Preparation of tritium‐labeled Silybin—a protectant for common liver diseases

Silymarin, the seed extract of milk thistle plant, Silybum marianum, has been used traditionally for the treatment of liver diseases and bile duct infection. Silybin 1 is the main bioactive components of silymarin, consisting a pair of diastereomers: Silybin A and Silybin B. In this article, we report the preparation of tritium‐labeled Silybin, which was accomplished by protection of Silybin as tritylated compound 2 and followed by oxidation of the primary alcohol to its corresponding aldehyde 3 . Subsequent reduction with NaB[³H]₄ and deprotection of the trityl group provided the tritium‐labeled Silybin 4 . Copyright © 2006 John Wiley & Sons, Ltd.     

水飞蓟宾胶囊对异烟肼和利福平肝损害小鼠的保护作用

目的：观察水飞蓟宾胶囊(SC)对异烟肼(INH)与利相干(RFP)合用致肝损伤小鼠的保护作用。方法：测定肝损伤小鼠在给予SC后肝指数、血清谷丙转氨酶(ALT)的活性，肝匀浆中谷胱甘肽(GSH)及丙二醛(MDA)的含量，肝微粒体中细胞色素P450含量及其亚型2E1的活性。结果：SC可对抗INH和RFP合用引起的肝指数、血清ALT水平、肝匀浆中的MDS含量及P450、4502E1活性的升高，增加GSH含量；病理学检查SC能明显减轻肝细胞的变性和坏死。结论：SC对INH和RFP肝毒性的保护作用与其稳定肝细胞膜、抑制脂质过氧化反应、清除自由基、抑制药物代谢酶有关。     

护肝宁片联合水飞蓟宾对脂肪肝患者血脂及血管内皮素-1的影响

目的观察护肝宁片联合水飞蓟宾治疗脂肪肝的疗效,探讨其对血管内皮素-1(ET-1)的影响。方法将我院收治的脂肪肝患者随机分为2组,即水飞蓟宾组及护肝宁片联合水飞蓟宾治疗组(联合治疗组),分别给予水飞蓟宾、护肝宁片联合水飞蓟宾治疗。检测两组治疗前后TC、TG、LDL、ALT、AST、γ-GT、ET-1水平。另选20例健康成年人作为健康对照组,检测其血清ET-1水平。结果治疗后,水飞蓟宾组、联合治疗组血清TC、TG、LDL、ALT、AST、γ-GT水平明显降低(P<0.05),但联合治疗组减低更明显(P<0.05)。与健康人群相比,联合治疗组血清内皮素-1水平明显增高,治疗后,水飞蓟宾组、联合治疗组血清内皮素-1水平均明显降低(P均<0.05)。水飞蓟宾组总有效率为87.5%,联合治疗组总有效率为96.12%,两组比较差异有统计学意义(P<0.05)。结论护肝宁联合水飞蓟宾治疗脂肪肝疗效显著,脂肪肝患者ET-1明显增高,ET-1可能参与脂肪肝的病理生理过程。     

HPLC法测定水飞蓟素滴丸的含量

目的 建立水飞蓟素滴丸中的水飞蓟宾的HPLC含量测定法。方法 采用HPLC法,以Shimadzu VP-ODS C₁₈为色谱柱,以甲醇-水-0.5 mol·L^-1磷酸二氢钾溶液(260 ml∶240 ml∶25 ml)为流动相,用0.2 mol·L^-1磷酸调节pH至5.3,流速为1 ml·min^-1。检测波长为288 nm。结果 水飞蓟宾的量在0.152～0.912μg范围内线性良好,回收率为102.0%,RSD为0.72%。结论 该方法简便、可靠,适用水飞蓟素滴丸的质量控制。     

水飞蓟化学成分的研究

从引种水飞蓟[Silybum marianum(L.)Gaertn.]的果实中分离得到两种黄酮木脂素化合物。通过光谱分析,鉴定为水飞蓟宾(Silybin)和水飞蓟宁(Silydianin)。     

Amatoxin poisoning treatment decision-making: Pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis

Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing mushroom species. In addition to absence of antidote, no chemotherapeutic consensus was reported. The aim of the present study is to perform a retrospective multidimensional multivariate statistic analysis of 2110 amatoxin poisoning clinical cases, in order to optimize therapeutic decision-making. Our results allowed to classify drugs as a function of their influence on one major parameter: patient survival. Active principles were classified as first intention, second intention, adjuvant or controversial pharmaco-therapeutic clinical intervention. We conclude that (1) retrospective multidimensional multivariate statistic analysis of complex clinical dataset might help future therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and putatively ceftazidime are clearly associated, in amatoxin poisoning context, with higher level of patient survival.     

The Effect of a Silybin-Vitamin E-Phospholipid Complex on Nonalcoholic Fatty Liver Disease: A Pilot Study

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-β, tumor necrosis factor-α, degree of steatosis, and γ-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage. Other members of the Real Sud Group: L. Cimino, Federico II University, Naples; V. De Girolamo and A. Marone, Ascalesi Hospital, Naples; C. De Stefano, S. Carlo Hospital, Potenza; G. De Stefano, Madonna delle Grazie Hospital, Matera; D. Disalvo and B. Provenzano, Villa D’Agri Hospital, Potenza; P. Esposito and A. Simonetti, Second University, Naples; M. D. Iannece and R. Pempinello, Cotugno Hospital, Naples; R. Iorio, Giugliano Hospital, Naples; S. Monastra and M. Di Pierro, S. Gennaro Hospital, Naples.     

水飞蓟宾磷脂复合物对慢性乙型肝炎患者血清细胞因子及肝纤维化指标的影响

目的观察水飞蓟宾磷脂复合物对慢性乙型肝炎患者肝纤维化指标及细胞因子的影响。方法83例慢性乙型肝炎患者按就诊顺序随机分为对照组（n=42）和观察组（n=41）,对照组采用常规保肝和支持治疗,观察组在对照组基础上加用水飞蓟宾磷脂复合物105mg/次,3次／d,治疗前后检测肝功能,用酶联免疫吸附法检测血清转化生长因子β（TGF-β）、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）,应用放射免疫法检测血清纤维化指标透明质酸（HA）、Ⅲ型前胶原（PCⅢ）、层粘连蛋白（LN）、Ⅳ型胶原（CⅣ）。结果观察组治疗后血清TGF—β（174．4±49．7）μg/L、TNF—α（89．5±25．8）μg/L、IL-6（232．6±61．7）μg/L及HA（180±54）μg/L、PCⅢ（171±49）μg/L、LN（168±39）μg/L、C1V（153±37）μg/L水平较治疗前及对照组治疗后均显著降低（P〈0．05）。结论水飞蓟宾磷脂复合物通过影响慢性乙型肝炎患者血清细胞因子等发挥抗肝纤维化作用。     

Failure of Intravenous Silibinin Monotherapy to Prevent Hepatitis C Genotype 2A Liver Graft Reinfection

Background

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) remains a serious problem in the clinical management of post-oLT patients. Recently, two case reports have described successful prevention of HCV liver graft reinfection with intravenous silibinin (SIL) monotherapy in two carriers of genotype 3a and 1a/4 HCV. Based on these findings, we decided to offer such a therapy to a 65 year old woman on the oLT list.

Case Presentation

A 65 year old patient with HCV 2a cirrhosis, a previous relapse to PegIFn and Rbv therapy, was listed for oLT due to hepatocellular carcinoma. She started SIL monotherapy 24 hours before oLT. After an initial HCV-RnA decline following surgery,a progressive HCV RnA increase was observed. For this reason, SIL was stopped after 15 days of monotherapy.

Conclusions

SIL has multiple anti-HCV mechanisms of action, most of them have been characterized in vitro only. Our case report shows that the antiviral effect of SIL might be HCV genotype dependent, as recently suggested by a study, showing no effect of SIL on the HCV-2a subgenomic replicon model. our case reinforces the need for controlled studies to assess the efficacy of silibinin therapy in HCV infected patients before it can be broadly used in all clinical settings.     

水飞蓟宾对实验兔球囊血管损伤后内膜增生的影响

探讨水飞蓟宾对兔球囊血管损伤后内膜增生的影响。将新西兰大白兔随机分为对照组 (n =6 )、小剂量水飞蓟宾组 [n =8,2 0mg (kg·d) ]、大剂量水飞蓟宾组 [n =8,4 0mg (kg·d) ]。用球囊导管对实验兔行髂动脉损伤 ,用药组于术前 3d分别用小剂量及大剂量水飞蓟宾 ,术后 2 8d取病变血管染色并免疫组织化学检查 ,以计算机图像分析系统分析血管内膜、中膜厚度和腔面积的变化 ,计算内膜增生细胞核抗原增殖指数。结果发现 ,小剂量水飞蓟宾对血管内膜和中膜厚度、腔面积、内膜增生细胞核抗原阳性细胞百分比无明显影响 (P >0 .0 5 ) ;大剂量水飞蓟宾使腔面积扩大、内膜厚度减少、内膜增生细胞核抗原阳性细胞百分比减少 (P <0 .0 5 )。提示水飞蓟宾能抑制血管内膜增生 ,有可能用于防治再狭窄。