Protective Effect of Cornuside against Carbon Tetrachloride-Induced Acute Hepatic Injury

This study elucidated the effects of cornuside on carbon tetrachloride (CCl₄)-induced hepatotoxicity. Rats were treated intraperitoneally with 0.5 mL/kg of CCl₄. Sixteen h after CCl₄ treatment, the levels of serum aminotransferases, tumor necrosis factor-α (TNF-α), and lipid peroxidation were significantly elevated, whereas the hepatic antioxidative enzyme activities were decreased. These changes were attenuated by cornuside. Histological studies also indicated that cornuside inhibited CCl₄-induced liver damage. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were elevated after CCl₄ treatment, while cytochrome P450 2E1 (CYP2E1) expression was suppressed. Cornuside treatment inhibited the formation of liver nitrite, and reduced the overexpression of iNOS and COX-2 proteins, but restored the liver CYP2E1 content as compared with the CCl₄-treated rats. Our data indicate that cornuside protects the liver from CCl₄-induced acute hepatotoxicity, perhaps due to its ability to restore the CYP2E1 function and suppress inflammatory responses, in combination with its capacity to reduce oxidative stress.     

Dose- and Time-Dependent Effects of Luteolin on Liver Metallothioneins and Metals in Carbon Tetrachloride-Induced Hepatotoxicity in Mice

The aim of this study was to investigate the protective effect of luteolin on liver Ca, Mg, Zn, Cu, Fe, and Mn content in mice with carbon tetrachloride (CCl4)-induced hepatotoxicity. Additionally, liver metallothionein (MT) expression was studied. Luteolin was administered intraperitoneally (i.p.) as a single 5- or 50-mg/kg dose or once daily for two consecutive days, respectively. Two hours after the last injection, the mice were treated with CCl4 (20 mg/kg, i.p.). CCl4 injection reduced hepatic level of all metals except Ca, with an intense cytoplasmic staining pattern in hepatocytes located in periportal areas, indicating induction of MTs. Pretreatment with 50 mg/kg of luteolin for 2 days remarkably elevated metal content to control values (Mg and Cu) or even above them (Zn and Fe). Luteolin pretreatment increased pericentral MTs immunopositivity and histological architecture improvement in a time- and dose-dependent manner, being the most prominent in mice pretreated with 50 mg/kg for 2 days. The liver in this group showed pronounced MT expression in almost all hepatocytes throughout the liver parenchyma. In conclusion, these results suggest the protective effect of luteolin on CCl4-induced hepatotoxicity and an enhancement of hepatocyte proliferative capabilities.     

海珠益肝胶囊对免疫性肝损伤模型小鼠的保护作用

目的：观察海珠益肝胶囊对卡介苗（BCG）加脂多糖（LPS）诱导的小鼠免疫性肝损伤的防护作用。方法：采用卡介苗（BCG）加脂多糖（LPS）诱导小鼠免疫性肝损伤,通过检测小鼠的血清谷丙转氨酶（ALT）和谷草转氨酶（AST）活性及肝脏病理变化来研究海珠益肝胶囊的保肝功能。结果：海珠益肝胶囊防治组小鼠血清ALT及AST活性比模型组显著降低,两组比较,差异有统计学意义。海珠益肝胶囊可明显减轻肝组织病理损伤,以大剂量组作用最佳;海珠益肝胶囊的使用使免疫性肝损伤小鼠肝细胞凋亡减少,且有剂量依赖关系。结论：海珠益肝胶囊对BCG加LPS诱导小鼠产生免疫性肝炎的模型免疫性肝损伤具有显著的保护作用。     

Prevention of Carbon Tetrachloride-Induced Lipid Peroxidation in Liver Microsomes from Dehydroepiandrosterone-Pretreated Rats

Dehydroepiandrosterone (DHEA), a lipid soluble steroid, administered to rats (100 mg/kg b.wt) by a single intraperitoneal injection, increases to twice its normal level in the liver microsomes. Microsomes so enriched become resistant to lipid peroxidation induced by incubation with carbon tetrachloride in the presence of a NADPH-regenerating system: also the lipid peroxidation-dependent inactivation of glucose-6-phosphatase and gamma-glutamyl transpetidase due to the haloalkane are prevented. Noteworthy, the liver microsomal drug-metabolizing enzymes and in particular the catalytic activity of cytochrome P₄₅₀IIE1, responsible for the CCl₄-activation, are not impaired by the supplementation with the steroid. Consistently, in DHEA-pretreated microsomes the protein covalent binding of the trichloromethyl radical (CCl₃°), is similar to that of not supplemented microsomes treated with CCl₄. It thus seems likely that DHEA protects liver microsomes from oxidative damage induced by carbon tetrachloride through its own antioxidant properties rather than inhibiting the metabolism of the toxin.     

Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea in Carbon Tetrachloride-Induced Liver Injury in Rat

Antrodia cinnamomea (A. cinnamomea) is an indigenous medical fungus in Taiwan and has multiple biological functions, including hepatoprotective and immune-modulatory effects. Currently, the commercially available A. cinnamomea are mainly liquid- and solid-state fermented A. cinnamomea. However, the hepatoprotective effect of solid-state fermented A. cinnamomea has never been reported. Here we evaluate the ability of air-dried, ground and non-extracted wheat-based solid-state fermented A. cinnamomea (WFAC) to protect against carbon tetrachloride (CCl₄)-induced hepatic injury in vivo. The results showed that oral administration of WFAC dose dependently (180, 540 and 1080 mg/kg) ameliorated the increase in plasma aspartate aminotransferase and alanine aminotransferase levels caused by chronic repeated CCl₄ intoxication in rats. WFAC significantly reduced the CCl₄-induced increase in hepatic lipid peroxidation levels and hydroxyproline contents, as well as reducing the spleen weight and water content of the liver. WFAC also restored the hepatic soluble protein synthesis and plasma albumin concentration in CCl₄-intoxicated rats, but it did not affect the activities of superoxide dismutase, catalase, or glutathione peroxidase. In addition, a hepatic morphological analysis showed that the hepatic fibrosis and necrosis induced by CCl₄ were significantly ameliorated by WFAC. Furthermore, the body weights of control rats and WFAC-administered rats were not significantly different, and no adverse effects were observed in WFAC-administered rats. These results indicate that WFAC is a nontoxic hepatoprotective agent against chronic CCl₄-induced hepatic injury.     

灰树花胞外多糖对四氯化碳致小鼠肝损伤的保护作用

四氯化碳可导致小鼠急性肝损伤,采用灰树花胞外多糖(GFP)防治后,对其血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)和过氧化氢酶活力(CAT)以及肝组织匀浆中的丙二醛(MDA)和乳酸脱氢酶(LDH)进行测定,与模型组相比较,灰树花胞外多糖治疗组ALT、AST、MDA、LDH活力明显降低,而CAT活力明显升高。通过组织切片染色可以直观的看出灰树花胞外多糖能显著减轻肝组织病理变化程度。结果显示GFP对CCL4致小鼠急性肝损伤具有保护作用。     

Prevention of Carbon Tetrachloride-Induced Lipid Peroxidation in Liver Microsomes from Dehydroepiandrosterone-Pretreated Rats

Dehydroepiandrosterone (DHEA), a lipid soluble steroid, administered to rats (100 mg/kg b.wt) by a single intraperitoneal injection, increases to twice its normal level in the liver microsomes. Microsomes so enriched become resistant to lipid peroxidation induced by incubation with carbon tetrachloride in the presence of a NADPH-regenerating system: also the lipid peroxidation-dependent inactivation of glucose-6-phosphatase and gamma-glutamyl transpetidase due to the haloalkane are prevented. Noteworthy, the liver microsomal drug-metabolizing enzymes and in particular the catalytic activity of cytochrome P₄₅₀IIE1, responsible for the CCl₄-activation, are not impaired by the supplementation with the steroid. Consistently, in DHEA-pretreated microsomes the protein covalent binding of the trichloromethyl radical (CCl₃°), is similar to that of not supplemented microsomes treated with CCl₄. It thus seems likely that DHEA protects liver microsomes from oxidative damage induced by carbon tetrachloride through its own antioxidant properties rather than inhibiting the metabolism of the toxin.     

香水莲花总提取物对小鼠急性酒精肝损伤的实验研究

目的:观察香水莲花提取物对酒精所致小鼠急性化学损伤的保护作用。方法:雄性昆明种小鼠70只,随机分为正常对照组、急性酒精肝损伤模型组、水飞蓟素阳性对照组(46.7 mg/kg)以及香水莲花低、中、高剂量组(120、180、240 mg/kg)共6组,检测肝组织甘油三酯(TG)、丙二醛(MDA)和还原型谷胱甘肽(GSH)含量,称量体重和肝脏重量。结果:香水莲花总提取物能够抑制急性酒精肝损伤小鼠肝组织的TG、MDA含量升高(P0.05),增加GSH含量(P0.05)。结论:香水莲花总提取物对急性酒精肝损伤有明显的保护作用。     

Comparison of the Preventive Activity of Isorhamnetin Glycosides from Atsumi-kabu (Red Turnip,Brassica, campestris L.) Leaves on Carbon Tetrachloride-Induced Liver Injury in Mice

Isorhamnetin 3-O-glucoside, which was contained together with isorhamnetin 3,7-di-O-glucoside in atsumi-kabu leaves, suppressed increases in the plasma ALT and AST activities of mice with liver injury induced by the injection of carbon tetrachloride, but no suppression by isorhamnetin 3,7-di-O-glucoside was apparent. This result indicates that the release of glucose at the 7-position in isorhamnetin 3,7-di-O-glucoside was very important to mitigating liver injury.     

藻蓝蛋白复合物对酒精性肝损伤的保护作用

本文对藻蓝蛋白复合物保护化学性肝损伤的功效学进行了研究.以Wistar大鼠建立酒精性肝损伤模型,将藻蓝蛋白复合物分为高、中、低三个剂量组,以联苯双酯作为阳性对照组,灌胃给药42 d,分别测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、血清丙二醛(MDA)、谷胱甘肽(CSH)、肝匀浆丙二醛(MDA)和谷胱甘肽(GSH)的含量,并对肝脏切片进行病理检查.结果表明:藻蓝蛋白复合物对血清ALT、AST具有显著的抑制作用,显著拮抗肝脏MDA的升高,显著提高肝脏GSH-Px含量.出现肝细胞浊肿、脂肪变性、点状坏死的大鼠数目极少.从而表明藻蓝蛋白复合物具有显著的保护酒精性肝损伤的功效.     

Antioxidant activity of extract from Polygonum cuspidatum

Numerous diseases are induced by free radicals via lipid peroxidation, protein peroxidation and DNA damage. It has been known that a variety of plant extracts have antioxidant activities to scavenge free radicals. Whether Polygonum cuspidatum Sieb. et Zuce has antioxidant activity is unknown. In this study, dried roots of Polygonum cuspidatum were extracted by ethanol and the extract was lyophilized. Free radical scavenging assays, superoxide radical scavenging assays, lipid peroxidation assays and hydroxyl radical-induced DNA strand scission assays were employed to study antioxidant activities. The results indicate that the IC50 value oí Polygonum cuspidatum extract is 110 microg/ml in free radical scavenging assays, 3.2 microg/ml in superoxide radical scavenging assays, and 8 microg/ml in lipid peroxidation assays, respectively. Furthermore, Polygonum cuspidatum extract has DNA protective effect in hydroxyl radical-induced DNA strand scission assays. The total phenolics and flavonoid content of extract is 641.1 +/- 42.6 mg/g and 62.3 +/- 6.0 mg/g. The results indicate that Polygonum cuspidatum extract clearly has antioxidant effects.     

Protective Effect of Metalloporphyrins against Cisplatin-Induced Kidney Injury in Mice

Oxidative and nitrative stress is a well-known phenomenon in cisplatin-induced nephrotoxicity. The purpose of this work is to study the role of two metalloporphyrins (FeTMPyP and MnTBAP), water soluble complexes, in cisplatin-induced renal damage and their ability to scavenge peroxynitrite. In cisplatin-induced nephropathy study in mice, renal nitrative stress was evident by the increase in protein nitration. Cisplatin-induced nephrotoxicity was also evident by the histological damage from the loss of the proximal tubular brush border, blebbing of apical membranes, tubular epithelial cell detachment from the basement membrane, or intra-luminal aggregation of cells and proteins and by the increase in blood urea nitrogen and serum creatinine. Cisplatin-induced apoptosis and cell death as shown by Caspase 3 assessments, TUNEL staining and DNA fragmentation Cisplatin-induced nitrative stress, apoptosis and nephrotoxicity were attenuated by both metalloporphyrins. Heme oxygenase (HO-1) also plays a critical role in metalloporphyrin-mediated protection of cisplatin-induced nephrotoxicity. It is evident that nitrative stress plays a critical role in cisplatin-induced nephrotoxicity in mice. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration and cisplatin-induced nephrotoxicity can be prevented with the use of metalloporphyrins.     

Protective Effect of Grape Seed Proanthocyanidins against Liver Ischemic Reperfusion Injury: Particularly in Diet-Induced Obese Mice

Background: Hepatic ischemia and reperfusion injury (IRI) is a major complication in liver surgery, and hepatic steatosis is a primary factor aggravating cellular injury during IRI. Both pro-inflammatory cytokines and reactive oxygen species (ROS) are key mediators of hepatic IRI. Ischemic preconditioning (IpreC), remote ischemia preconditioning (RIPC) and ischemic postconditioning (IpostC) have offered protections on hepatic IRI, but all these methods have their own shortcomings. Grape seed proanthocyanidins (GSP) has a broad spectrum of pharmacological properties against oxidative stress. Thus, GSP has potential protective effects against hepatic IRI.Methods: C57BL/6 mice suffering 30mins hepatic ischemia process were sacrificed after 1h reperfusion to build murine warm hepatic IRI model. The mice were injected GSP intraperitoneally 10, 20, 40mg/kg/day for 3 weeks as pharmacological preconditioning. Obese mice fed with high-fat diet for 24 weeks before used. Three pathways related to IRI, including ROS elimination, pro-inflammatory cytokines release and hypoxia responses were examined.Results: Our data show that GSP could significantly reduce hepatic IRI by protecting hepatocyte function and increasing the activity of ROS scavengers, as well as decreasing cytokines levels. At the same time, GSP also enhance the hypoxia tolerance response. Combined GSP and postconditioning can provided synergistic protection. In the obese mice suffering hepatic IRI group, GSP was more effective than postconditioning on protecting liver against IRI, and the combined strategy was obviously superior to the solo treatment.Conclusion: GSP could protect liver against IRI: particularly in high-fat diet induced obese mice. GSP used as pharmacological preconditioning and combined with other protocols have huge potential to be used in clinical.     

Protective Effects of the Flavonoid-Rich Fraction from Rhizomes of Smilax glabra Roxb. on Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Hepatoprotective agents could prevent tissue damage and reduce morbidity and mortality rates; such agents may include folkloric or alternative treatments. The present study evaluated the protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. (SGF) on carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Sprague-Dawley male rats were orally treated with SGF daily and received CCl₄ intraperitoneally twice a week for 4 weeks. Our results showed that SGF at doses of 100, 300 and 500 mg/kg significantly reduced the elevated activities of serum aminotransferases (ALT and AST), alkaline phosphatase and lactate dehydrogenase and the level of hepatic thiobarbituric acid–reactive substances compared to the CCl₄-treated group. Moreover, SGF treatment was also found to significantly increase the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glutathione compared with CCl₄-induced intoxicated liver. Histopathologic examination revealed that CCl₄-induced hepatic damage was markedly reversed by SGF. The results suggest that SGF has hepatoprotective and antioxidant properties in CCl₄-induced liver injury in rats.     

虎杖提取物对弹性蛋白酶的抑制作用研究

本文主要研究了虎杖提取物对弹性蛋白酶的抑制作用。实验利用热水浸渍法提取虎杖得到粗提取物1(CE1),聚酰胺柱层析后得到粗提取物2(CE2),并进行一系列的定性及定量分析。分别用紫外分光光度法和荧光光谱法研究了提取物对弹性蛋白酶的抑制作用和荧光猝灭作用。实验结果表明CE1和CE2中均含有虎杖苷,含量分别为41.01%和69.57%。CE1、CE2和虎杖苷对弹性蛋白酶有一定的抑制作用,当浓度为2.0 mg/mL时,它们对弹性蛋白酶的抑制率分别为53.56%、61.27%和82.53%。CE1、CE2和虎杖苷对弹性蛋白酶均有明显的内源荧光猝灭作用,当浓度为0.1 mg/mL时,荧光猝灭率分别为70.38%、72.90%和75.99%。     

The Protective Effect of Esculentoside A on Experimental Acute Liver Injury in Mice

Inflammatory response and oxidative stress are considered to play an important role in the development of acute liver injury induced by carbon tetrachloride (CCl₄) and galactosamine (GalN)/lipopolysaccharides (LPS). Esculentoside A (EsA), isolated from the Chinese herb phytolacca esculenta, has the effect of modulating immune response, cell proliferation and apoptosis as well as anti-inflammatory effects. The present study is to evaluate the protective effect of EsA on CCl₄ and GalN/LPS-induced acute liver injury. In vitro, CCK-8 assays showed that EsA had no cytotoxicity, while it significantly reduced levels of TNF-α and cell death rate challenged by CCl₄. Moreover, EsA treatment up-regulated PPAR-γ expression of LO2 cells and reduced levels of reactive oxygen species (ROS) challenged by CCl₄. In vivo, EsA prevented mice from CCl₄-induced liver histopathological damage. In addition, levels of AST and ALT were significantly decreased by EsA treatment. Furthermore, the mice treated with EsA had a lower level of TNF-α, Interleukin (IL)-1β and IL-6 in mRNA expression. EsA prevented MDA release and increased GSH-Px activity in liver tissues. Immunohistochemical staining showed that over-expression of F4/80 and CD11b were markedly inhibited by EsA. The western bolt results showed that EsA significantly inhibited CCl₄-induced phosphonated IkBalpha (P-IκB) and ERK. Furthermore, EsA treatment also alleviated GalN/LPS-induced acute liver injury on liver enzyme and histopathological damage. Unfortunately, our results exhibited that EsA had no effects on CCl₄-induced hepatocyte apoptosis which were showed by TUNEL staining and Bax, Caspase-3 and cleaved Caspase-3 expression. Our results proved that EsA treatment attenuated CCl₄ and GalN/LPS-induced acute liver injury in mice and its protective effects might be involved in inhibiting inflammatory response and oxidative stress, but not apoptosis with its underlying mechanism associated with PPAR-γ, NF-κB and ERK signal pathways.     

杭白菊保肝作用研究

本实验对杭白菊的保肝作用进行了研究。以四氯化碳诱导的小鼠急性肝损伤为模型,将杭白菊乙醇提取物和多糖部分分为高、中、低三个剂量组,以联苯双酯为阳性对照,灌胃给药8 d,分别测定血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、肝匀浆丙二醛(MDA)、肝匀浆超氧化物歧化酶(SOD)。结果表明:杭白菊乙醇提取物和多糖部分高剂量组对血清GPT、GOT具有显著的抑制作用,杭白菊乙醇提取物高剂量组显著拮抗肝脏MDA的升高。表明杭白菊有保护四氯化碳所致肝损伤的作用。     

Lipid-lowering effects of polydatin from Polygonum cuspidatum in hyperlipidemic hamsters

Hyperlipidaemias are common in obese people, and they increase the risk of cardiovascular diseases such as coronary heart disease (CHD) and atherosclerosis (AS). Previous studies have shown that several drugs can depress serum cholesterol. However, they could cause serious side effects in various clinical settings. The objective of the present study was to evaluate the lipid-lowering effects of polydatin in high-fat/cholesterol (HFC)-fed hamsters. The levels of lipids in hamsters were measured enzymatically before and after the administration of polydatin. Significant differences between HFC and HFC+polydatin were detected for those concentrations. Decreased levels of serum TC, TG and LDL-C and the concentrations of hepatic TG were found. Experimental results also showed that polydatin elevated LDL-C/HDL-C and TC/HDL-C ratios. In concert with other effects, serum cholesterol-lowering effect in hamsters may contribute to the regulation properties attributed to polydatin.     

Enhancement of fluoride activity against Streptococcus mutans biofilms by a substance separated from Polygonum cuspidatum

Polygonum cuspidatum is a plant with spreading rhizomes and numerous reddish-brown stems that has been used in Korean folk medicine to improve oral hygiene. Nevertheless, there are no reports related to its possible effect on the virulence of dental biofilms. In this study, the ability of a fraction (F1) separated from P. cuspidatum, alone or in combination with fluoride, to disrupt virulence factors and the composition of Streptococcus mutans biofilms was examined. F1 was mainly composed of resveratrol, emodin and physcion (approximately 16.2%, 18.9% and 2.07% of the weight of F1, respectively). F1 showed inhibitory effects on acid production and F-ATPase activity of S. mutans in biofilms, and could enhance fluoride activity against acid production and acid tolerance of S. mutans in biofilms. When S. mutans biofilms were briefly treated with F1 (10 min, a total of five times), the biomass accumulation, water-insoluble polysaccharides and intracellular iodophilic polysaccharides were reduced. Furthermore, the fluoride activity against biomass accumulation was enhanced by F1. These results suggest that F1 may be useful in the control of dental biofilms and in improving the cariostatic properties of fluoride without increasing its exposure.