Yinzhihuang oral liquid protects against non-alcoholic steatohepatitis via modulation of the gut-liver axis in mice.

Background: Yinzhihuang (YZH) oral liquid is a traditional Chinese medicine compound that has emerged as a promising therapeutic agent for non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the therapeutic effects of YZH on non-alcoholic steatohepatitis (NASH) and elucidate its underlying molecular mechanisms. Methods: Mice fed on a high-fat diet plus fructose/glucose drinking water (HFGD) were treated with YZH (30 mL/kg/d). The effects of YZH on mice with NASH were assessed through serological analysis and histological examination. Microbiota analysis based on 16S ribosomal ribonucleic acid (16S rRNA) and intestinal mucosal barrier function, serum inflammatory factors, hepatic macrophage infiltration, as well as hepatic toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NFκB) pathway were carried out to explore the mechanism of YZH for treatment of NASH. Results: Results of the current study found that YZH effectively reduced body weight gain and adiposity and alleviated hepatocyte steatosis, hepatocyte ballooning, liver tissue lobular inflammation, as well as fibrosis. It also reduced the accumulation of triglycerides, cholesterol, and free fatty acids in the liver of the treated mice and normalized serum aspartate transaminase, alanine transaminase, and glucose levels as well as lipid metabolism. Meanwhile, YZH treatment significantly decreased the abundance of harmful bacteria, such as Mucispirillum, Helicobacter, and Desulfovibrionaceae. Mechanistically, the present study found that YZH upregulated the expression of tight junction proteins, decreased serum lipopolysaccharide, interleukin 6, and tumor necrosis factor α levels, and increased interleukin 10 levels in serum. In the liver, YZH alleviated macrophage infiltration, especially that of pro-inflammatory macrophages. Moreover, it was found that YZH inhibited the canonical TLR4, MyD88, NFκB signaling pathway. Conclusions: In conclusion, YZH may be a new agent for the prevention of NASH. Further, YZH alleviates gut microbiota dysbiosis, restores the intestinal mucosal barrier, and inhibits the canonical TLR4, MyD88, NFκB signaling pathway.

Yinzhihuang Oral Liquid Ameliorates Hyperbilirubinemia Induced by δ-Aminolevulinic Acid and Novobiocin in Neonatal Rats.

Yinzhihuang oral liquid (YZH) is a traditional Chinese medicine that has been widely used in Asia to prevent and treat neonatal hyperbilirubinemia, but the published preclinical studies on its anti-hyperbilirubinemia effect are conducted in adult animals, partly due to the lack of preclinical neonatal hyperbilirubinemia animal models. In the present study, we tested six reagents to induce hyperbilirubinemia in neonatal rats, and established two appropriate neonatal hyperbilirubinemia rat models by subcutaneous injection of δ-Aminolevulinic acid (ALA, 200 mg/kg) or novobiocin (NOVO, 200 mg/kg). Oral treatment of YZH (80, 160 and 320 mg/kg) significantly decreased serum conjugated bilirubin levels in ALA-treated neonatal rats and serum unconjugated bilirubin levels in NOVO-treated neonatal rats, respectively. Additionally, pre-treatment of YZH also prevented the increase of serum bilirubin levels in both ALA- and NOVO-treated rats. Mechanistically, YZH significantly up-regulated the mRNA expression of genes involved in hepatic bilirubin disposition (organic anion-transporting polypeptide 1b2, Oatp1b2; multidrug resistance-associated protein 2, Mrp2) and bilirubin conjugation (UDP-glucuronosyltransferase 1a1, Ugt1a1). Additionally, YZH up-regulated the mRNA expression of cytochrome P450 1A1 (Cyp1a1), the target gene of aryl hydrocarbon receptor (AhR), and increased the nuclear protein levels of AhR in livers of neonatal rats. YZH and its two active ingredients, namely baicalin (BCL) and 4'-hydroxyacetophenone (4-HT), up-regulated the mRNA expression of AhR target genes (CYP1A1 and UGT1A1) and increased nuclear protein levels of AhR in HepG2 cells. In conclusion, the present study provides two neonatal hyperbilirubinemia animal models and evaluates the anti-hyperbilirubinemia effect and mechanisms of YZH in neonatal animals.

[Systematic review and Meta-analysis of effect of Yinzhihuang Oral Liquid in treatment of neonatal jaundice].

To systematically review effectiveness and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice. A systematic retrieval was performed throughout China National Knowledge Infrastructure( CNKI),Wan Fang,VIP,Sino Med and PubMed,Medline,Cochrane Library databases from the establishment to April 2019. Randomized controlled trials of Yinzhihuang Oral Liquid in treatment of neonatal hyperbilirubinemia were retrieved. Clinical studies in line with the inclusion criteria were involved for data extraction,and the quality of the included literatures was evaluated by the risk bias assessment tool in the Cochrane review manual. Finally,Meta-analysis was performed by Rev Man 5.3 software. A total of 30 studies were involved,involving 3 923 child patients,including1 940 in observation group and 1 983 in control group. According to the results of Meta-analysis,the total effective rate( RR = 1. 22,95%CI[1. 18,1. 26],P<0. 000 01),level of TBi L after treatment( MD =-38. 78,95%CI[-48. 38,-29. 18],P<0. 000 01),time to jaundice resolution( MD =-1. 76,95% CI[-2. 10,-1. 41],P < 0. 000 01) and daily average decrease value of bilirubin( MD =11. 67,95%CI[8. 89,14. 45],P<0. 000 01) of observation group were significantly better than those of control group,with statistically significant differences. Adverse reactions were reported in nine studies,mainly including diarrhea,vomiting,fever,rash and other symptoms,which did not affect the treatment effect. The effectiveness of Yinzhihuang Oral Liquid combined with conventional therapy in treating neonatal jaundice was better than conventional therapy alone,with little adverse reactions. However,most of literatures included had a low research quality,which impacted the reliability of the conclusion. Therefore,it is suggested to conduct more largesample-size,multicenter,scientifically designed,strictly implemented high-quality randomized controlled trials in the future,in order to study the efficacy and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice.

Systematic review and Meta-analysis of effect of Yinzhihuang Oral Liquid in treatment of neonatal jaundice / 中国中药杂志

To systematically review effectiveness and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice. A systematic retrieval was performed throughout China National Knowledge Infrastructure( CNKI),Wan Fang,VIP,Sino Med and PubMed,Medline,Cochrane Library databases from the establishment to April 2019. Randomized controlled trials of Yinzhihuang Oral Liquid in treatment of neonatal hyperbilirubinemia were retrieved. Clinical studies in line with the inclusion criteria were involved for data extraction,and the quality of the included literatures was evaluated by the risk bias assessment tool in the Cochrane review manual. Finally,Meta-analysis was performed by Rev Man 5.3 software. A total of 30 studies were involved,involving 3 923 child patients,including1 940 in observation group and 1 983 in control group. According to the results of Meta-analysis,the total effective rate( RR = 1. 22,95%CI[1. 18,1. 26],P<0. 000 01),level of TBi L after treatment( MD =-38. 78,95%CI[-48. 38,-29. 18],P<0. 000 01),time to jaundice resolution( MD =-1. 76,95% CI[-2. 10,-1. 41],P < 0. 000 01) and daily average decrease value of bilirubin( MD =11. 67,95%CI[8. 89,14. 45],P<0. 000 01) of observation group were significantly better than those of control group,with statistically significant differences. Adverse reactions were reported in nine studies,mainly including diarrhea,vomiting,fever,rash and other symptoms,which did not affect the treatment effect. The effectiveness of Yinzhihuang Oral Liquid combined with conventional therapy in treating neonatal jaundice was better than conventional therapy alone,with little adverse reactions. However,most of literatures included had a low research quality,which impacted the reliability of the conclusion. Therefore,it is suggested to conduct more largesample-size,multicenter,scientifically designed,strictly implemented high-quality randomized controlled trials in the future,in order to study the efficacy and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice.

Yinzhihuang oral liquid combined with phototherapy for neonatal jaundice: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Neonatal jaundice affects at least 481,000 newborns every year. Phototherapy is recommended but it's effects are limited and adverse reactions can occur. In China, phototherapy combined with Yinzhihuang oral liquid is also used for this condition. This systematic review evaluated the effectiveness and safety of combination therapy with Yinzhihuang oral liquid and phototherapy compared to phototherapy alone for treating neonatal jaundice. METHOD: A comprehensive literature search was performed in four Chinese databases, two English language databases and two trial registries from inception to June 2017. Two authors independently screened the citations and retrieved full publications for randomized trials on Yinzhihuang oral liquid combined with phototherapy for neonatal jaundice. The methodological quality of the trials was assessed according to the Cochrane Collaboration's tool for assessing risk of bias. Data were analyzed using RevMan 5.3. RESULT: Totally 17 trials (involving 2561 neonates) were included in this review. Fourteen of them had a high risk of bias. Significant differences were detected between combination therapy and phototherapy alone for serum bilirubin level (MD - 50.25 µmol/L, 95% CI -64.01 to - 36.50, I2 = 98%; 7 trials, post-hoc decision choosing random effects model), failure of jaundice resolution (RR 0.21, 95% CI 0.14 to 0.32, I2 = 0%; 11 trials, fixed effects model), and time to jaundice resolution (MD - 2.17 days, 95%CI -2.96 to - 1.38, I2 = 98%; 6 trials, random effects model). Adverse events were reported in eight trials but none were serious. Trial sequential analysis for serum bilirubin level suggested that the cumulative Z-curve (which represents 1478 participants) reached the required information size (DARIS = 1301 participants). CONCLUSION: Based on trials with low methodological quality, Yinzhihuang oral liquid combined with phototherapy seemed to be safe and superior to phototherapy alone for reducing serum bilirubin in neonatal jaundice. These potential benefits need to be confirmed in future trials using rigorous methodology. TRIAL REGISTRATION: Systematic review registration: [PROSPERO registration: CRD42016037691 ].

Yinzhihuang oral liquid in the treatment of neonatal jaundice: a meta-analysis.

CONTEXT: Yinzhihuang oral liquid, a well-known Chinese herbal formula, is a clinical drug for the treatment of neonatal jaundice, and a number of clinical trials have been published addressing this issue, but there is no comprehensive analysis that evaluates its efficacy for the treatment of newborn with hyperbilirubinaemia. OBJECTIVE: A meta-analysis was conducted to evaluate the efficacy of Yinzhihuang oral liquid on neonatal jaundice. METHODS: Search was performed throughout PubMed, Cochrane Library, EMBASE, Ovid, Wanfang, VIP Medicine Information System (VMIS) and China National Knowledge Infrastructure (CNKI) databases up to December 2015. The search terms were (Yinzhihuang oral liquid or Yinzhihuang oral solution), (neonatal jaundice or neonatal hyperbilirubinaemia), and (efficacy). Review Manager 5.2 software was used for analyzing the data. Data were pooled by using the random-effects models and expressed as relative ratio (RR), standardized mean difference (SMD) or mean difference (MD) with a 95% confidence interval (CI). The Cochrane tool was applied to assess the risk of bias of the trials. RESULTS: Yinzhihuang oral liquid in conjunction with other therapy increased effective rate of neonatal jaundice therapy (RR =1.14, 95%CI: 1.08-1.20). Yinzhihuang oral liquid significantly eliminated overproduced bilirubin which was measured by TSB or TCB at the third day and fifth day during the treatment {[third day, SMD = -1.63, 95%CI: -2.20 to (-1.06)], [fifth day, SMD = -5.00, 95%CI: -7.88 to (-2.12)]}; Yinzhihuang oral liquid significantly shortened jaundice subsiding time [MD = -3.20, 95%CI: -6.01to (-0.39)]. CONCLUSION: Yinzhihuang oral liquid can be considered as an effective treatment option for neonatal jaundice.

Determination of Five Index Components in Yinzhihuang Oral Liquid by Quantitative Analysis of Multi-components by Single Marker / 中国药师

Objective:To develop a method of quantitative analysis of multi-components by single marker ( QAMS) for five index components in Yinzhihuang oral liquid. Methods:Using baicalin as the reference,an HPLC method with a Venusil MP C18 (2) column (250 mm × 4. 6 mm,5 μm) was applied,the mobile phase was acetonitrile-0. 1% phosphoric acid with gradient elution,the flow rate was 1. 0 ml·min-1 ,the detection wavelength was 327 nm, the column temperature was 35℃ and the injection volume was 10μl. The relative correction factors among the five index components were detected by QAMS. The five index contents were determined respec-tively by an external standard method and QAMS, and the results obtained from the two different methods were compared to verify the practicability and stability of QAMS. Results: The established QAMS method was used to determine the five index components in 6 batches of Yinzhihuang oral liquid. There were no significant differences in the calculated values and the determined ones (P>0. 05). Conclusion:The QAMS method is simple,effective and accurate in determining the contents of five index components in Yinzhihuang oral liquid,which can be used for the quality control of Yinzhihuang oral liquid and provide reference for the further studies.

Yinzhihuang supplementary illumination analysis of humanized nursing in the treatment of neonatal jaundice / 中国生化药物杂志

Objective To investigate the effect of Yinzhihuang auxiliary light clinical effect of the treatment of neonatal jaundice, and analyze the treatment process right humanized nursing service measures. Methods 1100 children with jaundice from October 2015 to October 2016 were selected and randomly divided into the study group (n=550) and the control group (n=550). The control group with jaundice in conventional treatment combined with blue light irradiation, the study group jaundice in the control group treated with Yinzhihuang oral liquid. The clinical efficacy of two groups of jaundice children was recorded, and the data were analyzed by statistical test (SPSS). Results The total effective rate of clinical treatment in children with jaundice in the study group (94.91%) was significantly better than that in the control group the total effective rate of clinical treatment was 70.36% (P<0.05). Conclusion In the blue light plus can rise to the ideal effect of adjuvant therapy of neonatal jaundice with Yinzhihuang oral liquid, can improve the patients clinical curative effect, combined with humanized nursing service or the prognosis and quality of life of children with strong support.

Determination of Five Index Components in Yinzhihuang Oral Liquid by Quantitative Analysis of Multi-components by Single Marker / 中国药师

Objective:To develop a method of quantitative analysis of multi-components by single marker ( QAMS) for five index components in Yinzhihuang oral liquid. Methods:Using baicalin as the reference,an HPLC method with a Venusil MP C18 (2) column (250 mm × 4. 6 mm,5 μm) was applied,the mobile phase was acetonitrile-0. 1% phosphoric acid with gradient elution,the flow rate was 1. 0 ml·min-1 ,the detection wavelength was 327 nm, the column temperature was 35℃ and the injection volume was 10μl. The relative correction factors among the five index components were detected by QAMS. The five index contents were determined respec-tively by an external standard method and QAMS, and the results obtained from the two different methods were compared to verify the practicability and stability of QAMS. Results: The established QAMS method was used to determine the five index components in 6 batches of Yinzhihuang oral liquid. There were no significant differences in the calculated values and the determined ones (P>0. 05). Conclusion:The QAMS method is simple,effective and accurate in determining the contents of five index components in Yinzhihuang oral liquid,which can be used for the quality control of Yinzhihuang oral liquid and provide reference for the further studies.

Yinzhihuang supplementary illumination analysis of humanized nursing in the treatment of neonatal jaundice / 中国生化药物杂志

Objective To investigate the effect of Yinzhihuang auxiliary light clinical effect of the treatment of neonatal jaundice, and analyze the treatment process right humanized nursing service measures. Methods 1100 children with jaundice from October 2015 to October 2016 were selected and randomly divided into the study group (n=550) and the control group (n=550). The control group with jaundice in conventional treatment combined with blue light irradiation, the study group jaundice in the control group treated with Yinzhihuang oral liquid. The clinical efficacy of two groups of jaundice children was recorded, and the data were analyzed by statistical test (SPSS). Results The total effective rate of clinical treatment in children with jaundice in the study group (94.91%) was significantly better than that in the control group the total effective rate of clinical treatment was 70.36% (P<0.05). Conclusion In the blue light plus can rise to the ideal effect of adjuvant therapy of neonatal jaundice with Yinzhihuang oral liquid, can improve the patients clinical curative effect, combined with humanized nursing service or the prognosis and quality of life of children with strong support.

[Meta-analysis of Yinzhihuang oral liquid in treatment of intrahepatic cholestasis of pregnancy].

To systematically review the clinical efficacy and safety of Yinzhihuang oral liquid in the treatment of intrahepatic cholestasis of pregnancy(ICP). Literatures published by June 2016 were searched in databases, such as Medline, Pubmed, Cochrane Library, China National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Full-text Database(VIP), Chinese biomedical literature database(CBM), and Wanfang Database. Randomized controlled trials(RCT) of Yinzhihuang oral liquid were collected according to the inclusion criteria, and the methodological quality of selected literatures was evaluated. The Meta-analysis was conducted by using RevMan 5.3 software. A total of 7 RCTs involving 711 patients were included. The results of Meta-analysis showed that, compared with control group, Yinzhihuang oral liquid significantly alleviated pruritus symptoms[MD=－0.68, 95%CI(－0.95,－041), P<0.000 01], reduced blood biochemical indexes including TBA[MD=－7.23, 95%CI (－10.88,－3.58), P=0.000 1], TB[MD=－1.90, 95%CI(－3.09,－0.70), P=0.002], ALT[MD=－39.08, 95%CI (－56.46,－21.70), P<0.000 1], and CG [MD=－0.71, 95%CI(－0.89,－0.52), P<0.000 01]. In the respect of pregnancy outcome, Yinzhihuang oral liquid can distinctly improve birth weight [MD=430.03, 95%CI (219.28, 640.78), P<0.000 1]. However, there was no significant difference in cesarean section rate [OR=0.93, 95%CI (0.36, 2.36), P=0.87], preterm birth rates [OR=0.63, 95%CI (0.28, 1.42), P=0.26], and neonatal asphyxia rate [OR=0.50, 95%CI (0.18, 1.43), P=0.20]. Yinzhihuang oral liquid showed better efficiency and slighter adverse reaction. However, more rigorously designed, double-blind, randomized controlled trials with large sample size and high quality are required to provide further evidences.

Meta-analysis of Yinzhihuang oral liquid in treatment of intrahepatic cholestasis of pregnancy / 中国中药杂志

To systematically review the clinical efficacy and safety of Yinzhihuang oral liquid in the treatment of intrahepatic cholestasis of pregnancy(ICP). Literatures published by June 2016 were searched in databases, such as Medline, Pubmed, Cochrane Library, China National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Full-text Database(VIP), Chinese biomedical literature database(CBM), and Wanfang Database. Randomized controlled trials(RCT) of Yinzhihuang oral liquid were collected according to the inclusion criteria, and the methodological quality of selected literatures was evaluated. The Meta-analysis was conducted by using RevMan 5.3 software. A total of 7 RCTs involving 711 patients were included. The results of Meta-analysis showed that, compared with control group, Yinzhihuang oral liquid significantly alleviated pruritus symptoms[MD=－0.68, 95%CI(－0.95,－041), P<0.000 01], reduced blood biochemical indexes including TBA[MD=－7.23, 95%CI (－10.88,－3.58), P=0.000 1], TB[MD=－1.90, 95%CI(－3.09,－0.70), P=0.002], ALT[MD=－39.08, 95%CI (－56.46,－21.70), P<0.000 1], and CG [MD=－0.71, 95%CI(－0.89,－0.52), P<0.000 01]. In the respect of pregnancy outcome, Yinzhihuang oral liquid can distinctly improve birth weight [MD=430.03, 95%CI (219.28, 640.78), P<0.000 1]. However, there was no significant difference in cesarean section rate [OR=0.93, 95%CI (0.36, 2.36), P=0.87], preterm birth rates [OR=0.63, 95%CI (0.28, 1.42), P=0.26], and neonatal asphyxia rate [OR=0.50, 95%CI (0.18, 1.43), P=0.20]. Yinzhihuang oral liquid showed better efficiency and slighter adverse reaction. However, more rigorously designed, double-blind, randomized controlled trials with large sample size and high quality are required to provide further evidences.

Effectiveness and Safety of Yinzhihuang Oral Liquid in the Adjuvant Treatment of Neonatal Jaundice:A Sys-tematic Review / 中国药房

OBJECTIVE:To systematically review the effectiveness and safety of Yinzhihuang oral liquid in the adjuvant treat-ment of neonatal jaundice,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from CJFD,VIP Da-tabase,Wanfang Database,Medline and EMBase,randomized controlled trials(RCT)about the effectiveness of Yinzhihuang oral liquid(test group)based on the canventional treatment(control group)in the adjuvant treatment of neonatal jaundice were collect-ed,and Meta-analysis was performed by using Rev Man 5.2 software after data extracting and quality evaluating by modified Jadad. RESULTS:Totally 12 RCTs were enrolled,involving 1585 patients. Results of Meta-analysis showed total effective rate [OR=0.19,95%CI(0.12,0.30),P<0.001],serum total bilirubin levels [MD=-40.78,95%CI(-42.68,-38.89),P<0.001] and time of bilirubin decreased to normal [MD=-2.56,95%CI(-2.72,-2.40),P<0.001] in test group were significantly better than control group,the differences were statistically significant between 2 groups;3 reports of adverse reactions showed scme children had vomiting and mild diarrhea,they were improved after symptomatic treatment,and it did not affect the treatment. CONCLU-SIONS:The effectiveness of Yinzhihuang oral liquid is good in the adjuvant treatment of neonatal jaundice,with mild adverse reac-tions.

Clinical Observation of Yinzhihuang Oral Liquid in the Adjuvant Treatment of Neonatal Breast-feeding Faun-dice / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of Yinzhihuang oral liquid in the adjuvant treatment of neo-natal breast-feeding faundice. METHODS:112 newborns with faundice were randomly divided into control group and observation group. Control group stopped breast-feeding for 3 d and given artificial feeding,as well as keeping warm,nutritional support, maintaining water and electrolyte and acid-base balance,blue light irradiation and severe patients were given liver protection,en-zyme inducers;observation group was additionally given Yinzhihuang oral liquid 10 ml,twice a day. The treatment course was 7 d. Clinical efficacy,and serum total bilirubin(TBIL)level before and after treatment,and incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,the difference was statistically significant(P0.05). CONCLUSIONS:Based on the conventional treatment,Yinzhihuang oral liquid can be used in the adjuvant treatment of neonatal breast-feeding faundice,with good efficacy and good safety.