepatitis, and the test group was advantageous over the control group in jaundice removal and liver function recovery rate in treating icteric hepatitis. In the Meta-analysis on the RCTs for icteric viral hepatitis, the total efficiency of Kuhuang injection + comprehensive treatment group was higher than that of the comprehensive treatment group （RR=1.35, 95%CI=[1.10,1.66], P=0.61）. In addition, when Kuhuang injection was dripped too fast, patients had such adverse reactionsas dizziness, palpitation, nausea, vomiting and skin rash, which could be relieved at a lower dripping speed.Based on the existing evidences, Kuhuang injection had a certain effect in treating viral hepatitis. Most clinic trails did not include viral hepatitis etiology, clinical classification and diversified intervention measures, which resulted in a high clinical heterogeneity and poor comparability between trails. Besides, most trials had a low methodological quality, which affected the authenticity of the results. Therefore, more high-quality, multi-center, large-sample, randomized double-blind controlled trialsarerequired to prove the evidences.
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Objective To explore the effect of Kuhuang injection on liver function and serum trace elements levels in patients with acute jaundice hepatitis.Methods 37 cases of acute jaundice hepatitis patients from December 2013 to April 2015 were selected and randomly assigned into treatment group and control group, 19 cases in control group were treated with potassium magnesium aspartate injection, 18 cases in treatment group with Kuhuang injection on the basis of control group.The liver function and serum trace elements were compared pre-and post-treatment.Results Compared with control group post-treatment, the level of serum cholyglycine (SCG) was significantly lower(P<0.05), the levels of total bilirubin (TBIL) and direct bilirubin (DBil) were lower(P<0.05), magnesium, copper, zinc levels were higher(P<0.05) and level of iron were lower(P<0.05)in treatment group.Conclusion Kuhuang injection has good clinical curative effect for the patients with acute jaundice hepatitis, we speculated that it might be possible to improve the liver function and levels of serum trace elements .
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Objective To evaluate the clinical efficiencies and safeties of S-adenosylmethionine (SAM ) in treatment of 34 patients with chronic hepatitis B complicated hyperbilirubinemia .Methods Patients which meet the diagnostic criteria were randomized into the group with treatment of SAM (the treatment group ,34 cases) and the group with Kuhuang injection (the contrast group ,35 cases) ,4 weeks for a course of treatment .The clinical efficacies and safeties were observed in the two groups .Results Compared with the contrast group ,the overall efficiency was better in the treatment group (91 .2% vs 68.6% , P<0 .05) ,and the curative effects of serum ALT ,serum bilirubin ,TBA levels were better in the treatment group after treatment (P<0 .01) .There were no adverse drug reactions in the treatment group and 3 cases with adverse drug reactions in the contrast group .Conclusion The clinical efficiencies and safeties of SAM treatment in patients with chronic hepatitis B com-plicated hyperbilirubinemia were better than that of Kuhuang injection .