水飞蓟宾及其衍生物生物活性及作用机制的研究进展

水飞蓟宾从水飞蓟Silybum marianum的种子中提取分离得到,属于黄酮木脂素类化合物,临床上常用于治疗急、慢性肝炎或肝功能异常的恢复。近年来研究发现水飞蓟宾具有抗肿瘤和抗代谢功能失调作用,通过调节活性氧水平实现对肿瘤的抑制作用,对糖尿病的治疗作用主要是通过保护靶器官和提高胰高血糖素样肽受体的表达实现的。对水飞蓟宾及其衍生物在治疗肝病、肿瘤、糖尿病等方面的生物活性及作用机制的研究进展进行综述,为深入研究水飞蓟宾及其衍生物的生物活性以及拓展其临床应用提供依据。     

Silymarin treatment of viral hepatitis: a systematic review

Silymarin from the milk thistle herb (Silybum marianum) is used by many patients with chronic viral hepatitis, but its efficacy remains unknown. We performed a systematic review of silymarin for the treatment of chronic viral hepatitis B and C. An exhaustive search strategy identified 148 papers that studied silymarin compounds in liver disease. Of these, four trials included patients with hepatitis C, one included hepatitis B patients, and two, unspecified chronic viral hepatitis. However, only one trial exclusively studied patients with hepatitis C, and none involved patients with only hepatitis B. Silymarin treatment resulted in a decrease in serum transaminases compared with baseline in four studies, and compared with placebo in only one study. There is no evidence that silymarin affects viral load or improves liver histology in hepatitis B or C. No studies were found that investigated the use of silymarin concomitantly with interferon, nucleoside analogues, or other conventional treatments for hepatitis B or C. In conclusion, silymarin compounds likely decrease serum transaminases in patients with chronic viral hepatitis, but do not appear to affect viral load or liver histology. Nevertheless it may be worthwhile to determine its effects in conjunction with standard antiviral treatment.     

黄酮并木脂素类化合物的研究进展

目的对黄酮并木脂素类化合物研究进展进行综述。方法查阅国内外相关文献40篇,从植物分布、结构类型、生物活性、结构研究方法等方面对黄酮并木脂素类化合物的研究进展进行综述。结果黄酮并木脂素类化合物分布广泛,结构类型多样,且具有保肝、抗氧化、抗心血管疾病等生物活性。结论为黄酮并木脂素的研究开发提供参考。     

Analysis of silibinin in rat plasma and bile for hepatobiliary excretion and oral bioavailability application

Silibinin is an herbal ingredient isolated from milk thistle. The aim of this study was to develop a simple liquid chromatographic system to assay silibinin in plasma and bile for pharmacokinetic study. Silibinin was given oral and intravenously. The plasma sample (25 microL) was vortex-mixed with 50 microL of internal standard solution (naringenin 10 microg/mL in acetonitrile) to achieve protein precipitation. Silibinin in the rat plasma and bile was separated using a reversed-phase C18 column (250 mm x 4.6 mm, 5 microm) with a mobile phase of acetonitrile -10 mM monosodium phosphate (pH 5.45 adjusted with orthophosphoric acid) (50:50, v/v) and the flow-rate of 1 mL/min. The UV detection wavelength was 288 nm. The concentration-response relationship from the present method indicated linearity over a concentration range of 0.5-100 microg/mL. Intra- and inter-assay precision and accuracy of silibinin fell well within the predefined limits of acceptability (<15%). An ultrafiltration method was used in this experiment and the protein binding of silibinin was 70.3+/-4.6%. After silibinin administration in rats, the disposition of silibinin in the plasma and bile fluid was due to rapid distribution and equilibration between the blood and hepatobiliary system, and the bile levels of unconjugated silibinin and total silibinin were greater than those in the plasma. The oral bioavailability of silibinin in rats was estimated to be 0.73%.     

Rapid separation and characterization of active flavonolignans of Silybum marianum by ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry

Ultra-performance liquid chromatography (UPLC) interfaced with the electrospray ionization (ESI) tandem mass spectrometer (MSⁿ) was developed for the simultaneous determination of silychristins A (1) and B (2), silydianin (3), silybins A (4) and B (5), and isosilybins A (6) and B (7), major bioactive flavonolignans in silymarin, a herbal remedy derived from the milk thistle Silybum marianum. In this study, the seven major active flavonolignans including the diastereomers 1/2, 4/5, and 6/7 were completely separated using UPLC with an ACQUITY UPLC C₁₈ column and a MeOH/water/formic acid mobile phase system. The collision-induced dissociation (CID) MSⁿ spectra of these flavonolignans were studied systematically using ESI-MS. The results with the present methodology show that UPLC–MSⁿ can be useful for general screening of active natural products from plant extracts and for the specific quality control of silymarin.     

水飞蓟发状根培养体系的建立及其水飞蓟宾含量的测定

实验采用6种发根农杆菌R1601,R15834,R1000,A4,R1025,R1感染水飞蓟植体,诱导水飞蓟发状根及其水飞蓟宾的产生。6种发根农杆菌均能诱导水飞蓟产生发状根,A4表现出较强的对水飞蓟的感染能力。实验通过侵染时间、预培养、共培养、pH等因素确定了诱导水飞蓟发状根产生的条件,确定MS液体培养基适合水飞蓟发状根的增殖。经过PCR分子鉴定,发根农杆菌中的DNA质粒成功的整合到转化根的基因组中。使用液相色谱测定了水飞蓟发状根中水飞蓟宾含量是水飞蓟植物中的2.5倍。实验所建立的水飞蓟发状根培养系统,为研究水飞蓟发状根大量培养生产水飞蓟宾奠定了基础。     

水飞蓟栽培研究进展

水飞蓟silybum marianum作为一种保肝护胆良药的原料植物,受全世界人们的关注,果实内水飞蓟素得到广泛的开发与利用,水飞蓟油和水飞蓟蛋白也有了初步的研究,国内对水飞蓟原料需求呈上升趋势,许多地区已大面积种植。本文对水飞蓟的生物学特性、栽培技术及生物技术应用的研究现状进行综述,并提出了相关建议。     

当飞利肝宁胶囊治疗非酒精性单纯性脂肪肝患者113例临床研究

目的 评价当飞利肝宁胶囊治疗湿热内蕴型非酒精性单纯性脂肪肝的有效性和安全性. 方法 选择非酒精性单纯性脂肪肝湿热内蕴证患者230例,符合全分析集(full analysis set,FAS)患者227例,其中当飞利肝宁胶囊组(试验组)113例,安慰剂组(对照组)114例,疗程均为12周,以治疗后肝/脾CT比值变化、肝/脾CT比值复常率以及中医证候评价有效性,以不良反应、实验室检查及心电图评价安全性.结果 两组治疗后肝/脾CT值较治疗前差异有统计学意义(P＜0.01),两组治疗后比较差异有统计学意义(P＜0.01).试验组肝/脾CT比值复常率为47.79％(54/113),优于对照组的22.81％(26/114),组间比较差异具有统计学意义(P＜0.01).试验组总有效率为76.11％,对照组为55.26％,两组比较差异有统计学意义(P＜0.01).两组治疗后脘腹痞闷、口干口苦评分较治疗前降低(P＜0.01);并且试验组治疗后明显低于对照组(P＜0.01).试验组治疗后丙氨酸氨基转移酶(ALT)较治疗前降低(P＜0.01),对照组ALT较治疗前也有降低但差异无统计学意义(P＞0.05),治疗后两组患者其他肝功能及血脂指标较治疗前比较差异均无统计学意义(P＞0.05).结论 当飞利肝宁胶囊对非酒精性单纯性脂肪肝湿热内蕴证患者有较好的治疗作用,临床应用安全.     

Hepatoprotective effect of silymarin

The use of medicinal plants in treating illnesses has been reported since ancestral times.In the case of hepatic diseases,several species such as Silybum marianum,Phyllanthus niruri,and Panus giganteus(Berk.)have been shown to ameliorate hepatic lesions.Silymarin is a natural compound derived from the species Silybum marianum,which is commonly known as Milk thistle.This plant contains at least seven flavoligands and the flavonoid taxifolin.The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol,acetaminophen,and carbon tetrachloride.The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation.Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver.It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity.A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.