Total Flavonoids from Flowers of Abelmoschus manihot for Amelioration of α-naphthylisothiocyanate-induced Cholestasis by Regulating Expression of Transporters

Objective To explore the molecular mechanisms of the total flavonoids extracted from the flowers of Abelmoschus manihot(TFA) against α-naphthylisothiocyanate(ANIT)-induced cholestasis. Methods The hepatoprotective activities of TFA(125, 250 and 500 mg/kg) were investigated on ANIT-induced cholestatic liver injury in rats. Serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), total bile acid(TBA), and bile flow were measured to evaluate the protective effect of TFA. Furthermore, the hepatic m RNA and protein levels of transports, multidrug resistance-associated protein 2(MRP2), bile salt export pump(BSEP), and Na+-taurocholate cotransporting polypeptide(NTCP) were investigated to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. Results Pretreatment of TFA significantly and dose-dependently decreased the ANIT-induced elevation of serum ALT, AST, TBIL, and TBA levels and increased the ANIT-induced suppression of bile flow. Moreover, TFA was found to increase the expression of liver MRP2, BSEP, and NTCP in both protein and m RNA levels in ANIT-induced liver injury in rats with cholestasis. Conclusion TFA exerts a therapeutic effect on ANIT-induced liver injury in rats with cholestasis, possibly through regulating the expressions of hepatic transporters.     

Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts

The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts（AME）. In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride（CCl4）-induced hepatitis in mice, D-galactosamine（D-GalN）-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.     

Hepatoprotective Effects of Yintian Granule on Experimental Liver Injury in Mice

Objective Yintian Granule (YTG), as a type of local preparation and applied for Chinese patent, is mainly composed of several traditional Chinese herbs used as both drug and food such as Lonicera macranthoides, Gardenia jasminoides, and Asparagus cochinchinenis, and has been reported to demonstrate the beneficial effects on human health in other researches. In this paper, the protective effects of YTG against experimental acute liver injury of mice were investigated to assess the value of this innovative Chinese herbal compound. Methods Carbon tetrachloride (CCl4) and 50% ethanol were used respectively to induce the acute liver injury model in mice pre- administered with YTG. Lai’s method was used to detect the level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, Coomassie brilliant blue method was used for the determination of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, and hematoxylin-eosin (HE) staining was used for the observation of liver histomorphometry. Results YTG significantly lowered the elevated ALT and AST levels, increased the SOD activity, decreased the MDA content, and inhibited the deterioration of liver. Conclusion YTG exerts protective effected against hepatocyte damage in mice induced by CCl4 and 50% ethanol, respectively.     

Effects of total iridoid glycosides of Picrorhiza scrophulariiflora against non-alcoholic steatohepatitis rats induced by high-fat and high-sugar diet through regulation of lipid metabolism

Objective： To investigate the therapeutic effect of total iridoid glycosides of Picrorhiza scrophulariiflora (TIGP) on non-alcoholic steatohepatitis (NASH). Methods： SD rats were fed with high-fat and high-sugar diet for 8 weeks to establish NASH. TIGP were given orally at doses of 20, 40 and 80 mg/kg/d for 4 weeks. Triglycerides assay (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting plasma glucose (FPG), fasting insulin (FINS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), chemokine-1 (MCP-1), leptin (LEP) in serum were tested. TG, TC, superoxide dismutase (SOD), malondialdehyde (MDA), and free fatty acid (FFA) in liver tissue were determined by colorimetric methods. Steatosis of hepatocytes and inflammation was performed by pathological examination. Results： The results showed that TIGP significantly decreased TC, TG and FFA in liver tissue, increase SOD activity, decreased MDA content, decreased serum levels of TG, TC, HDL-C/LDL-C, ALT, AST, GLU, HOMA-IR, TNF-? and LEP, and in addition, improved steatosis of liver cells compared to NASH. Conclusion： TIGP had anti-fatty liver effect against high-fat and high-sugar diet induced NASH rats. Its mechanism was related to the regulation of lipid metabolism and reduction of insulin resistance, through inhibition of oxidative stress and inflammation.     

Protection of Citrullus colocynthis Fruit Extracts on Carbon Tetrachloride-induced and Bacillus Calmette-Guerin plus Lipopolysaccharide-induced Hepatotoxicity in Mice

Objective To investigate the hepatoprotective activities of the extracts from Citrullus colocynthis(ECC),a native plant used as traditional Uigur Medicine on acute liver injury in mice.Methods The activities of ECC of petroleum ether(ECCPE),chloroform(ECCC),ethyl acetate(ECCEA),n-butyl alcohol(ECCBA),and water(ECCW)were evaluated in vivo using two experimental models,carbon tetrachloride(CCl4)-and bacillus calmette-guerin(BCG)plus lipopolysaccharide(LPS)-induced acute hepatotoxicity in mice.The contents of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in serum were determined and the liver histological examination was carried out,respectively.Results The pretreatment with ECC for 7 d obviously reduced the impact of CCl4toxicity on the serum markers of liver damage,ECCEA and ECCC with a significant difference of AST(P<0.01,0.05,respectively)and ALT(P<0.05,0.01,respectively).The protective activity was reconfirmed against BCG+LPS-induced injury and the serum enzymatic levels were obviously elevated,for ECCEA and ECCC with a significant difference of AST(P<0.05,0.01,respectively)and ALT(P<0.01,0.05,respectively).Conclusion That ECCEA and ECCC are the potent hepatoprotective extracts that could protect liver against the acute injury,and this ability might be attributed to their hepatoprotective potentials.     

Effects of total iridoid glycosides of Picrorhiza scrophulariiflora against non-alcoholic steatohepatitis rats induced by high-fat and high-sugar diet through regulation of lipid metabolism

Objective: To investigate the therapeutic effect of total iridoid glycosides of Picrorhiza scrophulariiflora(TIGP) on non-alcoholic steatohepatitis(NASH).Methods: SD rats were fed with high-fat and high-sugar diet for 8 weeks to establish NASH. TIGP were given orally at doses of 20, 40 and 80 mg/kg/d for 4 weeks. Triglycerides assay(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), aspartate aminotransferase(AST), alanine aminotransferase(ALT), fasting plasma glucose(FPG), fasting insulin(FINS), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), chemokine-1(MCP-1), leptin(LEP) in serum were tested. TG, TC, superoxide dismutase(SOD), malondialdehyde(MDA), and free fatty acid(FFA) in liver tissue were determined by colorimetric methods. Steatosis of hepatocytes and inflammation was performed by pathological examination.Results: The results showed that TIGP significantly decreased TC, TG and FFA in liver tissue, increased SOD activity, decreased MDA content, decreased serum levels of TG, TC, HDL-C/LDL-C, ALT, AST, GLU,HOMA-IR, TNF-α and LEP, and in addition, improved steatosis of liver cells compared to NASH.Conclusion: TIGP had anti-fatty liver effect against NASH rats induced by high-fat and high-sugar diet. Its mechanism was related to the regulation of lipid metabolism and reduction of insulin resistance, through inhibition of oxidative stress and inflammation.     

圆果荨麻叶提取物对大鼠阿霉素心脏毒性的心肌保护作用(英文)

AIM:The present study evaluated the cardioprotective property of the hydroethanol extract of Urtica parviflora leaf material(EEUP) against doxorubicin-induced cardiotoxicity in rats.METHODS:Cardiotoxicity was produced by doxorubicin ad-ministration(15 mg·kg-1 i.p.for 21 days).The rats received EEUP at 200 and 400 mg?kg-1 b.w.(i.p.) daily for 21 days.After 24 h,serum cardiac biomarkers,i.e.creatine phosphokinase(CPK) and lactate dehydrogenase(LDH);serum lipid profiles,like high density lipoprotein(HDL),low density lipoprotein(LDL) and triglyceride(TG);serum biochemical parameters,viz.aspartate aminotransferase(AST),alanine transaminase(ALT) and alkaline phosphatase(ALP);myocardial antioxidant parameters,viz.malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT) and reduced glutathione(GSH) were measured.RESULTS:EEUP treatment significantly(P < 0.01) and dose dependently protected the myocardium by decreasing the elevated level of MDA;elevating the diminished levels of GSH,SOD,CAT and HDL,with a concomitant decrease in the elevated levels of HDL,LDL,and TG.EEUP also significantly(P < 0.01) reduced the increased activities of AST,ALT,ALP,CPK and LDH.The results revealed that EEUP demonstrated dose dependent cardioprotective efficacy by restoration of the serum biomarkers profile and antioxidant property.CONCLUSION:From the present study,U.parviflora leaf extract showed promising cardioprotective effect against doxorubicin-induced cardiotoxicity in Wistar rats.     

Mitochondria are Main Targets of Time/Dose‑Dependent Oxidative Damage‑Based Hepatotoxicity Caused by Rhizoma Dioscoreae Bulbiferae in Mice

Background: Rhizoma Dioscoreae bulbiferae could cause liver damage, which limited its application in the clinic. Aims and Objectives: To explore the mechanism of hepatotoxicity of Rhizoma Dioscoreae bulbiferae in mice. Materials and Methods: In the present study, the water extraction of Rhizoma Dioscoreae bulbiferae (W.E.R) was administrated via intragastrical with Low (19.6 g/kg), Middle (28.0 g/kg), and High (40.0 g/kg) dose in mice. At each time point 14 days, 21 days, and 28 days, the body weight, liver coefficient, indexes of liver function alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate transaminase (AST), various biochemical biomarkers of liver tissue and mitochondria were detected and analyzed. Results: We found that W.E.R could decrease the body weight, increase the liver coefficient and the expression levels of indexes of liver function in mice. Next, we investigated that W.E.R could increase the expression levels of reactive oxygen species (ROS) and malondialdehyde (MDA), decrease the expression levels of adenosine triphosphate (ATP) and improve the enzyme activities of total superoxide dismutase (SOD). Third, we found that W. E. R could increase the enzyme activities of manganese-superoxide dismutase, decrease the enzyme activities of sodium-potassium adenosine triphosphatase (Na + -K + -ATPase) and calcium-magnesium adenosine triphosphatase (Ca 2+ -Mg 2+ -ATPase). Finally, we analyzed that there were significant negative correlations between body weight, expression level of ATP, activity of Na + -K + ?ATPase, activity of Ca 2+ -Mg 2+ ?ATPase and time, dose. There were significant positive correlations between liver coefficient, ALP, ALT, AST, expression levels of ROS, MDA and time, dose. Conclusion: All the results above indicated that W.E.R could cause the hepatotoxicity based on the oxidative damage in mice, which and mitochondria might be the main targets.     

Hepatoprotective activity of Gentiana veitchiorum Hemsl. against against carbon tetrachloride-induced hepatotoxicity in mice

AIM： To study the hepatoprotective effect of methanol extract of Gentiana veitchiorum （MGV） against CCl4-induced oxidative stress and liver injury in mice. METHOD： The acute hepatic model was developed by injection of 20% CCh in mice. ICR mice were divided into six groups, including control, CCl4, CCl4＋ silymarin, and CCl4 MGV （100, 200, and 400 mg.kg^＆-1） groups. Hepatic enzymes including AST, ALT and ALP levels in serum, and antioxidant enzymes, including SOD, CAT and GPX activity in liver tissue, were determined. Histopathological examination and Western blot analysis were performed. RESULTS： Oral administration of MGV at 200 and 400 mg.kg-1 for 15 days dose-dependently inhibited the serum elevations of AST, ALT, and ALP, and recovered the reduction of SOD, CAT, and GPX in liver tissue. Hematoxylin and eosin staining examina- tion performed in liver tissues suggested that MGV treatment ameliorated histopathological changes in CCl4-induced mice. Westem blotting analysis implied that MGV increased HO-1 expression and recovered TNF-α alternation. CONCLUSION： G veitchiorum can protect the liver against CCl4-induced damage in mice, and this hepatoprotective effect was due at least in part to its ability through scavenging CCl4-associated free radical activities. The study provided in vivo evidence that G veitchiorum can be used as a safe, cheap, and effective agent to reduce acute liver damage, supporting its folk medicine use.     

白藜芦醇对急性化学性肝损伤保护机制的实验研究

目的：探讨白藜芦醇对四氯化碳（CCL4）诱导小鼠急性肝损伤保护作用的机制。方法：建立CCL4诱导小鼠急性肝损伤模型,以血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）活性;白细胞介素-6（IL-6）含量;肝匀浆丙二醛（MDA）含量及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）、过氧化氢酶（CAT）活性为检测指标,观察白藜芦醇对实验性肝损伤保护作用的机制。结果：白藜芦醇呈剂量依赖性降低CCL4小鼠血清中ALT、AST活性,降低肝匀浆MDA含量,提高肝匀浆SOD、GSH-PX、CAT活性,降低血清中IL-6水平。结论：白藜芦醇可通过抗氧化作用及抑制IL-6表达而产生对肝脏的保护作用。     

甘草提取物对小鼠四氯化碳急性肝损伤的影响

目的探讨甘草提取物对四氯化碳（CC14）所致小鼠急性化学性肝损伤的保护作用。方法采用CC14制备小鼠急性化学性肝损伤模型,50只小鼠随机分成5组：正常对照组、CC14模型组、联苯双酯组及甘草提取物小、大剂量组。各给药组连续给药7d,测定血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）、总蛋白（TP）活性及白蛋白（ALB）、球蛋白（GLB）的含量,以及肝组织中过氧化物歧化酶（SOD）、丙二醛（MDA）的含量。结果甘草提取物能明显降低CC14致急性肝损伤小鼠血清ALT、AST活性,降低肝匀浆中MDA含量,提高SOD活性。结论甘草对CC14所致小鼠急性化学性肝损伤的保护作用可能与其抗脂质过氧化有关。     

肝酶灵注射液对大鼠慢性肝损伤的保护作用

目的：观察肝酶灵注射液对大鼠慢性肝损伤的保护作用。方法：采用颈后皮下注射CCl4致大鼠慢性肝损伤为模型，测定肝酶灵注射液对肝损伤大鼠AST、ALT、ALP和白蛋白／球蛋白的影响，同时对肝组织进行病理组织学检查。结果：肝酶灵注射液能降低慢性肝损伤大鼠血清AST、ALT、ALP含量，升高白蛋白／球蛋白，减轻肝组织的病理变化，保护肝组织的超微结构。结论：肝酶灵注射液对大鼠慢性肝损伤有显著的保护作用。     

灵芪蠲肝液对大鼠慢性肝损伤氧自由基和一氧化氮的影响

目的通过动物实验研究灵芪蠲肝液对慢性肝损伤的防治机理。方法用40%的四氯化碳溶液复制慢性肝损伤模型,取血测定肝功能,血清NO,MDA和SOD,10%肝匀浆的MDA、SOD,并取肝组织做病理学检查。结果四氯化碳慢性肝损伤时,灵芪蠲肝液可降低ALT,AST,MDA,NO,升高ALB及SOD水平,促进肝细胞再生。结论灵芪蠲肝液能减少慢性肝损伤氧自由基和NO,调节蛋白质代谢。     

4-乙酰氧基苯并恶唑-2-酮对小鼠急性肝损伤的保护用

目的研究4-乙酰氧基苯并恶唑-2-酮(AcO-BOA)对四氯化碳小鼠急性肝损伤的保护作用。方法用腹腔注射四氯化碳(Carbon tetrachloride,CCl4)造小鼠急性肝损伤模型后,给予不同剂量的AcO-BOA,检测血清中的丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性,肝组织中的超氧化物歧化酶(SOD),还原型谷胱甘肽(GSH)活性以及丙二醛(MDA)含量。结果 AcO-BOA能升高肝组织中的SOD,GSH活性,明显降低血清中的ALT、AST的活性和肝匀浆的MDA含量(P<0.05)。结论 4-乙酰氧基苯并恶唑-2-酮能降低肝损伤的程度,对四氯化碳导致小鼠急性肝纤维化有一定的保护作用。     

复方蜂胶片对化学性肝损伤保护作用的研究

目的 :研究复方蜂胶片对化学性肝损伤是否具有保护作用并探讨其可能的保护作用机制。方法 :采用CCL4急性染毒来建立化学性肝损伤大鼠模型 ,并将复方蜂胶片以 2个剂量 (1.4 4、0 .72 g生药 /kg)经口灌胃给药 ,每天 1次 ,连续 12天 ,最后进行血清生化指标和肝脏组织病理学等项目检测以及体内肝脏抗氧化实验。结果 :模型组相比 ,高剂量组的ALT、AST以及ALP活性显著性降低 (P <0 .0 0 1) ,及TBA含量显著性降低 (P <0 .0 0 1) ,肝脏组织结构病理损害明显改善 ,肝脏MDA水平显著降低 ,SOD和GSH -PX活性明显升高。结论 :复方蜂胶片对CCL4所致化学性肝损伤具有保护作用 ,其保护机制可能主要为 :清除自由基和抑制脂质过氧化作用。     

藏药郎庆阿塔治疗肝纤维化的实验研究

目的:研究藏药郎庆阿塔对复合因素所致大鼠肝纤维化的治疗作用.方法:清洁级Wistar大鼠90只采用复合因素(高脂低蛋白饲料喂养、含乙醇饮用水加皮下注射四氯化碳)制备大鼠肝纤维化模型,造模6周末随机处死12其造模大鼠,通过肝组织病理检查及血清肝功能指标来检查肝纤维化模型成功率.将模型大鼠随机分为模型对照组、阳性药复方鳖甲软肝片组(0.55 g·kg-1)、郎庆阿塔颗粒给药高、中、低剂量组(生药11.4,5.7,2.85 g·kg-1),另设正常对照组.各组大鼠于分组后即日(第7周)开始ig给药,每日1次,连续ig给药7周.治疗结束后,检测血清中生化指标和肝纤维化指标,并取肝脏组织,测定肝脏组织中羟脯氧酸含量、超氧化物歧化酶(SOD)活力及丙二醛(MDA)水平,另取肝脏组织标本进行病理组织学检查.结果:郎庆阿塔能明显降低肝纤维化大鼠增高的肝脏系数和肝组织中羟脯氨酸含量(P ＜0.05～p＜0.01),显著降低肝纤维化大鼠血清中异常升高的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、总胆红素(T-BIL)、透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原氨端肽( PⅢ NP)及Ⅳ型胶原(CⅣ)(P＜0.05～P＜0.01),升高白蛋白(ALB)和A/G,比值,能明显升高肝组织中SOD活力(P＜0.05～P＜0.01)、降低异常升高的MDA水平(P ＜0.05～P＜0.01),病理组织学检查结果表明郎庆阿塔高、中剂量对肝纤维化大鼠肝纤维组织增生、肝组织炎症活动度均有显著的改善作用(P ＜0.05～P＜0.01),并能显著降低肝组织中胶原纤维面积(P＜0.05～P＜0.01).结论:藏药郎庆阿塔具有明显的治疗肝纤维化作用.     

经方四逆散对肝损害的保护作用及机制研究

[目的]观察经方四逆散对肝损害的保护作用及机制研究。[方法]采用石胆酸灌胃造成肝损害，检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平，并作肝组织病理学观察。[结果]经方四逆散能降低石胆酸灌胃造成肝损害小鼠血清ALT、AST、MDA升高的水平，能升高石胆酸灌胃造成肝损害小鼠血清SOD、GSH降低的水平；经方四逆散能使肝损害小鼠肝组织病理变化程度明显减轻。四逆散药粉 米汤降AST、MDA明显，四逆散煎剂降ALT明显。[结论]经方四逆散具有一定的保肝作用。     

薰衣草醇提物对小鼠急性肝损伤保护作用的研究

目的：研究薰衣草醇提物对四氯化碳（CCl4）所致小鼠急性化学性肝损伤的保护作用。方法：利用CCl4制作小鼠急性化学性肝损伤模型,灌胃给予小鼠薰衣草醇提物。测定小鼠丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）,超氧化物歧化酶（SOD）活性,丙二醛（MDA）含量。结果：薰衣草醇提物各剂量组均能升高急性化学性肝损伤小鼠血清AIT和AST活性（P〈0．01）,升高肝组织SOD活性（P〈0．01）,降低MDA含量（P〈0．01）。结论：薰衣草醇提物对CCl4所致急性化学性肝损伤具有保护作用。     

护肝解毒冲剂的抗肝损伤作用研究

目的观察护肝解毒冲剂的抗肝损伤作用。方法用D-半乳糖胺(D-GaLN)复制急性肝损伤模型;采用四氯化碳(CC l4)诱导慢性肝损伤模型。实验结束时分别取血测ALT,AST活性和总蛋白(TP),白蛋白(ALB),白/球比例(A/G),透明质酸(HA),同时均取肝组织做病理检查。结果急性肝损伤时,护肝解毒冲剂能降低ALT,AST活性及减轻肝细胞坏死及炎细胞浸润;慢性肝损伤时,其能降低ALT,AST和HA,升高TP,ALB和A/G,并减轻肝细胞变性,减少纤维组织增生。结论护肝解毒冲剂对大鼠D-GaLN所致急性肝损伤和CC l4所致慢性肝损伤均具有保护作用。