Effects and mechanisms of silibinin on human hepatoma cell lines

AIM To investigate in vitro effects and mechanisms of silibinin on hepatocellular carcinoma (HCC) cell growth. METHODS Human HCC cell lines were treated with different doses of silibinin. The effects of silibinin on HCC cell growth and proliferation, apoptosis, cell cycle progression, histone acetylation, and other related signal transductions were systematically examined. RESULTS We demonstrated that silibinin significantly reduced the growth of HUH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells. Silibinin-reduced HuH7 cell growth was associated with significantly upregulated p21/CDK4 and p27/CDK4 complexes, downregulated Rb-phosphorylation and E2F1/DP1 complex. Silibinin promoted apoptosis of HuH7 cells that was associated with down-regulated survivin and upregulated activated caspase-3 and -9. Silibinin's anti angiogenic effects were indicated by down-regulated metalloproteinase-2 (MMP2) and CD34. We found that silibinin-reduced growth of HuH7 cells was associated with increased activity of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and decreased p-Akt production, indicating the role of PTEN/ PI3K/Akt pathway in silibinin-mediated anti-HCC effects. We also demonstrated that silibinin increased acetylation of histone H3 and H4 (AC-H3 and AC-H4), indicating a possible role of altered histone acetylation in silibininreduced HCC cell proliferation.CONCLUSION Our results defined silibinin's in vitro anti-HCC effects and possible mechanisms, and provided a rationale to further test silibinin for HCC chemoprevention.     

水飞蓟宾胶囊预防抗结核药物肝损害的临床观察

[摘要]目的:探讨水飞蓟宾胶囊在结核病治疗中预防药物肝损害的价值。方法:我院2007年7月~2009年1月期间住院治疗112例肺结核患者,治疗组(47例)在采取抗结核方案基础上应用水飞蓟宾胶囊（70mg,口服,tid）护肝,对照组(65例)未应用水飞蓟宾胶囊,采取抗结核方案与治疗组相同,观察两组肝功能损害的情况。结果:抗结核治疗期间治疗组发生肝功异常比例明显低于对照组,两组比较有统计学差异(P<0.05)。治疗组发生肝功能异常停用抗结核药物给予保肝治疗,肝功能恢复正常平均时间低于对照组,两组比较有统计学差异（P<0.05）。结论:结核病患者在常规抗结核治疗的同时应用水飞蓟宾胶囊可以降低肝损害的发生率,发生肝损害的程度也可减轻。     

拉米夫定、水飞蓟滨治疗乙肝肝硬化临床研究

目的探讨拉米夫定联合水飞蓟滨对治疗乙型肝炎肝硬化指标变化的影响。方法将64例乙型肝炎肝硬化患者随机分为治疗组和对照组,治疗最少12个月,在治疗前、治疗后半年及治疗前、治疗后12个月测定肝纤维化指标及肝功能指标,进行相关性比较分析。结果治疗组肝纤维化及肝功能指标下降明显优于对照组,差异具有统计学意义（P〈0．05）;同时其AST治疗组1年后与半年君比较AST下降明显,其疗效与疗程呈相关性。结论拉米夫定联合水飞蓟滨能明显改善乙肝肝硬化患者肝纤维化指标及肝功能指标。     

Silibinin Enhances Ultraviolet B-Induced Apoptosis in MCF-7 Human Breast Cancer Cells

Purpose

Chemotherapies for breast cancer generally have strong cellular cytotoxicity and severe side effects. Thus, significant emphasis has been placed on combinations of naturally occurring chemopreventive agents. Silibinin is a major bioactive flavonolignan extracted from milk thistle with chemopreventive activity in various organs including the skin, prostate, and breast. However, the mechanism underlying the inhibitory action of silibinin in breast cancer has not been completely elucidated. Therefore, we investigated the effect of silibinin in MCF-7 human breast cancer cells and determined whether silibinin enhances ultraviolet (UV) B-induced apoptosis.

Methods

The effects of silibinin on MCF-7 cell viability were determined using the MTT assay. The effect of silibinin on PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein expression in MCF-7 cells was analyzed using Western blot. The effect of silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry.

Results

A dose- and time-dependent reduction in viability was observed in MCF-7 cells treated with silibinin. Silibinin strongly induced apoptotic cell death in MCF-7 cells, and induction of apoptosis was associated with increased p53 expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells.

Conclusion

Silibinin induced a loss of cell viability and apoptotic cell death in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin might be an important supplemental agent for treating patients with breast cancer.     

水飞蓟宾对抗结核药物引起的肝功能损害的保护作用

目的：探讨水飞蓟宾对抗结核药物引起的肝功能损害患者进行预防性治疗后的肝脏的保护作用。方法：随机将病人两组,治疗组30例,对照组24例,治疗组在用抗结核药物的同时全程加服水飞蓟宾,对照组仅仅加用肝泰乐,观察两组肝损害的情况。结果：治疗组的发生肝损害的患者少于对照组,严重损害的患者也大大少于对照组,4周后,治疗组未在发生肝损害。两组比较X^2=7-095,P〈0-05,有统计学的差异。结论：水飞蓟宾对抗结核药物引起的肝功能损害有保护作用。     

水飞蓟宾联合复方二氯醋酸二异丙胺治疗非酒精性脂肪肝的临床研究

目的探讨水飞蓟宾联合复方二氯醋酸二异丙胺治疗非酒精性脂肪肝的临床疗效。方法选取2015年9月—2016年6月在驻马店市中心医院进行治疗的86例非酒精性脂肪肝患者,根据治疗方案不同分为对照组(43例)和治疗组(43例)。对照组患者口服复方二氯醋酸二异丙胺片,2片/次,3次/d。治疗组在对照组的基础上口服水飞蓟宾胶囊,3粒/次,3次/d。两组患者均连续治疗8周。观察两组患者的临床疗效,同时比较两组治疗前后肝功能、血脂水平和血清学指标变化情况。结果治疗后,对照组和治疗组总有效率分别为72.09%和88.37%,两组总有效率比较差异有统计学意义(P0.05)。治疗后,两组患者三酰甘油(TG)、胆固醇(TC)及丙氨酸转氨酶(ALT)和天氨酸转氨酶(AST)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组降低程度优于对照组,两组比较差异具有统计学意义(P0.05)。与治疗前相比,治疗后两组血清肿瘤坏死因子-α(TNF-α)、白细胞介素-18(IL-18)及降钙素原(PCT)均明显降低,IL-10则明显升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组上述指标改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。结论水飞蓟宾联合复方二氯醋酸二异丙胺治疗非酒精性脂肪肝效果显著,可明显改善患者肝功能及血脂水平,并降低机体炎症反应,具有一定的临床推广应用价值。     

Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells

Ethnopharmacological relevance

The expression of matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) are pivotal steps in breast cancer pathogenesis. In a previous study, we reported that silibinin suppresses TPA-induced MMP-9 expression through the Raf/MEK/ERK pathway.

Aims of the study

Herein we determined the co-relationship between MMP-9 and COX-2, as well as the effect of silibinin on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and COX-2 expression in the human breast cancer cells, MCF-7 and MDA-MB231.

Methods

The toxicity of silibinin was evaluated by Quick Cell Proliferation Assay Kit II. MMP-9 and COX-2 expression were analyzed by Zymography and Western blotting, respectively. Adenoviral constitutively active (CA)-MEK was used to activate MEK/ERK pathway.

Results

The expression of MMP-9 and COX-2 in response to TPA was increased, whereas TPA-induced MMP-9 and COX-2 expression was decreased by silibinin. Our results showed that TPA-induced MMP-9 expression was inhibited by celecoxib in a dose-dependent fashion, but not MMP-1-expression. Both MMP-9 and COX-2 expression were significantly increased by CA-MEK overexpression. In contrast, TPA-induced MMP-9 and COX-2 expression was decreased by UO126 (MEK1/2 inhibitor).

Conclusion

Silibinin down-regulates TPA-induced MMP-9 expression through inhibition of COX-2 expression in breast cancer cells.     

Consumption of silibinin, a flavonolignan from milk thistle, and mammary cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma (TAg) mouse

Silibinin is a flavonolignan extracted from milk thistle with cancer chemopreventive activity in preclinical models of prostate and colorectal cancer. A milk thistle extract, of which silibin is a major component, has recently been shown to exacerbate mammary carcinogenesis in two rodent models. We tested the hypothesis that consumption of silibinin or silipide, a silibinin formulation with pharmaceutical properties superior to the unformulated agent, affect breast cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma mouse model. Mice received silibinin or silipide (0.2% silibinin equivalents) with their diet from weaning, and tumour development was monitored by weekly palpation and the number and weight of neoplasms at the end of the experiment. Intervention neither promoted, nor interfered with, tumour development. The result suggests that promotion of carcinogenesis is not a feature of silibinin consistent across rodent models of mammary carcinogenesis.     

水飞蓟宾胶囊治疗抗艾滋病毒药物致肝损害的效果观察

目的 观察水飞蓟宾胶囊对艾滋病患者抗病毒治疗后出现肝损害的疗效.方法 将82例诊断为因高效抗逆转录病毒治疗后出现药物性肝炎的艾滋病初治患者随机分成对照组40例和治疗组42例,对照组予口服葡醛内酯片（每次0.2 g tid）;治疗组在此基础上加用口服水飞蓟宾胶囊（每次70 mg tid）,疗程2周.结果 治疗后两组患者的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷氨酰转肽酶（GGT）均明显下降,治疗组总有效率与对照组相比差异有统计学意义（P 〈 0.05）,而且治疗组的ALT、AST、GGT恢复率与对照组相比差异有统计学意义（P 〈 0.05）.结论 水飞蓟宾治疗抗艾滋病病毒药物引起的药物性肝炎疗效显著,且用药安全.