Yinchenhao Decoction Research Articles

Identification of the active compounds and significant pathways of yinchenhao decoction based on network pharmacology.

Yinchenhao decoction (YCHD) is a traditional Chinese medicine formulation, which has been widely used for the treatment of jaundice for 2,000 years. Currently, YCHD is used to treat various liver disorders and metabolic diseases, however its chemical/pharmacologic profiles remain to be elucidated. The present study identified the active compounds and significant pathways of YCHD based on network pharmacology. All of the chemical ingredients of YCHD were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Absorption, distribution, metabolism and excretion screening with oral bioavailability (OB) screening, drug-likeness (DL) and intestinal epithelial permeability (Caco-2) evaluation were applied to discover the bioactive compounds in YCHD. Following this, target prediction, pathway identification and network construction were employed to clarify the mechanism of action of YCHD. Following OB screening, and evaluation of DL and Caco-2, 34 compounds in YCHD were identified as potential active ingredients, of which 30 compounds were associated with 217 protein targets. A total of 31 significant pathways were obtained by performing enrichment analyses of 217 proteins using the JEPETTO 3.x plugin, and 16 classes of gene-associated diseases were revealed by performing enrichment analyses using Database for Annotation, Visualization and Integrated Discovery v6.7. The present study identified potential active compounds and significant pathways in YCHD. In addition, the mechanism of action of YCHD in the treatment of various diseases through multiple pathways was clarified.

Study on major antitumor components in Yinchenhao decoction in vitro and in vivo based on hollow fiber cell fishing coupled with high performance liquid chromatography.

Hollow fiber cell fishing (HFCF) based on human hepatoma cell HepG-2 or human renal tubular cell ACHN coupled with high performance liquid chromatography/ultraviolet detection (HPLC/UV) was developed and used for simultaneous study of the major antitumor active components in a formula of Yinchenhao decoction (YCHD) in vitro and in vivo, and in its constituent herbs, namely, Artemisia capillaris Thunb, Gardenia jasminoides Ellis, Radix et Rhizoma Rhei in vitro. Before application, chlorogenic acid, geniposide, p-hydroxyacetophenone, crocin and rhein were chosen as model compounds, the various validations, e.g., cell growth and cell viability on the fiber inner wall, binding between fiber active center and component, repeatability of retention time or relative peak area of the active components were investigated. We screened and identified the major antitumor active components of YCHD, verified their synergetic or antagonistic effect, correlated the major active components between in vitro and in vivo and determined major effective components. Our study will serve as a valuable reference in probing the antitumor material basis of YCHD and its three constituent herbs, as well as in identifying novel clinical aspects of traditional Chinese medicines. The results showed that HCFC-HPLC is a simple, rapid, and reliable method that simultaneously researches the interaction between multiple targets and multiple components of herbal medicine.

Qingre Lishi Tuihuang therapy for acute icteric hepatitis B: A systematic review

ObjectiveTo assess the efficacy of Qingre Lishi Tuihuang therapy (QLTT) for acute icteric hepatitis B infection. MethodsEight electronic databases were searched from inception to December 2016 with no language restrictions for reports of randomized controlled trials evaluating the effect of QLTT treating acute icteric hepatitis B. Two researchers independently extracted detailed data and assessed methodological quality. Review Manager 5.3.0 software was used to analyze the data. ResultsA total of 13 randomized controlled trials involving 2238 participants were included in this review. The methodological quality was generally poor. The results indicated that supplemented Yinchenhao decoction combined with non-specific treatments was more effective in improving the cure rate (risk ratio = 1.80; 95% CI 1.21–2.68) and reducing the serum levels of total bilirubin (mean difference = −29.74; 95% CI −31.91 to −27.57) and aspartate aminotransferase. Other self-made prescriptions conforming to QLTT plus non-specific treatments had beneficial effect for acute icteric hepatitis B in curing this disease (risk ratio = 1.48; 95% CI 1.27–1.73), as well as for negative seroconversion of HBeAg (risk ratio = 1.39; 95% CI 1.11–1.74). Supplemented Yinchenhao decoction plus non-specific treatments was more effective than other self-made prescriptions conforming to QLTT in reducing serum total bilirubin level. ConclusionQingre Lishi Tuihuang therapy appears to improve effect based on non-specific treatments for the treatment of acute icteric hepatitis B. However, it is premature to draw confirmative conclusions, owing to the poor methodological quality and high clinical heterogeneity of the included trials. Further well-designed clinical randomized controlled trials with large sample sizes should be undertaken.

Simultaneous quantitation of 14 active components in Yinchenhao decoction with an ultrahigh performance liquid chromatography-diode array detector: Method development and ingredient analysis of different commonly prepared samples.

J. Sep. Sci. 2016, 39, 4147-4157 DOI: 10.1002/jssc.201600284 Yinchenhao decoction (YCHD) is a famous Chinese herbal formula recorded in the Shang Han Lun which was prescribed by Zhongjing Zhang during 150-219 AD. A novel quantitative analysis method was developed, based on ultrahigh performance liquid chromatography coupled with a diode array detector for the simultaneous determination of 14 main active components in Yinchenhao decoction. Furthermore, the method has been applied for compositional difference analysis of the 14 components in eight normal extraction samples of Yinchenhao decoction, with the aid of hierarchical clustering analysis and similarity analysis. The present research could help hospital, factory and lab choose the best way to make Yinchenhao decoction with better efficacy.

Simultaneous quantitation of 14 active components in Yinchenhao decoction by using ultra high performance liquid chromatography with diode array detection: Method development and ingredient analysis of different commonly prepared samples.

We developed a novel quantitative analysis method based on ultra high performance liquid chromatography coupled with diode array detection for the simultaneous determination of the 14 main active components in Yinchenhao decoction. All components were separated on an Agilent SB-C18 column by using a gradient solvent system of acetonitrile/0.1% phosphoric acid solution at a flow rate of 0.4 mL/min for 35 min. Subsequently, linearity, precision, repeatability, and accuracy tests were implemented to validate the method. Furthermore, the method has been applied for compositional difference analysis of 14 components in eight normal-extraction Yinchenhao decoction samples, accompaniedby hierarchical clustering analysis and similarity analysis. The result that all samples were divided into three groups based on different contents of components demonstrated that extraction methods of decocting, refluxing, ultrasonication and extraction solvents of water or ethanol affected component differentiation, and should be related to its clinical applications. The results also indicated that the sample prepared by patients in the family by using water extraction employing a casserole was almost same to that prepared using a stainless-steel kettle, which is mostly used in pharmaceutical factories. This research would help patients to select the best and most convenient method for preparing Yinchenhao decoction.

茵陈蒿汤治疗湿热证的应用及其作用机制的研究进展

茵陈蒿汤作为治疗湿热证的经典方，在临床上不仅用于治疗湿热黄疸或肝胆疾病，也常用于辨治湿热为患的皮肤病、内分泌疾病以及妇产科疾病等，其药理学疗效机制在于调节湿热证的主要病理变化。本文基于配伍规律，临床应用，疗效机制及其所作用于湿热证的病理机制，综述了茵陈蒿汤近年来的研究进展，为今后进一步深入开展茵陈蒿汤的研究工作提供参考。 As a classic traditional Chinese formula for treatment of damp-heat syndrome, Yinchenhao decoc-tion can no merely be used to treat Damp heat jaundice or liver and gall diseases, but also be ap-plied to the damp-heat syndrome-based treatment for dermatoses, endocrinopathy, gynecological and obstetric diseases etc. The pharmacological mechanism due to regulate and control the main pathological events of damp-heat syndrome in diseases. In this article, according to compatibility law, clinical application, therapeutic effect and mechanism and pathological mechanism of damp- heat syndrome, we reviewed the recent advances in the researches on Yinchenhao decoction to provide a reference for further studies.

Effects of Yinchenhao decoction on self-regulation of renin-angiotensin system by targeting angiotensin converting enzyme 2 in bile duct-ligated rat liver.

In order to investigate whether Yinchenhao decoction (YCHD) attenuates hepatic fibrogenesis in the bile duct ligation (BDL) model via recovering and restoring the self-regulation and balance of the renin-angiotensin system (RAS), 33 specific-pathogen-free (SPF) male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows: G1, the sham group (n=4); G2, BDL 7-day group (n=5); G3, BDL+YCHD 430 mg/mL (n=8); G4, BDL+losartan 0.65 mg/mL (ARB group, n=8); G5, model group (BDL without any treatment, n=8). YCHD and losartan (10 mL·kg(-1)·day(-1)) were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respectively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IDBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological changes were observed by transmission electron microscopy (TEM) and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system (RAS) components including angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), ACE2, angiotensin II (AngII) as well as transforming growth factor β1 (TGFβ1). The experimental data were analyzed by principle component analytical method of pattern recognition. The results showed that biochemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group (P<0.05). Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups (P<0.05). Serum AST level in G3 was significantly lowered than in G5 group (P<0.05), but there was no significant difference in ALT among G3, G4 and G5 groups (P>0.05). Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression levels of ACE2, ACE, AngII, AT1R and TGFβ1 in G2, G3 and G4 groups were significantly higher than in sham group (P<0.05), and lower than in G5 group (P<0.05). However, the differences among G2, G3 and G4 groups were not significant (P>0.05). ACE2 protein expression in G3 group was significantly higher than in G2 group (P<0.05) and there was no significant difference in comparison with G4 group (P>0.05). Moreover, the protein expression of TGFβ1 in G3 group was significantly lower than in G5 and G4 groups (P<0.05). Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFβ1 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.

Immunomodulation and liver protection of Yinchenhao decoction against concanavalin A-induced chronic liver injury in mice

ObjectiveThis study investigated the immunoregulatory and protective roles of Yinchenhao decoction, a compound of Chinese herbal medicine, in a mouse model of concanavalin A (ConA)-induced chronic liver injury. MethodsFemale BalB/c mice were randomly divided into 4 groups: normal control, ConA model, ConA model treated with Yinchenhao decoction (400 mg/kg, orally), and ConA model treated with dexamethasone (0.5 mg/kg, orally). All treatments were given once a day for 28 d. Except of the normal control, mice received tail vein injection of ConA (10 mg/kg) on days 7, 14, 21, and 28, at 1 h after treatment with Yinchenhao decoction or dexamethasone or saline to induce chronic liver injury. ResultsRepeated ConA injection induced chronic liver injury, which was evidenced by inflammatory cell infiltration and necrosis, increased serum alanine aminotranferease activities, decreased albumin levels, and an imbalanced expression of immunoregulatory genes in the liver tissues including significantly enhanced interferon-γ, interleukin-4, monocyte chemotactic protein-1, and cluster of differentiation 163 mRNA levels, and reduced tumor necrosis factor-α and interleukin-6 mRNA levels. Treatment with Yinchenhao decoction significantly reversed the ConA-induced changes in immunoregulatory gene expression in the liver tissues, reduced serum alanine aminotranferease activity, enhanced serum albumin level, and attenuated the extent of liver inflammation and necrosis. Furthermore, Yinchenhao decoction did not result in hepatocyte degeneration and spleen weight loss that were observed in mice received long-term treatment with dexamethasone. ConclusionYinchenhao decoction treatment protected liver against the ConA-induced chronic liver damage and improved liver function, which were associated with the modulation of gene expression related to immune/inflammatory response.

Apoptosis of human pancreatic carcinoma cell-1 cells induced by Yin Chen Hao Decoction.

To evaluate human pancreatic carcinoma cell line (PANC-1) cells apoptosis and Bcl-2 and Bax expression induced by Yin Chen Hao Decoction (YCHD). The cell growth inhibitory rate was determined by MTT assay. Apoptosis of PANC-1 cells before and after treatment with YCHD was determined by TUNEL staining. Expression of the apoptosis-associated genes, Bcl-2 and Bax, was detected by immunohistochemical staining and reverse transcription -PCR. YCHD inhibited the growth of PANC-1 cells. Following treatment with YCHD for 24-96 h, the apoptotic rate of PANC-1 cells increased with time. In addition, the positive rate of Bcl-2 protein expression decreased in a time-dependent manner, whereas the positive rate of Bax protein expression increased in a time-dependent manner. Following treatment of with YCHD for 24-96h, expression of BAX mRNA increased gradually and BCL-2 mRNA reduced gradually with time. YCHD induces apoptosis of PANC-1 cells mediated in part via up-regulation of BAX and down-regulation of BCL-2.

A practical method for the rapid detection and structural characterization of major constituents from traditional Chinese medical formulas: analysis of multiple constituents in Yinchenhao Decoction

A rapid characterization process of major constituents from Yinchenhao Decoction using FBF algorithms.

Reverse effect of Yinchenhao decoction in dimethyl nitrosamine-induced hepatic fibrosis in rats

To discuss the reverse effect of Yinchenhao decoction(YCHD) in dimethyl nitrosamine (DMN)-induced hepatic fibrosis in rats. The rat hepatic fibrosis model was established through the intraperitoneal injection with 1% dimethyl nitrosamine (DMN) with a dose of 1.0 mL x kg(-1) x d(-1) for consecutively three weeks, once for the first three days of each. The rats were randomly divided into six groups: the silymarin positive control group (50.0 mg x kg(-1) x d(-1), YCHD high (20.0 g x kg(-1) d(-1)), middle (8.0 g x kg(-1) x d(-1)) and low (3.2 g x kg(-1) x d(-1)) dose groups, the model group and the normal control group. The model group and the normal control group were orally administered with normal saline for consecutively five weeks. The pathologic changes in liver tissues were observed by HE staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), g-glutamyltransferase (g-GGT), hyaluronic acid (HA), laminin (LN), collagen type IV (CIV) and type III procollagen amino terminal peptide (PIIINP) in serum were determined. The metabolite profiling of amino acid and the content of hydroxyproline in liver tissues were also measured. Compared with the model group, YCHD high and middle dose groups could significantly reverse the pathologic changes in liver tissues of rats. YCHD could reduce the levels of ALT, AST, gamma-GGT, HA, LN, CIV, PIIINP in serum and the content of hydroxyproline in liver tissues in a dose-dependent manner, and altered the metabolite profiling of amino acid in rat liver tissues. YCHD has the effect in reversing dimethyl nitrosamine induced hepatic fibrosis in rats.

Yinchenhao decoction adjustment for treatment of nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

Yinchenhao decoction adjustment for treatment of nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

Rational Daily Administration Times of Yinchenhao Decoction in Rats with Jaundice Based on PD/PK

ObjectiveTo study the rational daily administration times of Yinchenhao Decoction (YCHD) when it was used to treat experimental jaundice in rats based on pharmacodynamics/pharmacokinetics model. MethodsRats were modeled by 4% 1-naphthylisothiocyanate (75 mg/kg) for 48 h, then YCHD was drenched with doses of 0.324 g/kg (extract, calculated with the clinical dosage) once, 0.162 g/kg twice, and 0.108 g/kg thrice a day, respectively. The total bile and the flow rate of bile were observed after the first administration; Blood samples collected from the orbital sinus at different intervals were used to investigate the levels of liver enzymes (ALT and AST) and bilirubins (TBIL and DBIL), and determine the concentration of 6,7-dimethoxycoumarin (DME) in the plasma using UPLC at the same time, then we obtained the time-effect and time-dose curves. The rational daily administration times of YCHD when treating experimental jaundice were determined based on the comprehensive analysis of time-effect and time-concentration relationships. ResultsWithin 10 h the total bile of rats which were administered once daily (G1) was 1.65 and 1.33 times higher than that of twice and thrice (G2 and G3) a day, respectively, and the four biochemical indexes (TBIL, ALT, DBIL, and AST) of G1 decreased faster than those of G2 and G3 (P < 0.05). On the other hand, the blood drug level of DME when administrated once daily could maintain at a higher level for a longer time, and its Cmax and AUC0→t were higher than those of G2 and G3, which might be the main reason why its effect was the most significant. ConclusionIt is more appropriate to administrate once daily when YCHD is used to treat jaundice.

Formula-syndrome correlation study of three classical anti-jaundice formulas in inhibition of liver fibrosis induced by dimethylnitrosamine in rats

To investigate the effects of three classical anti-jaundice formulas Yinchenhao Decoction (YCHD). Yinchen Wuling San (YCWLS) and Zhizi Baipi Decoction (ZZBPD) on liver fibrosis induced by dimethylnitrosamine (DMN) in rats and explore the formula-syndrome relationship. Forty-eight rats were weighted, and divided into five groups: normal control, DMN, YCHD, YCWLS and ZZBPD groups using stratified random method. Liver fibrosis in rats was induced by intraperitoneal injection of DMN for 4 weeks at the dosage 10 mg/kg body weight, once per day for 3 consecutive days in each week. Each groups was gavaged with distilled water (control or model group), YCHD, YCWLS and ZZBPD respectively in the last 2-week modeling period. At the end of the 4th week, rats were sacrificed and their blood sample and liver tissue were taken for detecting pathology and analyzing of hydroxyproline (Hyp) and liver function. Compared with the normal control group, DMN model group showed liver damage and liver fibrosis with remarkably increased Hyp content (P<0.01) and abnormal liver function (P<0.01). Liver fibrosis induced by DMN in rats was improved by administration of YCHD. Compared with DMN model group, content of Hyp was decreased remarkably (P<0.01) and liver function and hepatic histology were improved significantly after 2 weeks of YCHD treatment (P<0.05 or P<0.01)., and content of hepatic Hyp was decreased in the ZZBPD groups. Comparison of various parameters between groups showed that content of serum total bilirubin was decreased significantly in the YCWLS group (P<0.01), and content of hepatic Hyp was decreased in the ZZBPD group. Efficacy of YCHD in inhibition of liver fibrosis induced by DMN in rats is far better than YCWLS and ZZBPD. The pathogenesis of the liver fibrosis induced by DMN is mainly damp-heat. In addition, both damp and heat pathogenic factors play very important role in this model. The syndrome is highly correlated with the prescription YCHD.

Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction (茵陈蒿汤) treatment

To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate (ANIT)-induced experimental hepatic injury after oral administration of Yinchenhao Decoction (, YCHD) using an ultra pressure liquid chromatography (UPLC) method. Rats were divided into a normal group and a model group, after modeled by 4% ANIT (75 mg/kg) for 48 h, they were orally administrated with YCHD extract at the dose of 0.324 g/kg, and then blood was collected from their orbital sinus after different intervals. Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] and bilirubins [total bilirubin (TBIL), direct bilirubin (DBIL)], the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC, and the pharmaceutical parameters were calculated with DAS2.1.1 software. The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained. Their time to maximum plasma concentration (t(max)) were both 0.25 h, the maximum concentration (C(max)) were 4.533 μg/mL and 6.885 μg/mL, and their area under concentration-time curve (AUC)(0→24h) were 16.272 and 32.981, respectively. There was a 51.88% and 100.46% increase in C(max) and AUC(0-t) (P<0.05), but there showed a 45.52% and 92.93% reduction in clearance of drug and volum of distribution (P<0.05), respectively. Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD, the absorption and distribution process was accelerated in liver injured rats, but the metabolism and elimination process was slowed. And this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.

Chinese herbal medicine in the treatment of nonalcoholic fatty liver disease

Chinese herbal medicine has developed new therapies for nonalcoholic fatty liver disease (NAFLD) based on its unique theory system and substantial herb remedies. In this review, 21 traditional Chinese herbs were introduced for their potential benefit in the treatment of NAFLD. Majority of them are evaluated by experimental studies and few by multicenter clinical trials. Herbal monomers as berberine and resveratrol, extracts from Polygonum hypoleucum Ohwi, and Artemisia sacrorum Ledeb., and formulae including Yinchenhao Decoction (, YCHD), Qushi Huayu Decoction (, QSHYD), and Danning Tablet () were discussed in detail on their therapeutic potentials. Most of these herbal medicines were proved to improve biochemical and histological changes of NAFLD both in vitro and in vivo. Also, their therapeutic activities were associated with inhibiting lipid accumulation through adenosine monophosphate-activated protein kinase activation or upregulating low-density lipoprotein receptor (LDLR) expression, alleviating lipid peroxidation, and reducing the production of inflammatory cytokines. Although the efficacy and safety of these herbal medicines needed to be evaluated in multicenter large-scale clinical trials, Chinese medicine is promising and effective for preventing and treating NAFLD disease.

Effects of Yinchenhao Decoction ( ) for Non-alcoholic Steatohepatitis in Rats and Study of the Mechanism

To observe the effects of Yinchenhao Decoction (see text) for non-alcoholic steatohepatitis (NASH) in rats and study the mechanism. Total 18 male SD rats were randomly divided into a normal control group, a model group and a treatment group, 6 rats in each group. Rats in the model and treatment groups were fed with high-fat forage for 10 weeks to prepare the NASH model, and the rats in the treatment group were administrated with Yinchenhao Decoction from the 6th week for 5 weeks. All rats were sacrificed at the end of the 10th week and the samples were collected. Serum alanine aminotransferase (ALT) activity, tumor necrosis factor-alpha (TNF-alpha) level, and hepatic triglyceride (TG) and free fatty acid (FFA) contents were determined. Hepatic pathological changes were detected by HE staining. Serum ALT activity, TNF-alpha level, hepatic TG and FFA contents, and the fatty deposition in hepatocytes were significantly reduced in the rats of the treatment group. Yinchenhao Decoction has good therapeutic effects for NASH, protecting the liver function and reducing the fatty deposition in liver, which are possibly related with reduction of FFA content and inhibition of TNF-alpha expression.

Effects of Chinese herbal medicine Yinchenhao Decoction on expressions of apoptosis-related genes in dimethylnitrosamine- or carbon tetrachloride-induced liver cirrhosis in rats

To investigate the different efficacy of Yinchenhao Decoction (YCHD), a compound traditional Chinese herbal medicine, for liver cirrhosis induced by dimethylnitrosamine (DMN) or carbon tetrachloride (CCl(4)) in rats. To induce liver fibrosis, 0.5% DMN solution (2mL/kg body weight, i.p.) was given three consecutive days a week to male Wistar rats for 4 weeks. Cirrhotic rats were randomly divided into DMN group, YCHD group, Xiaochaihu decoction group by the end of the fourth week to accomplish a 2-week recipe treatment course. In CCl(4)-induced liver fibrosis model, 50% CCl(4)-olive solution was injected subcutaneously to rats at a dose of 2 mL/kg body weight twice a week to duplicate rat cirrhosis model. After 8 weeks, rats were divided into CCl(4) group, CCl(4) plus YCHD group and Xiaochaihu decoction group. For the YCHD group, YCHD was administered intragastrically once a day for 4 weeks. For DMN or CCl(4) model, by the end of 6 or 12 weeks respectively, rats were sacrificed for sampling to detect liver function, hepatic histological changes, hydroxyproline (Hyp) content and apoptosis-related gene expressions. In DMN liver fibrosis model, hepatic fibrosis was obvious at week 2 and cirrhosis was evident at week 4 in DMN-treated rats. Compared to 6-week DMN group, hepatic pathological changes and liver function were improved significantly and content of Hyp decreased remarkably in YCHD group. In CCl(4)-induced liver fibrosis model, hepatic fibrosis was obvious at 8 weeks and cirrhosis was evident at 12 weeks in CCl(4)-treated rats. Compared to 12-week CCl(4) group, hepatic pathological changes and liver function were not obviously improvement in YCHD group. The results of gene chip showed that YCHD significantly decreased Fas, Bax and caspase-3 gene expressions, and increased Bcl-xL gene expression in the liver of DMN model. However, in the model induced by CCl(4), YCHD did not inhibit hepatocyte apoptosis induced by CCl(4), but increased tyrosine kinase receptor gene expression by 4.8 times. YCHD exerts more significant therapeutic effects on DMN-induced than CCl(4)-induced cirrhosis in rats in Hyp content and pathological change in liver tissue.

Comparative study on the protective effects of Yinchenhao Decoction (茵陈蒿汤) against liver injury induced by α-naphthylisothiocyanate and carbon tetrachloride

To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine. The liver injury in the model rat was induced by alpha-naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl(4) ) respectively, and the effects of Yinchenhao Decoction (, YCHD), a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic, on the two liver injury models were evaluated by analyzing the serum level of alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP), malondialchehyche (MDA), total bilirubin (T-BIL), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) as well as the ratio of liver weight to body weight. The experimental data were analyzed by principal component analytical method of pattern recognition. The ratio of liver weight to body weight was significantly elevated in the ANIT and CCl(4) groups when compared with that in the normal control (P<0.01). The contents of ALT and T-BIL were significantly higher in the ANIT group than in the normal control (P<0.05,P<0.01), and the levels of AST, ALT and ALP were significantly elevated in CCl(4) group relative to those in the normal control P<0.01). In the YCHD group, the increase in AST, ALT and ALP levels was significantly reduced (P<0.05, P<0.01), but with no significant increase in serum T-BIL. In the CCl(4) intoxicated group, the MDA content was significantly increased and SOD, GSH-PX activities decreased significantly compared with those in the normal control group, respectively (P<0.01). The increase in MDA induced by CCl(4) was significantly reduced by YCHD P<0.05). YCHD showed significant effects on preventing liver injury progression induced by CCl(4), and the closest or most suitable animal model for damp-heat jaundice syndrome may be the one induced by CCl(4).

Inhibition of hepatic stellate cell activation following Yinchenhao decoction administration to dimethylnitrosamine‐treated rats

In an effort to investigate the mechanism by which Yinchenhao decoction (YCHD) acts on liver injury, we investigated the potential antifibrogenic effects of YCHD in an experimental liver fibrosis rat model, with special focus on the mechanisms inhibiting the activation and promoting apoptosis of hepatic stellate cells (HSC). The rats were initially randomized into two groups: the control (n = 10) and dimethylnitrosamine-treated (DMN; n = 30) groups. DMN (10 mg/kg body weight) was administered intraperitoneally to the DMN-treated rats for three consecutive days each week. At the end of the second week, three rats from the control and six rats from the DMN-treated groups were killed for the fibrosis development assessment. The remaining DMN rats were further randomized into two groups: the DMN-water group (n = 12) and the DMN-YCHD group (n = 12). Both groups continued to receive weekly DMN treatment for another 2 weeks in addition to daily administration of either water or YCHD, which were given intragastrically at a dose of 0.418 g/100 g body weight. Hepatic hydroxyproline content decreased and had improved histopathology in the DMN-YCHD rats. Compared to the DMN group, alpha-smooth muscle actin (SMA) and CD68 expression in the DMN-YCHD group was reduced significantly; however, alpha-SMA-positive HSC apoptosis was not observed by confocal microscopy; Fibrogenic proteins (tissue inhibitor matrix proteinases-1 and 2 and matrix metalloproteinase [MMP]-2/14) and cytokines (tumor necrosis factor-alpha and transforming growth factor-beta(1)) were decreased; MMP-9 was significantly upregulated. Yinchenhao administration attenuates liver fibrosis at least in part by inhibiting HSC activation directly, rather than promoting cell apoptosis of activated HSC, and the suppressive activation of Kupffer cells.