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

Objective:To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine.Methods:The liver injury in the model rat was induced byα-naphthylisothiocyanate(ANIT) and carbon tetrachloride(CCl_4) respectively,and the effects of Yinchenhao Decoction(茵陈蒿汤,YCHD),a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic,on the two liver injury models were evalu...     

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

<正>Objective: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(茵陈蒿汤,YCHD) using an ultra pressure liquid chromatography(UPLC) method.Methods: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.Results: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 4.533μg/mL and 6.885μg/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)(P0.05),but there showed a 45.52%and 92.93%reduction in clearance of drug and volum of distribution(P0.05),respectively.Conclusions: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.     

Effects of Modified Sanhuang Decoction (加味三黄汤) Enema on Serum Tumor Necrosis Factor-α and Colonic Mucosa Interleukin-1β, Interleukin-6 Levels in Ulcerative Colitis Rats

Objective:To investigate the effects of Modified Sanhuang Decoction(加味三黄汤,MSD)enema on the serum tumor necrosis factor alpha(TNF-α)and colonic mucosa interleukin-1β(IL-1β),interleukin-6(IL-6)levels in experimental ulcerative colitis(UC)rats.Methods:Forty-five male Wistar rats were randomly divided into 4 groups:normal group(n=12),model group(n=11),salazosulfapyridine(SASP)group(n=11)and MSD group(n=11).The UC model was induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS)/ethanol solution.Rats in the normal group and model group were clystered with 0.9%normal saline,while in the SASP group and MSD group were clystered with SASP and MSD enema,respectively.After drug administration(10 mL/kg body weight,for 7 days),colonic gross changes and colonic mucosa histology were observed,serum TNF-αand colonic mucosa IL-1β,IL-6 levels were tested by enzyme linked immunosorbent assay and radioimmunoassay,respectively.Results:As compared with the normal group,the experimental UC rats,the colonic mucosal damage index scores(CMDIs),histopathological scores(HS)and the serum TNF-a and colonic mucosa IL-1β,IL-6 levels significantly increased(P0.05 or P0.01).In the MSD and SASP groups,the ulcer area significantly reduced,and edema disappeared.The CMDIs,HS,the serum TNF-a and colonic mucosa IL-1β,IL-6 levels in the MSD and SASP groups significantly decreased(P0.05 or P0.01)compared with the model group.The CMDIs in the MSD group were lower than that in the SASP group(P0.05),but there were no significant differences in HS,serum TNF-αor colonic mucosa IL-1β,IL-6 levels between the MSD and SASP groups.Conclusion:MSD enema can improve colonic mucosa impairment and decrease serum TNF-αand colonic mucosa IL-1β,IL-6 levels in experimental UC.     

Inhibitory Effect of Oxymatrine on Quartz-induced Secretion of TNF-α by the Pulmonary Alveolar Macrophages in the Fibroblast Proliferation

The massive proliferation of pulmonary fibroblasts is the common consequence shared by lung diseases. The over-expression of TNF-α plays an important role in the proliferation of pulmonary fibroblasts[1, 2]. Under patho-logical conditions, TNF-α is predominantly secreted by activated alveolar macrophages of lung. The high level of TNF-α acts on the receptors on the cell membrane of fibroblasts, mediates the conduction of intracellular sig-nals and eventually activates the nuclear factor…     

The effect of spinal cord injury on the expression of TGF-β and TNF-α in rat articular cartilage

Objective: To observe the expression of TGF-β and TNF-α in the spinal cord injured rat model and discuss the significance of the articular cartilage metabolism. Methods: 36 SD female rats were randomly divided into 2 groups: Rats models of spinal cord injury were implemented by Allen method. T10 laminectomy was performed in the control group. Both groups of rats were killed respectively in 1w, 3w and 6w. Hematoxylin-eosin stain was given to each slice in the model group and control group. Immunohistochemical stain was applied by using ABC method in the expression of TGF-β and TNF-α. Those expressed level were performed in image analysis and statistics process. Results: TGF-β and TNF-α were mainly distributed on the surface layer of the articular cartilage, with a weak expression in control group. The expression of TNF-α in the model group was more significant than that in the control group in the 1w, and still remained an evident difference with that in control group until the 6w(P ＜ 0.05). TGF-β expression of the model group had no remarkable difference with the control group in the lw (P ＞ 0.05) and prominently became stronger at 6w(P ＜ 0.05). Conclusion: The expression of TNF-o occurred early in the development of spinal cord injury, and the expression of TGF-β became stronger with the revival of spinal neural function. Both expressions were strengthened in articular cartilage in the 3rd week.     

Effect of Salvia Miltiorrhiza Bge on Left Ventricular Hypertrophy and the Expression of Tumor Necrosis Factor-α in Spontaneously Hypertensive Rats

The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechanism were investigated. Normal Wistar-kyoto (WKY) rats were used as negative control, and spontaneously hypertensive rats (SHR) were randomly assigned to receive pla- cebo or SMB. SMB (1 g/kg·d) was injected intraperitoneally for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured. HE, VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size, diameter, the collagen volume fraction (CVF), perivascular circumferential area (PVCA), and tumor necrosis factor-α (TNF-α) expression in the left ventricular tissue. The results showed, as compared with WKY rats, the SBP, LVMI, cardiomyocyte size, diameter, CVF, PCVA, and TNF-α expression were increased markedly in the 20-week-old spontaneously hypertensive rats. SMB decreased LVMI (P<0.01), size of cardiomyocytes (P<0.01), collagen volume fraction (P<0.01), perivascular circum- ferential area (P<0.01), and TNF-α expression (P<0.01), but had no effect on SBP (P>0.05). It was suggested that chronic administration of SMB could inhibit and reverse the development of LVH in spontaneously hypertensive rats independent of BP. TNF-α may be involved in the reversal mecha- nism of LVH by SMB.     

Effect of Tumor Necrosis Factor-αon Resistin Expression in 3T3-L1 Adipocytes and Its Mechanism

Insulin resistance plays an important role inthe pathogenesis, development and complication indiabetes mellitus. Obesity is one important cause,but its mechanism is complicated. Steppan foundthat resistin had direct effect on insulin in mouseadipose cells in 2001 and believed that it might bethe key molecule of diabetes mellitus[1]. TNFαis apolypeptide which has extensive biological actionand effects in the development of anti tumourmechanism, immunoloregulati…     

Effect of Reduqing (热毒清) on Endotoxin-Induced Production of Tissue Factor and Cytokines in Human Whole Blood

lipopolysaccharide,monocytes,mononuclearcellsReduqinginjection(RDQ,originallynamedAnti--inflammatoryAgentNo.6)isamodernChineseherbalpreparationmodifiedfromtherepresentativedecoctionWuweiXiaoduYin(Eapi6$ts).ItconsistsofextractedmaterialsfromFlosLonicerae,Foliumlsatidis,HerbaTaraxaci,andHerbaHouttuyniae,andbelongstothe"heat--clearinganddetoxifying"categoryofChinesemedicine.Inthepasttwodecades,RDQInfectionhadbeenusedinanumberofChinesehospitalsforthetreatmentofacuteabdomenandotheracuteinf…     

Effects of Danggui Buxue Decoction (当归补血汤) on lipid peroxidation and MMP-2/9 activities of fibrotic liver in rats

Objective:To explore the mechanism of Danggui Buxue Decoction(当归补血汤,DBD) on the liver fibrosis related to hepatic lipid peroxidation and matrix metalloproteinases(MMP) -2/9 activities.Methods: The liver fibrosis in 28 rats was induced by an injection of carbon tetrachloride(CCl_4) and fed with high lipid and low protein diet for 6 weeks,the model rats were randomly divided into the model group and DBD treated group,14 in each group,and another 10 rats as the normal group were observed as well.Rats in the...     

Effects of Electroacupuncture at Shangjuxu (ST 37) on Interleukin-1βand Interleukin-4 in the Ulcerative Colitis Model Rats

To probe into the mechanisms of electroacupuncture (EA) at Shangjuxu (ST 37) for treatment of the ulcerative colitis (UC). Methods: Forty male Wistar rats were randomly divided into 4 groups: a normal group,a model group,a Shangjuxu group and a non-acupoint group,10 rats in each group. The UC rat model was made with enema of trinitro-benzenesulfonic acid (TNBSA),and the changes of interleukin-1β (IL-1β) and interleukin-4 (IL-4) contents after EA at Shangjuxu (ST 37) were observed. Results: EA at Shangjuxu (ST 37) could significantly decrease the IL-1β content and increase the IL-4 content in the colic tissues of the UC rats with significant differences as compared with the model group and the non-acupoint group (P<0.05 or P<0.01). Conclusion: The mechanisms of EA at Shangjuxu (ST 37) for treatment of the UC rats is possibly related with the decrease of IL-1β,a inflammation-promoting cytokine,and the increase of IL-4,a anti-inflammatory cytokine.     

Effect of Buyang Huanwu Decoction (补阳还五汤) on Plasma Thromboxane B_2, 6-Keto-Prostaglandin F_(1α), Endothelin and Calcitonin Gene Related Peptide in Primary Nephrotic Syndrome Patients

ＴｈｅｆｕｎｃｔｉｏｎｏｆｔｈｒｏｍｂｏｘａｎｅＢ2 （ＴＸＢ2 ）,6 ｋｅｔｏ ｐｒｏｓｔａｇｌａｎｄｉｎＦ1α （ 6 Ｋ ＰＧＦ1α）,ｅｎ ｄｏｔｈｅｌｉｎ（ＥＴ）ａｎｄｃａｌｃｉｔｏｎｉｎｇｅｎｅｒｅｌａｔｅｄｐｅｐ ｔｉｄｅ（ＣＧＲＰ）ｉｎｇｌｏｍｅｒｕｌｏｐａｔｈｙｈａｖｅａｌｒｅａｄｙａｒｏｕｓｅｄｉｎｔｅｒｓｔｏｆｃｌｉｎｉｃｉａｎｓ．（1 - 3） Ｓｉｎｃｅ 1 995,ｗｅｕｓｅｄＢｕｙａｎｇＨｕａｎｗｕＤｅｃｏｃｔｉｏｎ（补阳还五汤,ＢＹＨＷＤ）ａｓａｎｔｉｃｏａｇｕｌａｎｔｉｎｔｒｅａｔｉｎｇ…     

Effects on the Tumor Specific Growth Factor and Tumor Necrosis Factor α in Rats' Precancerous Lesion of Primary Hepatocellular Carcinoma by Direct Moxibustion at Ganshu(BL 18) Acupoint

Objective: To investigate the effect of direct moxibustion at Ganshu(BL18) on the serum concentrations of tumor specific growth factor(TSGF) and tumor necrosis factor α(TNF-α) in a rat model with precancerous lesion of primary hepatocellular carcinoma(HCC), so as to explore the mechanism of moxibustion underlying improvement of HCC. Methods: Sixty male Wistar rats were randomly divided into control group(n=10), model group(n=20), prevention group 1(n=15) and prevention group 2(n=15). The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibustion with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1(1 treatment course, 20 days) and prevention group 2(2 treatment courses, 40 days), 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point(before model establishment, the end of 1st course prevention, the end of 2nd course prevention and the end of model establishment), serum levels of TSGF and TNF-α were detected using enzyme-linked immunosorbent assay. Results: Compared with the control group, there was a remarkably increase of serum TSGF and TNF-α contents in the model group at the end of the experiment(P0.05). At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF-α of rats in the prevention group 1 were significantly increased compared with that of the model group(P0.05). At the end of the 2nd course of direct moxibustion, serum TSGF and TNF-α levels of rats in the model group were higher than the normal group with significantly difference(P0.05), and the levels of TSGF and TNF-α in the prevention group 2 were significantly reduced in comparison with the model group(P0.05). Conclusion: It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the therapeutic effect of two courses were better than one course.     

Study on the Analgesic Effect and Mechanism of Zhitong Capsule (止痛胶囊) in Adjuvant Arthritis Rats

Clinical practice has proved that traditionalChinese medicine (TCM) has a preferable effect ofrelieving pain, and has been widely used in treat ment of patients with pain symptoms. Basing uponthis, we formulated a recipe Zhitong Capsule(止痛胶囊, ZTC) consisting of multiple ingredients ofChinese medicinal herbs ( CMH). Our previousstudy(1,2) had showed that ZTC had a preferableeffect of analgesia and anti inflammation. In orderto further study its mechanism of a…     

Effects of Kaixin Jieyu Decoction (开心解郁汤) on Behavior and Glial Fibrillary Acidic Protein Expression in Cerebral Hippocampus of A Rat Vascular Depression Model

Objective:To explore the effects and anti-depression mechanisms of Kaixin Jieyu Decoction(开心解郁汤,KJD).Methods:The rat vascular depression(VD) model was established by ligation of bilateral common carotid arteries(LBCCA) combined with chronic unpredictable mild stress(CUMS).Forty Wistar rats were randomly divided into sham,VD model,VD + high-dose KJD[15.4 g/(kg·d) of crude drug],VD + medium-dose KJD[7.7 g/(kg·d) of crude drug],and VD + fluoxetine[2.4 mg/(kg·d)]groups(r=8 in each group),and the treatments lasted for 21 days.Changes of behavior and hippocampus pathology were observed.The level of glial fibrillary acidic protein(GFAP)protein and mRNA in hippocampus was detected respectively by immunohistochemistry and real-time polymerase chain reaction.Results:Compared with the sham group,rats in model group showed a variety of behavioral obstacles,including a significant reduction in sucrose consumption percentage,horizontal and vertical activity scores in open-field tests(P0.05 or P0.01),pathological damage like neuronal degeneration,necrosis,and a significant decrease of GFAP protein and mRNA in hippocampus(P0.01);compared with the model group,rats in the high-dose KJD group,medium-dose KJD group and fluoxetine group obtained notable higher behavioral scores,and pathological injury lessened in hippocampus with a increased expression of GFAP protein and mRNA(P0.05 or P0.01);compared with the medium-dose KJD group and fluoxetine group,GFAP mRNA in highdose KJD group expressed higer(P0.05).Conclusion:LBCCA combined with CUMS may cause depression-like behavioral changes resulting in the VD model of rats whose depression state can be ameliorated by KJD,and the mechanism of cerebral protection is related possibly with promoting expression of GFAP in hippocampus.     

Study on the Anti-Liver Fibrosis Effect of Benefit Liver Granule (益肝冲剂) and Its Mechanism in Rats

Ｉｎｒｅｃｅｎｔｙｅａｒｓ，ｓｔｕｄｉｅｓｏｎＣｈｉｎｅｓｅｍｅｄｉｃｉｎａｌｈｅｒｂｓｉｎ ｐｒｅｖｅｎｔｉｎｇａｎｄｔｒｅａｔｉｎｇｌｉｖｅｒｆｉｂｒｏｓｉｓｈａｖｅｐｒｏｌｉｆｅｒａｔｅｄ，ｂｕｔｆｅｗｄｅａｌｗｉｔｈｉｔｓｍｅｃｈａｎｉｓｍ．Ｔｒａ     

Effects of Wei Chang An pill(胃肠安丸) on enzyme activity and levels of vasoactive peptide and substance P in the small intestine of rats with compound diarrhea

OBJECTIVE:To investigate the regulatory effects of Wei Chang An Pill(WCAP) on enzyme activity and gastrointestinal hormones in the small intestine of rats with compound diarrhea.METHODS:Forty Wistar rats were randomly divided into a control,diarrhea model,and WCAP high,medium,and low dose groups.The control group was not treated,and the model group was administered intragastric distilled water.The WCAP groups were given WCAP suspension,80,60 or 40 mg · kg-1 · d-1,for 4 days.Stool properties were observed.After the experiment,thymus and spleen indices were measured,and the activities of lactate dehydrogenase(LDH),malate dehydrogenase(MDH),and disaccharidase(lactase) in the small intestinal mucous membrane,and levels of substance P(SP) and vasoactive peptide(VIP) in the colon were determined.RESULTS:Compared with the control group,thymus and spleen indices were significantly decreased,LDH,MDH,and disaccharidase activity in the small intestine was decreased,and SP and VIP levels in the colon were significantly increased inthe diarrhea model group.Compared with the model group,thymus and spleen indices were significantly increased,and LDH,MDH,and disaccharidase activity in the small intestine and SP and VIP levels in the colon were significantly decreased in theWCAP medium dose group.CONCLUSION:The diarrhea model rats exhibited pathological changes including atrophy of the thymus and spleen,decreased enzyme activity in the small intestine,and gastrointestinal hormone disturbance.WCAP can increase the activity of intestinal digestive enzymes and regulate gastrointestinal hormones,thereby relieving diarrhea.     

Effects of Tongmai Huoxue Yin(通脉活血饮) on Tumor Necrosis Factor-alpha in the Acute Cerebral Ischemia Model Rat

Objective:To observe the interfering action of Tongmai Huoxue Yin(通脉活血饮) on the acute cerebral ischemia model rat.Methods:Total 60 SD rats,30 females and 30 males,were randomly divided into 4 groups,sham-operation group,model group,Nimodipine group and Tongmai Huoxue Yin group,15 rats in each group.The acute cerebral ischemia rat model was duplicated,the middle cerebral artery(MCA) were ligated and the thread was inserted for the rats in the model group,Nimodipine group and Tongmai Huoxue Yin group,for the rats in the sham-operation group,the arteries were separated without ligature and the thread was not inserted.After the modeling has succeed,the water-decocted concentrated solution of 20-fold Tongmai Huoxue Yin clinical dosage was intragastrically administrated in a dose of 3 mL /100 g · d divided into twice,1.5 mL /100 g once.Distilled water 3 mL /100 g·d was intragastrically administrated,1.5 mL /100 g once,for the rat in the model group,Nimodipne suspension 3 mL /100 g·d(0.6 mg /100 g) for the Nimodipine group and 3 mL /100 g · d(5.4g /100 g) for the Tongmai Huoxue Yin group,no drugs for the sham-operation group.And changes of tumor necrosis factor-alpha(TNF-α) contents in the serum and brain tissue were investigated.Results:Compared with the model group,compared with the sham-operation group,serum TNF-α content at 5 h of focal cerebral ischemic ischemia in the model group started to increase and reached to the high peak at 12 h,but in both the Tongmai Huoxue Yin group and the Nimodipine group decreased in varying degrees at the same time;compared with the sham-operation group,brain TNF-α content at 6 h of focal cerebral ischemic ischemia in the model group started to increase and reached to the high peak at 12 h,but in both the Tongmai Huoxue Yin group and the Nimodipine group decreased in varying degrees,with the most obviously decreased at 24 h of ischemia.Tongmai Huoxue Yin could significantly decrease TNF-α content in the brain tissue.Conclusion:Tongmai Huoxue Yin has a protective action on acute cerebral ischemia injury in the rat.     

A Clinical Study on the Effects and Mechanism of Xuebijing Injection(血必净注射液)in Severe Pneumonia Patients

Objective: To observe the effects of Xuebijing Injection (血必净注射液) in patients with severe pneumonia, and to explore the mechanism. Methods: Eighty cases of severe pneumonia are randomly assigned to the Xuebijing treatment (forty cases) and the control group (forty cases), with the same routine therapy provided in both groups. Clinical effective rates, inflammatory factors and organ function were observed in both groups. Results: The effective rate was higher in Xuebijing group than that of the control group (80.0% vs. 67.5%, P<0.05). As compared with the control group, the LDH, α1-AG, α1-AT levels and the peak body temperature decreased markedly with the Xuebijing treatment going, and the secretion of TNF-α, IL-6, IL-8 was suppressed in Xuebijing group; but no significant difference was found in leptin level. Conclusion: Xuebijing Injection may show a protective effect in patients with severe pneumonia. The mechanism is possibly with the decreased secretion of TNF-α, IL-6, and IL-8.