重用赤芍治疗ANIT诱导大鼠急性淤胆型肝炎的研究

目的:观察不同剂量赤芍对α-萘异硫氰酸酯(α-naphthylisothiocy,ANIT)诱导大鼠急性淤胆型肝炎的保护作用.方法:赤芍高、中、低(分别相当于原生药量36,18,1g·kg-1)剂量ig给药3 d(2次/d)后,采用ANIT(60 mg·kg-1)诱导大鼠急性淤胆型肝炎模型,造模后继续给药3次,末次给药1h后,进行胆管引流,记录大鼠6h内的胆汁流量,检测血清学指标变化及肝脏病理学改变,结合对应分析综合评价赤芍对ANIT诱导大鼠急性淤胆型肝炎的影响.结果:血清生化结果显示,与模型组相比,赤芍中、高剂量给药组血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、碱性磷酸酶(ALP)、总胆汁酸( TBA)明显降低(P＜0.01),胆汁流量显著升高(P＜0.05),低剂量组变化不明显;病理组织学观察结果显示,与模型组相比,赤芍中、高剂量组肝脏病变均有明显改善,低剂量组改善不明显;对应分析结果表明,赤芍中、高剂量组的治疗效果显著,且呈剂量依赖性增强.结论:高、中剂量赤芍(36,18 g·kg-1)对ANIT诱导的大鼠急性淤胆型肝炎有显著的保护作用.     

Preclinical evidence of Yinchenhao decoction on cholestasis: A systematic review and meta‐analysis of animal studies

Cholestasis is an important cause of liver fibrosis and cirrhosis. Yinchenhao decoction has been used as a well‐known traditional Chinese medicine used in the treatment of cholestasis for over 2,000 years. The purpose of this systematic review is to evaluate the preclinical evidence of Yinchenhao decoction on cholestasis models. The following databases were searched from inception to February 2020. Chinese National Knowledge Infrastructure, VIP medicine information system, Wanfang Database, PubMed, Web of Science, Embase and the Cochrane Library were searched. The content concerned Yinchenhao decoction on different animal model experiments for the treatment of cholestasis. The methodological quality of the included studies was assessed based on the SYstematic Review Center for Laboratory animal Experimentation Animal Experiment Bias Risk Assessment Tool. A meta‐analysis was conducted with RevMan 5.3 software according to the Cochrane tool. Nineteen studies on a total of 404 animals were included with five kinds of experimental animal models. The results showed that serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin and total bile acid in the group treated with Yinchenhao decoction were significantly lower than those in the model group (P < 0.00001). The alanine aminotransferase (ALT), aspartate aminotransferase and alkaline phosphatase levels in the Yinchenhao decoction group were also significantly reduced (P < 0.00001). The subgroup analysis of the different models showed that Yinchenhao decoction had a significant effect on the bile duct ligation model, and there was a significant reduction in TBIL, DBIL and ALT levels (P < 0.00001) in ANIT‐induced cholestasis. After 24 hours of Yinchenhao decoction treatment, there was no significant difference in TBIL levels (P = 0.34), but after 48 and 72 hours of treatment, the TBIL levels were significantly reduced compared with the model group (P < 0.00001). There was no significant difference in DBIL after 48 hours of administration (P = 0.26), but compared with the model group, Yinchenhao decoction could significantly reduce the DBIL levels after 48 hours of treatment (P < 0.0003). Yinchenhao decoction could significantly reduce the ALT levels after 24, 48 and 72 hours (P < 0.006). Yinchenhao decoction was able to significantly reduce the levels of TBIL, DBIL and ALT on different rat species: Wistar and Sprague Dawley (P = 0.0001; P = 0.0002). The preclinical evidence indicated that Yinchenhao decoction might be a potent and promising agent for cholestasis. Moreover, this conclusion should be further confirmed with more well‐designed researches.     

Palbinone from Paeonia suffruticosa Protects Hepatic Cells via Up‐regulation of Heme Oxygenase‐1

Paeonia suffruticosa has been traditionally employed for vitalizing blood circulation and alleviating liver and inflammatory diseases. The pathways by which palbinone (PB) isolated from P. suffruticosa mediates heme oxygenase‐1 (HO‐1) induction were investigated using the specific inhibitors for PI3K and mitogen activated protein kinases pathways. The effect of PB‐treatment on Nrf2 translocalization and HO‐1‐antioxidant response element (ARE) regulation was examined employing Western blot and luciferase assays. PB induced HO‐1 expression via the activation of Nrf2 in the hepatic cells, and ARE‐dependent genes were stimulated via the PB‐mediated Nrf2 activation. PB‐mediated HO‐1 expression could be involved with PI3K/Akt and ERK1/2 pathways. Our study suggests the mechanism by which PB induces HO‐1 expression in the hepatic cells. This might substantiate the traditional applications of P. suffruticosa for the treatment of oxidative stress‐related diseases including oxidant and inflammatory‐mediated vascular and liver diseases. Copyright © 2013 John Wiley & Sons, Ltd.     

基于转运体的何首乌致肝损伤作用机制探讨

目的：阐明长期给药何首乌醇提物 (PME) 和水提物 (PMW) 致大鼠肝损伤的可能机制。方法：分别制备 PME 和 PMW。雄性 SD 大鼠随机分为对照组、阳性对照异硫氰酸 α-萘酯 (ANIT 100 mg·kg^–1) 组、PMW组 (15 g·kg^–1)、PME 组 (12 g·kg^–1)。PME、PMW 组大鼠给药剂量相当于 60 g·kg^–1生药量,约为临床最大量的110 倍,灌胃给药 42 d,每日给药 1 次。ANIT 组于第 40 天灌胃给药 1 次。采用试剂盒方法检测大鼠血清生化指标丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、总胆汁酸 (TBA)、碱性磷酸酶 (ALP)、总胆红素(TBIL) 水平;采用苏木素-伊红 (HE) 染色法检测大鼠肝脏病理变化;采用实时荧光定量聚合酶链式反应 (qRT-PCR) 测 定 给 药 后 大 鼠 肝 脏 组 织 中 胆 汁 酸 、 胆 红 素 代 谢 相 关 转 运 体 有 机 阴 离 子 转 运 多 肽 1a1 (OATP1a...     

加味茵陈蒿汤对大鼠胆汁淤积性肝病的治疗作用

目的:探讨加味茵陈蒿汤对α-异硫氰酸萘酯(ANIT)诱导胆汁淤积性肝病(CSLD)大鼠模型的治疗作用。方法:将56只大鼠随机分为7组,分别为空白组,模型组,复方甘草酸苷胶囊组(22.5,45 mg·kg^-1),加味茵陈蒿汤低、中、高剂量组(4.1,8.1,16.2 g·kg^-1)。以ANIT(100 mg·kg^-1)灌胃1次,制备胆汁淤积性肝损伤模型。复方甘草酸苷胶囊及加味茵陈蒿汤在造模第2天开始灌胃给药,连续4 d。第5天进行胆管插管手术测量大鼠胆汁流速,取血清检测各组总胆红素(TBIL),直接胆红素(DBIL),间接胆红素(IBIL),丙氨酸氨基转移酶(ALT)和总胆汁酸(TBA)等血清学指标。采用苏木素-伊红(HE)染色观察肝组织病理变化。采用蛋白免疫印迹法(Western blot)检测大鼠肝组织中G蛋白偶联胆汁酸受体(TGR5),核苷酸结合寡聚化结构域样受体3(NLRP3),半胱氨酸蛋白酶-1(Caspase-1)蛋白表达情况。结果:与空白组比较,模型组胆汁流速显著降低(P<0.01),各血清学指标均显著增高(P<0.01),肝组织病变严重,且肝组织中TGR5,Caspase-1蛋白表达显著增强(P<0.01);与模型组比较,复方甘草酸苷胶囊组对于胆汁流速和血清学指标无显著影响,加味茵陈蒿汤高剂量组胆汁流速增快(P<0.05),各血清学指标均降低(P<0.05),复方甘草酸苷胶囊组和加味茵陈蒿汤组大鼠肝组织病变均有不同程度地改善,且肝组织中TGR5,Caspase-1蛋白表达均明显降低(P<0.05)。结论:加味茵陈蒿汤可有效治疗大鼠CSLD,其机制可能与胆汁酸分子及胆汁酸受体TGR5介导的炎症因子有关。     

Antidiabetic and antioxidant effects of oleanolic acid from Ligustrum lucidum Ait in alloxan‐induced diabetic rats

The present study evaluated the antidiabetic and antioxidant effects of oleanolic acid (OA) from Ligustrum lucidum Ait (LLA) in alloxan‐induced diabetic rats. OA in the alloxan‐induced diabetic rats showed significant hypoglycemic activity by lowering blood glucose (at doses of 60 and 100 mg/kg for 40 days). The levels of serum total cholesterol (TC), triglycerides (TG) and low‐density lipoprotein cholesterol (LDL‐c) in the OA‐treated diabetic rats were lower, and the high‐density lipoprotein cholesterol (HDL‐c) level was higher than in the control diabetic rats. A significant reduction in the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels of diabetic rats following OA treatment was also observed. Furthermore, OA treatment decreased the malondialdehyde (MDA) level, but increased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐px) activities of the liver and kidney in diabetic rats. These results indicate that OA could protect the liver function avoiding alloxan‐induced damage; OA had hypoglycemic, hypolipidemic and antioxidant efficacy in the diabetic rats. The antioxidant ability of OA might be one of the mechanisms of its hypoglycemic and hypolipidemic effects. Copyright © 2009 John Wiley & Sons, Ltd.     

小柴胡颗粒激活Nrf2通路抗TAA致大鼠急性肝损伤的机制探讨

目的:观察小柴胡颗粒对硫代乙酰胺(TAA)致大鼠急性肝损伤(ALI)的治疗作用,探讨核转录因子(NF)-E2相关因子2(Nrf2)抗氧化损伤通路在其中的作用。方法:SD大鼠随机分为空白组,模型组,小柴胡颗粒低、中、高剂量组(1,2,4 g·kg-1),大鼠给予250 mg·kg-1TAA腹腔注射2 d制备肝损伤模型,从第3天各组分别给予等量双蒸水和不同剂量小柴胡颗粒,灌胃2周。末次给药后24 h取材,肝组织行苏木素-伊红(HE)染色;比色法测定血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)活性及组织中总超氧化物歧化酶(T-SOD),丙二醛(MDA)水平;实时荧光定量PCR(Real-time PCR)检测Nrf2通路相关mRNA表达;蛋白免疫印迹法(Western blot)检测Nrf2通路相关蛋白的表达。结果:与空白组比较,模型组ALT,AST,MDA水平显著增高,T-SOD活性明显降低(P 0. 05,P 0. 01),病理学呈现大片炎性浸润表现,肝脏组织Nrf2,Kelch样环氧氯丙烷相关蛋白1(Keap1),醌氧化还原酶1(NQO1),血红素加氧酶-1(HO-1),谷氨酸半胱氨酸合成酶催化亚基(GCLC),谷氨酸半胱氨酸合成酶调节亚基(GCLM) mRNA及蛋白表达水平均明显下降(P 0. 05,P 0. 01);与模型组比较,小柴胡颗粒各剂量组ALT,AST,MDA水平均明显降低,T-SOD活性明显升高(P 0. 05,P 0. 01),病理结果示大鼠肝脏病变范围与严重程度均有不同程度改善,肝脏组织Nrf2,Keap1,NQO1,HO-1,GCLC,GCLM的mRNA及蛋白表达水平均明显升高(P 0. 05,P 0. 01)。结论:小柴胡颗粒可能通过上调Nrf2信号通路上下游分子的表达,对TAA致急性肝损伤大鼠起到治疗作用。     

Oridonin induces ferroptosis by inhibiting gamma‐glutamyl cycle in TE1 cells

Oridonin (Ori) is a natural tetracyclic diterpenoid active compound with excellent antitumor activity, but the mechanism of Ori on esophageal cancer cell, TE1, remains unclear. In this study, we examined the levels of intracellular iron, malondialdehyde, and reactive oxygen species after Ori treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1 cell proliferation is associated with ferroptosis. To understand the molecular mechanism of Ori, we performed UPLC–MS/MS metabolomics profiling on TE1 cells, which show that gamma‐glutamyl amino acids (gamma‐glutamylleucine, gamma‐glutamylvaline), 5‐oxoproline, glutamate, GSH, and GSSG are changed significantly after Ori treatment. Meanwhile, the activity of gamma‐glutamyl transpeptidase 1 (GGT1) decreased. This revealed that Ori inhibited the gamma‐glutamyl cycle in TE1 cells. Furthermore, we found that Ori can covalently bind to cysteine to form the conjugate oridonin‐cysteine (Ori‐Cys), resulting in the inhibition of glutathione synthesis, which is consistent with the decrease in the enzymatic activity of glutamate cysteine ligase catalytic subunit (GCLC). Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased. In conclusion, our experiments indicated that Ori can inhibit the gamma‐glutamyl cycle, thereby inducing ferroptosis to exert anti‐cancer activity.     

Neuroprotective Effects of Puerarin on 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine induced Parkinson's Disease Model in Mice

Puerarin, an active component of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep is well‐known for its anti‐oxidative and neuroprotective activities. Although anti‐Parkinson's disease activity of puerarin was reported in both of in vivo and in vitro model, detailed mechanisms are not clarified. In this study, we addressed that puerarin attenuated 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced behavioral deficits, dopaminergic neuronal degeneration and dopamine depletion. Puerarin administration enhanced glutathione (GSH) activity, glial cell line‐derived neurotrophic factor (GDNF) expression and PI3K/Akt pathway activation, which might ameliorate MPTP injection‐induced progressive elevation of reactive oxygen species (ROS) formation in mice. In addition to the effect on ROS, puerarin ameliorated MPTP‐reduced lysosome‐associated membrane protein type 2A (Lamp 2A) expression. Taken together, our data demonstrate that puerarin attenuates MPTP‐induced dopaminergic neuronal degeneration via modulating GDNF expression, PI3K/Akt pathway and GSH activation, which subsequently ameliorate MPTP‐induced ROS formation and decrease of Lamp 2A expression. Copyright © 2013 John Wiley & Sons, Ltd.     

Serum Metabolomic Profiling in a Rat Model Reveals Protective Function of Paeoniflorin Against ANIT Induced Cholestasis

Cholestasis is a leading cause of hepatic accumulation of bile acids resulting in liver injury, fibrosis, and liver failure. Paeoniflorin displays bright prospects in liver protective effect. However, its molecular mechanism has not been well‐explored. This study was designed to assess the effects and possible mechanisms of paeoniflorin against alpha‐naphthylisothiocyanate‐induced liver injury. Ultraperformance liquid chromatography coupled with quadrupole time‐of‐flight combined with principle component analysis and partial least squares discriminant analysis were integrated to obtain differentiating metabolites for the pathways and clarify mechanisms of disease. The results indicated that paeoniflorin could remarkably downregulate serum biochemical indexes and alleviate the histological damage of liver tissue. Different expression of 14 metabolites demonstrated that paeoniflorin mainly regulated the dysfunctions of glycerophospholipid metabolism and primary bile acid biosynthesis. Moreover, several pathways such as arginine and proline metabolism, ether lipid metabolism, and arachidonic acid metabolism were also related to the efficacy. In conclusion, paeoniflorin has indicated favorable pharmacological effect on serum biochemical indexes and pathological observation on cholestatic model. And metabolomics is a promising approach to unraveling hepatoprotective effects by partially regulating the perturbed pathways, which provide insights into mechanisms of cholestasis. Copyright © 2016 John Wiley & Sons, Ltd.     

阴黄证动物模型的建立及其意义

目的 :探讨阴黄证动物模型的制作方法。方法 :利用 40 0 %的大黄煎剂 ,按 50 ml/kg/只的剂量 ,灌胃 1 5d,2 % α-荼异氰酸 (ANIT) 6ml/kg/只灌胃 1次 ,制作阴黄证动物模型 ,并用茵陈术附汤做治疗反证。观察大鼠症状、体征 ,检测血清白介素 2受体 (SIL- 2 R) ,肝功能如谷丙转氨酶 (ALT)、谷草转氨酶 (AST)、胆汁酸 (TBA)等以及 D-木糖吸收率等指标。结果 :阴黄证大鼠出现明显阳虚表现 ,体重下降显著 ,高胆红素、SIL-2 R升高 ,经茵陈术附汤治疗后 ,症状及指标均有好转。结论 :ANIT联合大黄制作阴黄证动物模型是成功的 ,并存在着持续高胆红素血症和免疫功能低下特点     

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??OBJECTIVE To investigate the preventive protective effect of matrine(MT) on ??-naphthl isocyanate(ANIT)-induced cholestasis in rat, and to explore its possible mechanism. METHODS Thirty SD rats were randomly divided into five groups with six rats in each group: normal control group, model group, low dose matrine(5 mgkg^-1), high dose matrine group(10 mgkg^-1) and positive control group(ursodeoxycholic acid 100 mgkg^-1), which were administered continuously for 7 d. All groups except the normal control group were given 60 mgkg^-1 ANIT at the fifth day. After the last administration, all rats were fasted 24 h and arterial blood were collected to detect the indexes of total bilirubin(TBIL), aspartate aminotransferase(AST), alanine aminotransferase(ALT) and alkaline phosphatase(ALP). The livers were picked for HE staining, immunohistochemistry(IHC) analysis and Western blot(WB), to indentify the protein expressions of CYP3A4 and PXR. RESULTS Compared to model group, low-dose and high-dose matrine decreased TBIL, AST, ALT and ALP significantly; IHC analysis showed that the expression of CYP3A4 in high-dose group was significantly higher than that in model group(P??0.05). The results of WB showed that the expressions of CYP3A4 and PXR in two matrine groups were significantly higher than that in model group(P??0.05), however, only CYP3A4 expression in UDCA group was significantly higher than that in model group(P??0.05). CONCLUSION Matrine could improve cholestatic liver injury in rats and its mechanism might be related to the upregulation of CYP3A4 expression controled by inducing PXR expression.     

Paeonol extracted from Paeonia suffruticosa Andr. ameliorated UVB‐induced skin photoaging via DLD/Nrf2/ARE and MAPK/AP‐1 pathway

Paeonia suffruticosa Andr. (PS) has been used in traditional Chinese medicine for a long time. However, there are no studies that investigate the preventive effects of PS on ultraviolet B (UVB)‐induced photoaging. In this study, paeonol (PA) was detected the main compound in PS root. In vitro, PS and PA significantly inhibited UVB‐induced phosphorylation of mitogen‐activated protein kinase and activator protein 1 in keratinocytes, which consequently led to degradation of procollagen type I. On the other hand, PS and PA increased NAD(P)H:quinone oxidoreductase 1 and heme oxygenase‐1 expression, confirmed by greater nuclear accumulation of nuclear factor E2‐releated factor 2 (Nrf2). Furthermore, this study proved that the endogenous antioxidant system Nrf2/antioxidant response element was regulated by dihydrolipoamide dehydrogenase, a tricarboxylic acid (TCA) cycle‐associated protein whose level was decreased after UVB exposure. PS and PA promoted the production of dihydrolipoamide dehydrogenase, as well as the activation of Nrf2 and antioxidant response element, resulting in preventing procollagen type I ruined caused by UVB. In vivo, topical application of PS and PA attenuated UVB‐induced matrix metalloproteinase‐1 production and promoted procollagen type I in hairless mice. These results suggested PA a promising botanical in protecting skin from UVB‐induced photoaging.     

Hepatoprotective effect of Hypericum japonicum extract and its fractions

OBJECTIVE: To investigate the hepatoprotective activity of different parts of Hypericum japonicum against carbon tetrachloride(CCl(4))-induced hepatitis and alpha-naphthyl-isothiocyanate (ANIT)-induced cholestasis. MATERIALS AND METHODS: Mice were divided into groups and then administrated orally with solutions extracted from herbs before they were modeled in the experiments. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (T-BIL) in serum were evaluated. HPLC fingerprint was used for phytochemical analysis of the extracts. RESULTS: The total aqueous extract of Hypericum japonicum had an obvious effect on the decreasing of AST, ALT and T-BIL levels in serum. The isolated fraction IV (F4) exhibited a preferable activity of ameliorating cholestasis, while Fraction V (F5) was more efficacious in protecting liver from injury. Chemical fingerprint indicated that F5 contained several flavonoids which might be the active chemicals against hepatotoxicity. CONCLUSION: Different fractions of Hypericum japonicum manifest different effect, indicating their different potentials as candidacies of new drugs.     

Efficacy of a Standardized Extract of Prunus mume in Liver Protection and Redox Homeostasis: A Randomized,Double‐Blind,Placebo‐Controlled Study

The antioxidant, anti‐inflammatory and hepatoprotective effects of Prunus mume (PM) have previously been demonstrated. This double‐blind, placebo‐controlled study was designed to evaluate the influence of two doses of a food supplement, made of 150 mg of a standardized PM extract on liver transaminases, lipid profile, glycemia, neopterin and reduced and oxidized thiols in plasma and erythrocytes, during a 3‐month treatment period, in healthy subjects with transaminases levels between 20 and 40 UI/L. Forty‐five subjects (56.0 ± 11.6 years) were enrolled. The results showed a beneficial and statistically significant effect versus placebo of PM extract on liver function, with a decrease versus baseline in alanine aminotransferase (47%), aspartate aminotransferase (7%), gamma‐glutamyl transpeptidase (15%) and glycemia (11%). The lipid profile modification was also positive with an increase versus baseline in HDL cholesterol (13%), and a decrease in LDL/HDL ratio (12%) and triglycerides (8%). The antioxidant action of PM translated into a decrease in oxidized glutathione, reduced/oxidized cysteine‐glycine, oxidized cysteine (intracellular pro‐oxidant) and neopterin (inflammation biomarker), was associated with an increase in reduced glutathione. These results are in favor of the use of a standardized extract of P. mume for the support of liver health and prevention of common metabolic and inflammation‐based diseases. Copyright © 2016 John Wiley & Sons, Ltd.     

Efficacy of artichoke leaf extract in non‐alcoholic fatty liver disease: A pilot double‐blind randomized controlled trial

Non‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and is potentially treatable, though there are few therapeutic agents available. Artichoke leaf extract (ALE) has shown potential as a hepatoprotective agent. This study sought to determine if ALE had therapeutic utility in patients with established NAFLD. In this randomized double‐blind placebo‐controlled parallel‐group trial, 100 subjects with ultrasound‐diagnosed NAFLD were randomized to either ALE 600 mg daily or placebo for a 2‐month period. NAFLD response was assessed by liver ultrasound and serological markers including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and AST to platelet ratio index (APRI) score. Ninety patients completed the study (49 ALE and 41 placebo) with no side effects reported. ALE treatment compared with placebo: Doppler sonography showed increased hepatic vein flow (p < .001), reduced portal vein diameter (p < .001) and liver size (p < .001), reduction in serum ALT (p < .001) and AST (p < .001) levels, improvement in AST/ALT ratio and APRI scores (p < .01), and reduction in total bilirubin. ALE supplementation reduced total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, non‐high‐density lipoprotein cholesterol, and triglyceride concentrations (p = .01). This study has shown beneficial effects of ALE supplementation on both ultrasound liver parameters and liver serum parameters (ALT, AST, APRI ratio, and total bilirubin) in patients with NAFLD.     

茯苓多糖退黄疸作用的实验研究

目的: 以异硫氰酸-α-萘酯(alpha-naphthylisothi,ANIT)大鼠黄疸模型为载体,探索茯苓多糖退黄作用。 方法: Wistar雄性大鼠50只随机分为正常组(10只)和ANIT处理组(40只),2%的ANIT按照6 mL·kg^-1 ig,48 h后ANIT处理组大鼠随机分为模型对照组及茯苓多糖低、中、高剂量(5,50,500 mg·kg^-1),每组10只。模型大鼠每天ig给予生理盐水。茯苓多糖组ig给药1周,实验结束处死全部大鼠,检测大鼠肝功能及实时定量(real-time PCR)方法检测白介素-1β(IL-1β)及肿瘤坏死因子(TNF-α)水平。 结果: ANIT处理组大鼠肝功能紊乱,与正常组相比,血清总胆红素(TBil)含量显著升高(P<0.01),为正常组的52.7倍,谷丙转氨酶(ALT)活性显著升高(P<0.01),为正常组的6.31倍,天冬氨酸转氨酶(AST) 活性显著升高(P<0.01),为正常组的8.31倍。茯苓多糖退黄疸保肝作用呈剂量依赖型增高,中剂量组退黄有一定作用,高剂量组退黄作用最为显著。ANIT造模组IL-1β, TNF-α mRNA促炎症因子显著升高(P<0.01),分别为正常组的14.24,10.65倍;而模型组IL-4 mRNA表达仅为正常组的0.33(P<0.01);与模型组相比,高剂量茯苓多糖显著抑制IL-1β,TNF-α的mRNA表达(P<0.01),茯苓多糖高剂量组显著提高IL-4 mRNA表达(P<0.01)。 结论: 高剂量茯苓多糖可能通过免疫调节发挥退黄作用。     

Persicarin from water dropwort (Oenanthe javanica) protects primary cultured rat cortical cells from glutamate‐induced neurotoxicity

The n‐BuOH fraction of O. javanica significantly protected the primary cultures of rat cortical cells exposed to glutamate. Four flavonoids yielded from this fraction through bioactivity‐guidance. The isolated compounds, identified as isorhamnetin (1), afzelin (2), hyperoside (3) and persicarin (4), were evaluated in vitro for their neuroprotective activity. Persicarin (4), the main constituent of O. javanica, showed significant neuroprotective activities in glutamate‐injured rat cortical cells. Persicarin diminished calcium influx and inhibited the subsequent overproduction of nitric oxide and intracellular peroxide. In addition, persicarin significantly restored the reduced activities of glutathione (GSH) reductase and glutathione peroxidase, and the contents of GSH induced by glutamate. These results support a conclusion that persicarin greatly contributes to the neuroprotective activities of O. javanica. Copyright © 2009 John Wiley & Sons, Ltd.