水飞蓟素联合二甲双胍治疗肥胖型非酒精性脂肪肝疗效分析

目的分析水飞蓟素联合二甲双胍对肥胖型非酒精性脂肪肝患者的治疗作用。方法符合诊断标准的肥胖型非酒精性脂肪肝患者48例分为两组，试验组24例联合水飞蓟素及二甲双胍治疗，对照组24例服用水飞蓟素及维生素C片治疗，疗程均为4～6月。治疗前后测定各组患者血清转氨酶水平（ALT、AST）、血脂水平（TG、TC、LDL-C及HDL-C）、血清TNFα水平、胰岛素抵抗指数（IRI）及肝／脾CT比值并作统计学处理，同时观察实验过程中出现的不良反应。结果治疗后两组患者血清ALT均明显降低，其中尤以试验组降低明显（P〈0．01）；试验组患者治疗后各项血脂水平均显著改善；试验组胰岛素抵抗指数于治疗后明显下降（P〈0．05），而对照组无明显改变（P〉0．05）；两组患者治疗后血清TNFα均明显下降，尤以试验组下降明显（P〈0．01）；同时试验组治疗后肝／脾CT比值显著升高（P〈0．01）。用药期间两组患者均未出现显著不良反应。结论水飞蓟素联合二甲双胍对肥胖型非酒精性脂肪肝有显著疗效且用药安全。     

Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats

BackgroundSilymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes.MethodThe liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5% sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats.ResultsThe conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension.ConclusionConventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.     

Efficacy and safety of iron chelators in thalassemia and sickle cell disease: a multiple treatment comparison network meta-analysis and trial sequential analysis

Background: To compare the efficacy and safety of desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) and silymarin in patients with either thalassemia or sickle cell disorder through network meta-analysis.

Methods: Electronic databases were searched for appropriate randomized clinical trials comparing iron chelators in patients with iron overload. Random effects model was used to generate direct, indirect and mixed treatment comparison pooled estimates for the following outcomes: serum ferritin, liver iron concentration (LIC), changes in serum ferritin, mortality, urine iron excretion, adverse events, neutropenia, agranulocytosis and number of patients withdrawing the chelating therapy.

Results: Thirty-two clinical trials were included in the meta-analysis. DFX/DFO was associated with better serum ferritin levels compared to DFO, DFX, DFO/Silymarin and DFP/DFO. DFX/DFO also lower LIC significantly compared to DFO. DFP/DFO was associated with higher LVEF, low risk of adverse events and reduced end of serum ferritin compared to DFO. Combination of silymarin with either DFP or DFX was observed with reduced end of treatment serum ferritin compared to using either of the drugs alone. DFP was observed with better effects in sickle cell disease. The strength of evidence was very low for most of the comparisons.

Conclusion: Relative estimates between the individual iron chelators have been established. However, this evidence should be considered preliminary and may change with the results of future head-to-head clinical trials.     

Silymarin improved 6-OHDA-induced motor impairment in hemi-parkisonian rats: behavioral and molecular study

Background

Neuroinflammation and oxidative stress has been shown to be associated with the development of Parkinson disease (PD). In the present study, we investigated the effect of intraperitoneal (i.p.) administration of silymarin, on 6-OHDA-induced motor-impairment, brain lipid per-oxidation and cerebrospinal fluid (CSF) levels of inflammatory cytokine in the rats.

Results

The results showed that silymarin is able to improve motor coordination significantly (p < 0.001) in a dose dependent manner. There was a significant (p < 0.001) increase in MDA levels of 6-OHDA-lesioned rats whereas; in silymarin (100, 200 and 300 mg/kg, i.p. for 5 days) pre-treated hemi-parkinsonian rats MDA levels was decreased markedly (p < 0.001). Furthermore the CSF levels of IL-1β was decreased (p < 0.001) in silymarin (100, 200 and 300 mg/kg) pre-treated rats up to the range of normal non-parkinsonian animals.

Conclusion

We found that pre-treatment with silymarin could improve 6-OHDA-induced motor imbalance by attenuating brain lipid per-oxidation as well as CSF level of IL-1β as a pro-inflammatory cytokine. We suggest a potential prophylactic effect for silymarin in PD. However, further clinical trial studies should be carried out to prove this hypothesis.     

水飞蓟素对非酒精性脂肪性肝炎大鼠小肠组织抗氧化作用的实验研究

目的探讨水飞蓟素对NASH大鼠小肠组织氧化应激损伤的影响。方法 50只Wistar大鼠被随机分为对照组、模型组和水飞蓟素干预组;对照组（10只）用普通饲料喂养,模型组（20只）通过高脂饮食建立NASH模型,水飞蓟素组（20只）给予高脂饮食加水飞蓟素灌胃,12周后评估。结果模型组较正常对照组大鼠血清TG、TC、ALT、AST水平明显升高（P〈0.01）,水飞蓟素组TG、TC、ALT、AST水平较模型组降低,差别有统计学意义（F=36.626～64.327,P〈0.01）;模型组大鼠较正常对照组小肠组织匀浆SOD活性明显降低（83.29±10.32U/mgprot对52.34±7.09U/mgprot）,MDA含量明显升高（0.56±0.07 Nmol/mgprot对0.97±0.09 Nmol/mgprot）,水飞蓟素组SOD活性较模型组有所升高,MDA水平下降,差异有统计学意义（F=23.488和10.609,P〈0.05）;内毒素水平为模型组（0.316±0.020EU/ml）〉水飞蓟素组（0.279±0.022EU/ml）〉正常对照组（0.234±0.021EU/ml）s;IgA水平为模型组〈水飞蓟素组〈正常对照组。结论抗氧化剂水飞蓟素不仅能提高肝脏本身的抗氧化能力,亦可以通过提高肠道抗氧化能力进而加强肠道的屏障作用。     

Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats

Adriamycin is a potent anticancer agent, its clinical use is limited for its marked cardiotoxicity and nephrotoxicity. The present study aimed to investigate the possible protective role of the natural antioxidant silymarin on ADR-induced heart and kidney toxicity. Studies were performed on four groups of rats. 1--control group, 2--silymarin group (50 mg/kg), 3--adriamycin group (10 mg/kg), 4--adriamycin+silymarin group. On the third day after ADR injection, plasma was separated for determination of LDH, CPK, cholesterol and total lipids. 30 days after ADR injection, plasma was separated for determination of creatinine and urea levels. Frozen heart specimens (72 h) and frozen kidney specimens (30days) were used for estimation of lipid peroxides and GSH contents. Histopathological examinations of heart and kidney sections were also done. Pretreatment of ADR-treated rats with silymarin resulted in a significant decrease in the plasma CPK, LDH, creatinine and urea. On the other hand silymarin pretreatment did not change ADR-induced hyperlipidemia. Silymarin pretreatment significantly decreased the myocardial MDA contents. In addition, silymarin pretreatment normalized renal tissue contents of MDA and GSH. Histopathological examination of heart and kidney sections revealed that ADR caused only mild myocardial injury in silymarin pretreated rats. Also, silymarin pretreatment inhibited ADR-induced renal tubular damage in rats. These results have suggested that, silymarin ameliorated ADR-induced cardiotoxicity and protected against ADR-induced nephrotoxicity in male albino rats. The mechanisms of silymarin induced protection against ADR-induced toxicities were proved to be due to inhibition of lipid peroxidation and protection against GSH depletion.     

Silymarin enhanced cytotoxic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells

Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which has anti-inflammatory, cytoprotective as well as antioxidant effects. Our previous study demonstrated that silymarin has anti-apoptotic effect against UV irradiation. In this study, we assessed the effect of silymarin on anti-Fas agonistic antibody CH11-treated human malignant melanoma, A375-S2 cells. Pretreatment with silymarin (3 × 10^- 4 mol/L) significantly induced cell apoptosis in CH11-treated A375-S2 cells. Mitochondrial transmembrane potential (ΔΨ_m) was also down-regulated by silymarin pretreatment. Caspase-8, -9, -3 and pan-caspase inhibitors partially reversed silymarin-induced apoptosis of CH11-treated cells. The expression of Fas-associated proteins with death domain (FADD), a downstream molecule of the death receptor pathway, was increased by silymarin pretreatment, followed by cleavage of procaspase-8, whose activation induced cell apoptosis. Moreover, cleavage of procaspase-3 and digestion of its substrate, the inhibitor of caspase-activated DNase (ICAD), were also increased by silymarin pretreatment. These results suggested that silymarin could also exaggerate the apoptotic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells.     

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。     

Chemopreventive Effects of a Flavonoid Antioxidant Silymarin on N-Butyl-N-(4- hydroxybutyl)nitrosamine-induced Urinary Bladder Carcinogenesis in Male ICR Mice

The modifying effects of dietary administration of a flavonoid antioxidant, silymarin, a mixture of three flavonoids isolated from milk thistle seeds, on N -butyl-. N -(4-hydroxybutyl)nitrosamine (OH- BBN)-induced urinary bladder carcinogenesis were examined in male ICR mice. Animals were divided into 5 groups, and groups 1 to 3 were given OH-BBN (500 ppm) in drinking water for 6 weeks. Mice in group 2 were fed a diet containing 1000 ppm silymarin for 8 weeks during the initiation phase starting 1 week before OH-BBN exposure, and mice in group 3 were fed the diet for 24 weeks during the postinitiation phase. Animals in group 4 were given only the test compound, and those in group 5 were given the basal diet alone throughout the experiment. Animals were sacrificed at the end of week 32. The frequency of bladder lesions, cell proliferation and cell cycle progression activity estimated in terms of the 5-bromodeoxyuridine (BrdU) labeling index or cyclin Dl-positive cell ratio were compared among the groups. Administration of silymarin in the initiation or postinitiation phase significantly decreased the incidences of bladder neoplasms and preneoplastic lesions. Dietary exposure to this agent significantly reduced the labeling index for BrdU and the cyclin Dl-positive cell ratio in various bladder lesions. These findings suggest that silymarin is effective in preventing OH-BBN-induced bladder carcinogenesis in mice.