Hypoglycemic, vasorelaxant and hepatoprotective effects of Cochlospermum vitifolium (Willd.) Sprengel: a potential agent for the treatment of metabolic syndrome

Cochlospermum vitifolium (Willd.) Sprengel is a Mexican medicinal plant that is used in the folk medicine for the treatment of hypertension, diabetes, hepatitis and related diseases. The purpose of the present study was to assess the pharmacological properties of different extracts from Cochlospermum vitifolium bark as potential agent for the treatment of some factors related with metabolic syndrome (MS), a complex disease produced for several pathophysiological factors such as visceral fat obesity, insulin resistance, hypertension, dyslipidemia and liver steatosis. Hexane (HECv), dichloromethane (DECv) and methanol (MECv) extracts were subjected to some pharmacological assays to determine their vasorelaxant and hypoglycemic activity. On the other hand, MECv was also evaluated to determine its hepatoprotective effect on sub-chronic experimental assay. HECv showed a significant endothelium-independent relaxation on rat aorta rings (intact endothelium: IC(50)=14.42+/-5.90 microg/mL, E(max)=92.71+/-8.9%; denuded endothelium: IC(50)=27.94+/-4.0 microg/mL, E(max)=78.68+/-4.6%) and MECv produced an endothelium-dependent relaxation (IC(50)=21.94+/-6.87 microg/mL, E(max)=79.12+/-7.80%) on this tissue. Furthermore, HECv (at a dose of 120 mg/kg) also showed a significant decrease of blood glucose levels (p<0.05) on normoglycemic rats. Moreover, MECv (at a dose of 100 mg/kg) also was administered to bile duct-obstructed rats to determine its hepatoprotective activity, showing a statistically significant decrease of serum glutamic-pyruvic transaminase (PGT, 45%) and alkaline phosphatase (APh, 15%) (p<0.05). Finally, we obtained a crystalline polyphenolic compound from MECv by spontaneous precipitation. Those crystals were identified as (+/-)-naringenin by X-ray diffraction, NMR, IR and GC-MS techniques. Results suggest that Cochlospermum vitifolium could be used as a potential agent against MS since it shows hypoglycemic, vasorelaxant and hepatoprotective properties.     

Protective effects of mycelia of Antrodia camphorata and Armillariella tabescens in submerged culture against ethanol-induced hepatic toxicity in rats

The hepatoprotective effects of the mycelia of Antrodia camphorata and Armillariella tabescens were evaluated in vivo using acute ethanol-intoxicated rats as an experimental model. Animals were orally treated with Antrodia camphorata (0.5 or 1.0 g/kg b.w.) or Armillariella tabescens (0.5 or 1.0 g/kg b.w.) for 10 days whereas controls received vehicle only. At the end of the experimental 10-day period, the animals were administered by gavage with an acute ethanol dose of 5.0 g/kg b.w. diluted in deionized water (6:4, v/v) and sacrificed at 18 h after ethanol administration. The degree of protection was measured by using biochemical parameters like serum transaminases (AST and ALT), alkaline phosphatase (ALP), bilirubin. Meanwhile, the histopathological studies were carried out to support the above parameters. Administration of Antrodia camphorata or Armillariella tabescens markedly prevented ethanol-induced elevation of levels of serum AST, ALT, ALP, and bilirubin comparable with standard drug silymarin.     

Hepatoprotective effect of Vitis vinifera L. leaves on carbon tetrachloride-induced acute liver damage in rats

The hepatoprotective effect of ethanolic extract and its four different fractions (CHCl(3), EtOAc, n-BuOH, and remaining water fraction) of Vitis vinifera L. leaves was investigated against carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. The ethanolic extract was found active at 125mg/kg dose (per os). The ethanolic extract was fractionated through successive solvent-solvent extractions and the n-BuOH fraction in 83mg/kg dose possessed remarkable antioxidant and hepatoprotective activities. Liver damage was assessed by using biochemical parameters (plasma and liver tissue MDA [malondialdehyde], transaminase enzyme levels in plasma [AST-aspartate transaminase, ALT-alanine transferase] and liver GSH [glutathione] levels). Additionally, the pathological changes in liver were evaluated by histopathological studies. Legalon 70 Protect was used as standard natural originated drug.     

Protective effects of chalcone derivatives for acute liver injury in mice

The hepatoprotective effects of chalcone derivatives were evaluated in D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced fulminant hepatic failure in mouse. Thirteen chalcone derivatives were synthesized for study and their hepatoprotective effects were evaluated by assessing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum. Chalcone preparations were injected into mice at 12 h and 1 h before intraperitoneal injection of D-GalN/LPS. After abdominal administration, changes in AST and ALT between the control and treated groups were observed. Ten of the synthesized chalcone derivatives exhibited inhibitory effects on D-GalN/LPS-induced levels of AST and ALT in mice. Compounds 2, 3, 8, 9, and 12 markedly reduced serum AST and ALT at 8 h, inhibited hepatocyte necrosis and showed significant hepatoprotective activities. The activity of compound 3 was compared with the bifendate (DDB) through oral administration. Compound 3 showed much higher inhibitory effects than bifendate for decreasing AST and ALT activity. The results indicate that compound 3 has strong hepatoprotective activity through suppression of tumor necrosis factor-alpha (TNF-alpha) preduction, reduction of the histological change in the liver, and attenuated of hepatocyte apoptosis confirmed by DNA fragmentation assay.     

Effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of organic cations (OCS): Selective inhibition of sinusoidal OCs uptake without influencing glucose uptake and canalicular OCs excretion

The effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of a model organic cation (OC), TBuMA (tributylmethylammonium), was investigated. The area under the plasma concentration-time curve (AUC) from time zero to 4 h following iv administration of TBuMA (6.6 micromol/kg) was increased significantly when YH-439 in corn oil (300 mg/kg) was orally administered to rats 24 h prior to the experiment. Nevertheless, the cumulative biliary excretion of TBuMA remained unchanged. As a consequence, the apparent biliary clearance (CLb) of TBuMA was decreased significantly as a result of YH-439 pretreatment, consistent with the fact that the in vivo excretion clearance of TBuMA across the canalicular membrane (CLexc) was not changed by the pretreatment. The in vitro uptake of TBuMA into isolated hepatocytes was decreased by one half by the pretreatment, owing to a decrease in the apparent Vmax and CLlinear, but the Km for the process remained constant. Most interestingly, however, the sinusoidal uptake of glucose, a nutrient, into hepatocytes was not influenced by the pretreatment, suggesting the YH-439 pretreatment specifically impaired the sinusoidal uptake of OCs. Thus, the OC-specific inhibition of hepatic uptake, without influencing the uptake of glucose, a nutrient, appeared to be associated with the hepatoprotective activity of YH-439.     

野山杏果肉总有机酸对高脂血症小鼠血脂及肝脏的影响

目的 研究野山杏果肉总有机酸(TOAWA)对高脂血症小鼠血脂的影响及其保肝作用.方法 ig给予小鼠高脂乳剂,建立小鼠高脂血症模型,每日ig给予小鼠不同剂量的TOAWA(0.1、0.2、0.4g·kg-1),连续4周,测定小鼠血清中总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)及三酰甘油(TG)的含量和肝脏匀浆液中超氧化歧化酶(SOD)、丙二醛(MDA)的水平,计算肝脏的脏器指数,观察肝脏组织的病理学变化.结果 TOAWA能显著降低小鼠血清中TC、LDL-C、TG的水平,升高HDL-C的含量,提高肝脏中SOD的活性,减少MDA的形成,同时降低肝脏的脏器指数;对高血脂症小鼠肝脏细胞的病理变化具明显的改善作用.结论 TOAWA能调节高血脂症小鼠的血脂水平,并具一定的保护肝脏和改善肝功能的作用.     

山苦荬保肝活性部位筛选及其化学成分研究

目的:筛选山苦荬保肝活性部位并对其化学成分进行研究。方法:采用系统溶剂法,以70%乙醇对山苦荬药材进行提取,用不同溶剂对所得提取物进行萃取,分别得石油醚、乙酸乙酯、正丁醇部位和剩余水部位。以对乙酰氨基酚诱导人肝细胞HL-7702复制肝损伤细胞模型,采用MTT法检测上述各部位(40μg/mL,均以生药量计)对损伤细胞的保护作用并筛选活性部位。采用硅胶柱、葡聚糖凝胶柱色谱等分离手段对活性部位进行分离纯化,根据理化性质和波谱(氢谱、碳谱)数据鉴定化合物结构。结果:经山苦荬不同萃取部位作用后,各药物组细胞的存活率均较模型组显著升高(P<0.01),其中正丁醇部位和水部位的活性最强(细胞存活率分别为49.3%、52.2%)。从正丁醇部位中共分离并鉴定出6个化合物,分别为苦荬菜木脂素A(Ⅰ)、芹菜素-7-O-β-D-吡喃葡萄糖醛酸苷甲酯(Ⅱ)、木犀草素7-O-β-D-吡喃葡萄糖醛酸苷甲酯(Ⅲ)、木犀草素-7-O-β-D-葡萄糖苷(Ⅳ)、芹菜素-7-O-β-D-葡萄糖苷(Ⅴ)和木犀草素(Ⅵ)。结论:山苦荬正丁醇部位为该药材的保肝活性部位之一,其活性成分以黄酮类化合物为主。     

Sasa quelpaertensis leaves ameliorate alcohol-induced liver injury by attenuating oxidative stress in HepG2 cells and mice

Oxidative stress plays a crucial role in the progression of alcoholic liver diseases and substances of antioxidant property are of special interest for therapeutic purposes. We investigated the hepatoprotective effect of leaf extracts of Sasa quelpaertensis, an edible bamboo mainly cultivated in Jeju Island, South Korea. We examined the cytotoxicity of different extracts (distilled water, 20–80% EtOH) of S. quelpaertensis on HepG2 cells and their hepatoprotective effect on HepG2 cells stimulated by ethanol (800?mM, 24?h). Furthermore, we measured reactive oxygen species (ROS) production, ethanol toxicity induced cell death, and the activity of antioxidant enzymes. In in vivo experiments, liver damage was induced by oral administration of 5?g/kg ethanol with or without potent ethanol extract of S. quelpaertensis (10 or 100?mg/kg) 12?h interval for a total of 3 doses. Only 80% ethanol extract of S. quelpaertensis (SQEE80) exhibited cytoprotective effect on HepG2 cells against alcohol-induced toxicity. SQEE80 treatment (250, 500?μg/mL) in ethanol exposed HepG2 cells showed significant attenuation of ROS production and ethanol toxicity induced cell death. Furthermore, SQEE80 markedly increased the activity of antioxidant enzyme glutathione peroxidase 1 in ethanol exposed HepG2 cells compared to ethanol stimulated cells. In in vivo experiments, SQEE80 treatment evidently suppressed the alcohol-induced histopathological changes in liver, serum ethanol content, and expression of cytochrome P450 2E1. Furthermore, SQEE80 significantly reversed the reduction of glutathione level in the ethanol challenged liver. Taken together, we suggest the possibility of developing SQEE80 as a natural hepatoprotective substance in attenuating alcohol-induced oxidative stress.     

Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat

AIM To evaluate the hepatoprotective effect of lycopene(Ly) on non-alcoholic fatty liver disease(NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglycerides(TG), total cholesterol(TC) in serum and low density lipoproteincholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), free fatty acid(FFA), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P450(CYP) 2E1 in rat liver were determined by immunohistochemistry analysis.RESULTS A significant decrease was observed in the levels of serum AST(2.07-fold), ALT(2.95-fold), and the blood lipid TG(2.34-fold) and TC(1.66-fold) in the dose of 20 mg/kg Ly-treated rats(P 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner,to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68(P 0.05, P 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased(P 0.05, P 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively(P 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C(P 0.05, P 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group(P 0.05, P 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all in a dosedependent manner(P 0.05, P 0.01). CONCLUSION This study suggests that Ly has a protective effect on NAFLD, down-regulates expression of TNF-α, and that CYP2E1 may be one of the action mechanisms for Ly.     

Hepatoprotective and antioxidant effects of baicalin against CCl4-induced hepatotoxicity

Scutellaria baicalensis is widely cultivated in eastern Asia, particularly in China. In the present study, we isolated baicalin from this plant and studied for its hepatoprotective activity against CCl₄-induced oxidative damage in rats. Our findings revealed that baicalin exhibited strong antioxidant activity in vitro. In established in vivo tests, baicalin showed effective protective effects by reducing the elevated levels of glutamate pyruvate transaminase(ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), total bilirubin (TB) and malondialdehyde (MDA) against CCl₄-induced damage, and it restored the activities antioxidant defense substances, such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH), toward their normal levels. These data were supplemented with histopathological examination of rat liver sections. The results demonstrated that baicalin could be proposed to protect the liver against CCl₄-induced oxidative damage in rats, and the possible underlying mechanism of the activity could be due to its free radical-scavenging and antioxidant activity.