五味子的研究新进展

五味子(Schisanda ChinensisBaill.)属木兰科植物,又名山花椒,其药用部位是果实,性温,入肺、肾二经,具有滋肾敛肺、生津收汗、涩精、安神之功能。笔者主要就五味子近几年在化学成分、药理活性以及栽培和种植方面的研究进行了汇总与分析,以期对五味子的开发和利用有参考作用。1化学成分1.1五味子乙素五味子乙素具有显著降酶、抗脂质过氧化作用。文献报道,提取五味子乙素的最佳条件为加5倍量85%的乙醇、调pH值为5.5、回流提取2h〔1〕。1.2五味子多糖多糖具有调节免疫功能、抗肿瘤、抗病毒病菌、降血糖血脂、抗溃疡等作用。研究表明,温度和料…     

五味子乙素对H22荷瘤小鼠抑制作用的病理学研究

目的:研究五味子乙素、顺铂和两者联合应用对H22荷瘤鼠的抑瘤作用。方法:建立小鼠H22实体瘤模型,对H22小鼠进行五味子乙素、顺铂和两者联合处理,瘤体经HE染色,镜下观察瘤体体积和病理学变化。结果:五味子乙素可在一定程度上使瘤细胞退变、凋亡,有较轻抑瘤形态学表现。五味子乙素合并顺铂有较强抑瘤作用。结论:五味子乙素具有一定的抑瘤作用,其抑瘤作用可能与细胞凋亡、活化免疫细胞有关。且五味子乙素与顺铂合用可使抑瘤作用增强。     

五味子乙素的药理作用及其分子机制的研究进展

五味子是木兰科植物五味子的干燥成熟果实,是著名的滋补性中药,习称“北五味子”。其单体活性成分五味子乙素具有保肝、抗炎、抗肿瘤及抗氧化等多种药理作用,临床广泛应用于肝病的防护与治疗、心脑血管疾病、多种神经退行病变等领域。现对五味子乙素的药理作用、安全性及生物利用度等相关国内外最新研究现状作一系统综述,为进一步研究、开发和合理应用五味子乙素提供参考。     

五味子抗肿瘤活性成分及作用机制研究进展

五味子是一味常用的中药材。近年来,国内外对其抗肿瘤活性成分及作用机制研究日趋活跃。目前认为五味子主要抗肿瘤成分为多糖和木脂素。五味子抗肿瘤机制有多个方面,包括诱导肿瘤细胞凋亡、提高机体的免疫调节作用、抗氧化、清除自由基作用、抗突变和逆转肿瘤细胞的多药耐药性。该文对五味子抗肿瘤活性成分和作用机制进行综述,以促进五味子研究的开展及临床上更好的应用。     

五味子乙素抗大鼠肝癌作用机制研究

目的研究五味子乙素对大鼠肝癌的影响,并阐明其机制。方法将50只大鼠随机分为五组,采用移植法建模,C、E、D组分别给予相同剂量的环磷酰胺、五味子乙素以及二者混合物,测定各组瘤重以及TNF-d水平。结果给药组瘤重明显低于模型组（P〈0．05）,肿瘤组TNF－α水平明显高于空白对照组（P〈0．05）,均具有统计学意义。结论五味子乙素具有良好曲抗肿瘤活性。     

五味子乙素通过Traf6/TAK1信号通路介导人胃癌细胞凋亡

目的研究五味子乙素介导人胃癌HGC27细胞凋亡发生的作用及对Traf6/TAK1信号通路的影响。方法不同浓度的五味子乙素(12、24、48μg/ml)干预细胞后,采用CCK8法检测HGC27细胞增殖情况,流式细胞术分析五味子乙素诱导HGC27细胞发生凋亡的情况,免疫印迹法分析五味子乙素对HGC27细胞中Bax、Bcl-2、Traf6、TAK1及p-TAK1蛋白表达量的影响。结果与对照组比较,五味子乙素能显著抑制HGC27细胞增殖,诱导细胞凋亡;诱导促凋亡蛋白Bax表达,抑制抗凋亡蛋白Bcl-2蛋白表达;显著抑制Traf6、p-TAK1蛋白表达,且呈浓度依赖性,差异均有统计学意义(P <0. 05)。结论五味子乙素能明显抑制HGC27细胞增殖、诱导凋亡,其作用机制可能与抑制Traf6/TAK1信号通路活化有关。     

牡荆素的神经保护作用及机制研究进展

牡荆素是一种天然黄酮类化合物,具有广泛的药理活性。近年来研究发现其对中枢系统和周围神经系统具有明显的保护作用,包括抗记忆损伤、抗癫痫、抗缺血缺氧性脑损伤、抗抑郁、镇痛等作用。这些神经保护作用可能是通过降低自由基水平、对抗神经凋亡、调节炎症因子及其通路、调节神经递质及相关受体等多途径,多靶点的机制实现的。该文就近年来牡荆素的神经保护作用及相关作用机制的研究进展作简要概述。     

五味子乙素和γ-分泌酶抑制剂GSI联用对脑胶质瘤细胞增殖和凋亡的影响及其机制研究

目的　探讨五味子乙素和γ- 分泌酶抑制剂GSI 联用对人脑胶质瘤SHG-44 细胞增殖和凋亡的影响及其可能机制。方法　采用CCK8 实验检测25、50、100、200 mg/L 五味子乙素及2.5、5、10、20 μmol/L 的GSI 分别作用于人脑胶质瘤SHG-44 细胞24、48、72 h 后细胞的增殖情况，计算IC50 值；根据IC50 值选择最佳的五味子乙素及GSI 的作用浓度，将细胞分为对照组、五味子乙素组、GSI 组、五味子乙素+GSI 组，通过CCK8 试验检测细胞的增殖情况，流式细胞术检测细胞的凋亡情况，Western blot 检测Cleaved caspase3、Notch1、Hes1 蛋白的表达。结果　不同浓度的五味子乙素及GSI 处理细胞24、48、72h 后均能显著降低人脑胶质瘤SHG-44 细胞的存活率，并呈浓度和时间依赖性，选择60 mg/L 五味子乙素和10 μmol/L 的GSI 进行后续研究。五味子乙素组、GSI 组、五味子乙素+GSI 组细胞存活率及Notch1、Hes1 蛋白表达均显著低于对照组，细胞凋亡率及Cleaved caspase3 蛋白表达均显著高于对照组（P<0.01）；五味子乙素+GSI 组细胞存活率及Notch1、Hes1 蛋白表达均显著低于五味子乙素组和GSI 组，细胞凋亡率及Cleaved caspase3 蛋白表达均显著高于五味子乙素组和GSI 组（P<0.01）。结论　不同浓度五味子乙素和GSI 均能显著抑制人脑胶质瘤SHG-44 细胞增殖并促进其凋亡，而五味子乙素和GSI 联用对人脑胶质瘤SHG-44 细胞增殖和凋亡的影响大于单独使用五味子乙素和GSI，可能与其显著下调Notch1、Hes1 蛋白表达有关。     

五味子提取物及其有效成分对心血管疾病的药理作用研究进展

五味子是常用中药材之一，在保肝、治疗心脑血管疾病等方面发挥重要作用，其主要活性成分包括木脂素类、多糖类、挥发油及有机酸等成分。对五味子提取物及其有效成分治疗心血管疾病的抗心肌炎症、抗氧化损伤、抑制心肌细胞凋亡、缓解心肌纤维化等药理作用及其机制进行综述，发现五味子总木脂素可以调节核因子-κB信号通路、激活氮合酶途径抑制炎症因子及心肌细胞的凋亡，五味子乙素调节酪氨酸激酶2蛋白/信号转导子与激活子3信号通路抑制氧化损伤，五味子提取物抑制Smad蛋白信号传导发挥舒张心血管作用。     

双环醇的药理作用与临床应用近况

双环醇(百赛诺),是在五味子素的基础上人工合成的一类新药,具有明显的肝细胞保护作用和一定的抗肝炎病毒作用[1]。近年来,已广泛用于治疗病毒性肝炎和其他慢性肝病,取得了较好的疗效。现就其药理作用和临床应用状况作一综述。     

五味子乙素联合泼尼松调节PI3K/Akt信号通路改善大鼠膜性肾病研究

目的 研究五味子乙素联合泼尼松对膜性肾病大鼠的作用及对其对PI3K/Akt信号通路的影响。方法 取15只SD大鼠作为对照组,60只大鼠采用阳离子化牛血清白蛋白（C-BSA）建立膜性肾病模型,造模完成后的大鼠随机分为模型组、泼尼松（2 mg/kg）组、五味子乙素（30 mg/kg）组、五味子乙素（30 mg/kg） ＋泼尼松（2 mg/kg）组。连续给药28 d后,分别测定各组大鼠24 h尿蛋白量、血清总胆固醇（TC）、三酰甘油（TG）、丙二醛（MDA）、超氧化物歧化酶（SOD）、尿素氮（BUN）及肌酐（Scr）水平,苏木精-伊红染色法进行组织病理学检查,Western blotting法检测大鼠肾脏p-Akt、Akt、PI3K-P85、PI3K-P110蛋白表达水平。结果 与模型组比较,泼尼松组、五味子乙素组、五味子乙素＋泼尼松组大鼠24 h尿蛋白量和血清TC、TG、MDA、BUN及Scr水平均显著降低（P<0.05）,SOD水平显著升高（P<0.05）,组织病理学明显改善,肾脏p-Akt、Akt、PI3K-P85、PI3K-P110蛋白表达水平均显著降低（P<0.05）,且五味子乙素＋泼尼松组各项指标均优于单给药组。结论 五味子乙素联合泼尼松对大鼠膜性肾病发挥显著改善作用,作用优于单给药,其机制可能与调节PI3K/Akt信号通路有关。     

The protective mechanism of schisandrin A in d-galactosamine-induced acute liver injury through activation of autophagy

Context: The principal bioactive lignan of Schisandra chinensis fructus, commonly used for traditional Chinese medicine, is schisandrin A. Schisandrin A has been widely reported as being very effective for the treatment of liver disease. However, the mechanisms of its protective effects in liver remain unclear.

Objective: To explore the hepatoprotective mechanisms of schisandrin A.

Materials and methods: d-Galactosamine (d-GalN)-induced liver injury in mice was used as a model. Schisandrin A was examined for its protective mechanisms using hematoxylin–eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blotting and real-time PCR (RT-PCR).

Results: Aspartate amino-transferase (AST) and alanine transaminase (ALT) levels in the schisandrin A group were significantly decreased (p?d-GalN-treated group. HE results showed that the pathological changes in hepatic tissue seen in the d-GalN-treated were reduced in the schisandrin A/d-GalN-treated group, with the morphological characteristics being close to those of the control (untreated) group. Western blotting results showed that schisandrin A can activate autophagy flux and inhibit progression of apoptosis. The immune function of the schisandrin A-pretreated group was assayed by flow cytometry. It was found that the mechanism may involve activated autophagy flux, inhibited apoptosis, and improved immunity in response to liver damage.

Conclusion: Our results show that the hepatoprotective mechanisms of schisandrin A may include activation of autophagy flux and inhibition of apoptosis. These results provide pharmacological evidence supporting its future clinical application.     

Effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice with and without the influence of fenofibrate

Schisandrin B, an active ingredient isolated from the fruit of Schisandra chinensis, increased serum and hepatic triglyceride levels in mice. In the present study, the effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice without and with the influence of fenofibrate were investigated. Parameters on hepatic index (the ratio of liver weight to body weight × 100) were also analyzed. Mice were intragastrically treated with schisandrin B at a single dose of 0.2, 0.4, 0.8, or 1.6 g/kg, without or with fenofibrate pretreatment (0.1 g/kg/day for 4 days, p.o.). Twenty-four hours after schisandrin B treatment, serum/hepatic triglyceride and total cholesterol levels were measured. Schisandrin B treatment dose-dependently increased serum and hepatic triglyceride levels as well as hepatic index in mice. In contrast, hepatic total cholesterol levels were decreased in a dose-dependent manner in schisandrin B-treated mice. Data obtained from effective kinetics analysis indicated that the action of schisandrin B on serum triglyceride had a higher specificity than those on hepatic total cholesterol and hepatic index. While fenofibrate pretreatment inhibited the schisandrin B-induced elevation in serum triglyceride levels, it completely abrogated the elevation of hepatic triglyceride levels in schisandrin B-treated mice. The combined treatment with schisandrin B and fenofibrate decreased hepatic total cholesterol level and increased the hepatic index in an additive or semi-additive manner, respectively. In conclusion, the results of effective kinetics analysis indicated that the schisandrin B-induced hypertriglyceridemia was competitively inhibited by fenofibrate. Schisandrin B may offer the prospect of setting up a mouse model of hypertriglyceridemia and fatty liver for screening triglyceride-lowering drug candidates.     

Effects of schisandrin on transcriptional factors in lipopolysaccharide-pretreated macrophages

Schisandrin is the main active ingredient isolated from Schisandra chinensis Baill. Recent studies have demonstrated that schisandrin exhibits anti-inflammatory effects in vivo and in vitro. In this study, we examined whether the order of lipopolysaccharide (LPS) treatment affects the mechanism of schisandrin anti-inflammatory activity. We found that the antiinflammatory mechanisms are not the same depending on whether macrophages were treated with schisandrin before or after LPS. The main difference is that inhibitor kappaBα (IκBα) degradation was not inhibited when macrophages were pretreated by LPS before schisandrin and was weakly inhibited when macrophages were pretreated by schisandrin before LPS.     

Prevention and treatment of doxorubicin-induced cardiotoxicity by dexrazoxane and schisandrin B in rabbits

The cost of dexrazoxane, a drug used to provide protection from doxorubicin-induced cardiotoxicity, limits its use in low-income countries. We aimed to see whether schisandrin B, an inexpensive drug, could provide protection equivalent to that provided by dexrazoxane. New Zealand white rabbits were randomly divided into groups and treated with saline, doxorubicin, doxorubicin + dexrazoxane, or doxorubicin + schisandrin B. Doxorubicin-induced damage and the protective effects were studied by recording the echocardiographic parameters and serum levels of superoxide dismutase, malondialdehyde, cardiac troponin I, and brain natriuretic peptide and observing the histology and degree of apoptosis. Schisandrin B had dose-dependent effects in decreasing the magnitude of doxorubicin-induced indicators of cardiomyopathy to a degree that approximated the decrease produced by dexrazoxane treatment. Schisandrin B might be a useful, low-cost alternative drug for this application.     

五味子乙素联合顺铂对H22荷瘤小鼠存活时间的影响

目的:探讨五味子乙素(schisandrin B,SchB)联合顺铂对H22荷瘤小鼠存活时间影响机制。方法:将H22肿瘤细胞接种到昆明种小鼠的腹腔,建立H22小鼠腹水瘤模型,并对小鼠H22腹水瘤模型进行五味子乙素、顺铂和两者联合处理。结果:小鼠体内实验显示五味子乙素联合顺铂可明显减少腹水的产生,延长小鼠的存活时间。生命延长率为39.45%。结论:五味子乙素联合顺铂能更好地抑制H22移植瘤的增殖,并促进其凋亡,延长H22肿瘤小鼠的存活时间。     

A novel experimental model of acute hypertriglyceridemia induced by schisandrin B

Mice were intragastrically treated with single doses (0.05-0.8 g/kg) of schisandrin B (a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis). Twenty-four hours after schisandrin B administration, the serum triglyceride level was increased by 10-235% in a dose-dependent manner. However, the serum low density lipoprotein cholesterol level was significantly decreased by 28% at a dose of 0.8 g/kg. When given once daily (0.01-0.2 g/kg) for 4 days, schisandrin B also dose-dependently elevated the serum triglyceride level (17-134%). Kinetics parameters estimated by Scott's plot analysis of schisandrin B-induced changes in serum and hepatic triglyceride levels were determined: serum-E(max) (maximal effect)=6 mmol/L (384% increase, P<0.001); K(D) (affinity)=0.59 mmol/kg; pD(2) (an index of affinity)=6.62; liver-E(max)=21 micromol/g (68% increase, P<0.001); K(D)=0.37 mmol/kg; pD(2)=6.83. The efficacy of schisandrin B in increasing the triglyceride level was 5.6-fold higher in serum than in liver tissue. Fenofibrate (0.2g/kg) treatment, when in combination with schisandrin B (0.2g/kg), for 4 days significantly reduced the schisandrin B-induced increase in serum triglyceride level (by 81%, P<0.001). Hepatic triglyceride level was also decreased (by 100%, P<0.001) by co-treatment with fenofibrate. Our results suggest that schisandrin B treatment can be used to establish a mouse model of acute hypertrigylceridemia.     

Screening of herbal components for attenuating amiodarone-induced hepatotoxicity on gel-entrapped rat hepatocytes

Abstract

Amiodarone (AMD) is a hepatotoxic drug that has been widely used as a class III antiarrhythmic drug. Because, to date, only a few kinds of protectants are able to reduce AMD hepatotoxicity, this article utilized gel-entrapped rat hepatocytes to screen effective protectants from a series of herbal compounds for their effects against AMD-induced toxicity. Herbal compounds, including matrine, silibinin, glycyrrhizic acid, schisandrin B, epigallocatechin gallate and anisodamine, were cotreated with AMD to assess their protective effect, whereas vitamin E, which has been shown to be protective in rats, was selected as a control. It was found that vitamin E, as with its function in rats, provided the best protection in gel-entrapped rat hepatocytes, whereas silibinin, a major component of silymarin, could largely reduce AMD-induced hepatotoxicity, performing a similar function as silymarin in rats. The results illustrated that gel-entrapped hepatocytes may reflect the protective effects of drugs and serve as a reliable model for screening hepatoprotectants. Moreover, matrine, a widely used monomer of the traditional Chinese medicine, Sophora flavescens, for treatment of arrhythmia, was evidenced to show some effective protections against AMD hepatotoxicity. Taken together, gel-entrapped rat hepatocytes may provide a platform for screening effective candidates from the herbal component library.