Preparation of Sustained-release Silybin Microspheres by Spherical Crystallization Technique

Aim To improve the dissolution rate and bioavailability of silybin. Methods Sustained-release silybin microspheres were prepared by the spherical crystallization technique with soliddispersing and release-retarding polymers. A differential scanning calorimeter and an X-ray diffractometer were used to investigate the dispersion state of silybin in the microspheres. The shape, surface morphology, and internal structure of the microspheres were observed using a scanning electron microscope. Characterization of the microspheres, such as average diameter, size distribution and bulk density of the microspheres was investigated. Results The particle size of the microspheres was determined mainly by the agitation speed. The dissolution rate of silybin from microspheres was enhanced by increasing the amount of the dispersing agents, and sustained by the retarding agents. The release rate of microspheres was controlled by adjusting the combination ratio of the dispersing agents to the retarding agents. The resuits of X-ray diffraction and differential scanning calorimetry analysis indicated that silybin was highly dispersed in the microspheres in amorphous state. The release profiles and content did not change after a three-month accelerated stability test at 40 ℃ and 75% relative humidity. Conclusion Sustained-release silybin microspheres with a solid dispersion structure were prepared successfully in one step by a spherical crystallization technique combined with solid dispersion technique. The preparation process is simple, reproducible and inexpensive. The method is efficient for designing sustained-release microspheres with water-insoluble drugs.

Silybin counteracts lipid excess and oxidative stress in cultured steatotic hepatic cells

AIM: To investigate in vitro the therapeutic effect and mechanisms of silybin in a cellular model of hepatic steatosis.METHODS: Rat hepatoma FaO cells were loaded with lipids by exposure to 0.75 mmol/L oleate/palmitate for 3 h to mimic liver steatosis. Then, the steatotic cells were incubated for 24 h with different concentrations (25 to 100 μmol/L) of silybin as phytosome complex with vitamin E. The effects of silybin on lipid accumulation and metabolism, and on indices of oxidative stress were evaluated by absorption and fluorescence microscopy, quantitative real-time PCR, Western blot, spectrophotometric and fluorimetric assays.RESULTS: Lipid-loading resulted in intracellular triglyceride (TG) accumulation inside lipid droplets, whose number and size increased. TG accumulation was mediated by increased levels of peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding protein-1c (SREBP-1c). The lipid imbalance was associated with higher production of reactive oxygen species (ROS) resulting in increased lipid peroxidation, stimulation of catalase activity and activation of nuclear factor kappa-B (NF-κB). Incubation of steatotic cells with silybin 50 μmol/L significantly reduced TG accumulation likely by promoting lipid catabolism and by inhibiting lipogenic pathways, as suggested by the changes in carnitine palmitoyltransferase 1 (CPT-1), PPAR and SREBP-1c levels. The reduction in fat accumulation exerted by silybin in the steatotic cells was associated with the improvement of the oxidative imbalance caused by lipid excess as demonstrated by the reduction in ROS content, lipid peroxidation, catalase activity and NF-κB activation.CONCLUSION: We demonstrated the direct anti-steatotic and anti-oxidant effects of silybin in steatotic cells, thus elucidating at a cellular level the encouraging results demonstrated in clinical and animal studies.

Synthesis and Antioxidant Properties of Novel Silybin Analogues

Eight novel silybin analogues （7a-h） were synthesized and their antioxidant properties including the capability of scavenging superoxide anion free radicals and the inhibitory effect on DPPH free radicals were determined. Several synthetic compounds showed comparable antioxidative effect to that of quercetin.

Preparation of silybin 23-esters and evaluation of their inhibitory ability against LPO and DNA protective properties

Twelve 23-esterified silybin derivatives with different patterns of substituents such as aromatic and aliphatic groups （1-12） were designed and synthesized. The antioxidative properties of these compounds were evaluated. The modifed silybin analogues exhibited improved inhibitory effects against rat liver homogenate lipid peroxidation compared to silybin, with exception of the trimethoxylated ester （5） and the aliphatic one （9）. Compounds 3, 5, 7, 8 and 11 displayed their protective properties on DNA cleavage in a dose-dependent manner. 2009 Xiao Kun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Establishment and application of experimental model of human fetal hepatocytes: protective effects of silybin and polyporus umbellalus polysaccharides on human fetal hepatocytes

IM To establish a new experimental model system with human fetal hepatocytes to study the mechanisms of protective effect of silybin and polyporus umbellalus polysaccharides (PSP) on the ultrastructure of human fetal hepatocytes.METHODS The hepatocytes were obtained from the liver of human fetus from induced labor with written consent. The primarily cultured hepatocytes were pretreated with silybin and PSP and exposed to CCl4 for 4 hours. The ultrastructural changes of hepatocytes were observed under scanning electronmicroscopy (SEM) and transmission electronmicroscope (TEM). Transaminase and SOD were also assayed at the end of culture.RESULT The levels of ALT and AST were significantly decreased and the SOD level elevated in two pretreated groups as compared with that in the control group. The cellular integrity and ultrastructure of hepatocytes were well preserved in the two drugs pretreated groups while they were seriously damaged in the control group.CONCLUSION The experimental model system with human fetal hepatocytes pretreated with CCl4 could act as an effective method for studying the protective effect of drugs on human hepatocytes, and could be used for screening the medicines for treatment of hepatitis.

Curative effect of silybin combined with pituitrin-phentolamine for pulmonary tuberculosis complicated by acute hemoptysis

Objective: To study the curative effect of silybin combined with pituitrin-phentolamine for pulmonary tuberculosis complicated by acute hemoptysis. Methods: A total of 78 patients with pulmonary tuberculosis complicated by acute hemoptysis who were treated in this hospital between December 2013 and April 2017 were divided into control group (n=39) and silybin group (n=39) by random number table. Control group received pituitrin-phentolamine hemostasis therapy, silybin group received pituitrin-phentolamine combined with silybin therapy, both were treated for 1 week. The differences in peripheral blood liver function and coagulation index levels as well as serum oxidative stress index contents were compared between the two groups of patients before treatment and after 1 week of treatment. Results:Before treatment, the differences in peripheral blood liver function and coagulation index levels as well as serum oxidative stress index contents were not statistically significant between the two groups. After 1 week of treatment, peripheral blood liver function indexes ALT, AST, ALP and STB contents of silybin group were lower than those of control group;peripheral blood coagulation indexes PT, APTT and TT levels were lower than those of control group whereas Fib level was higher than that of control group;serum oxidative stress indexes AOPPs and LHP contents were lower than those of control group whereas GSH-Px and T-AOC contents were higher than those of control group. Conclusion: pituitrin-phentolamine combined with silybin therapy can effectively protect the liver function, optimize the coagulation function and reduce the oxidative stress response in patients with pulmonary tuberculosis complicated by acute hemoptysis.

In vitro and in vivo evaluation of a self-microemulsifying drug delivery system for silybin

To enhance the oral absorption of the poorly water-soluble drug silybin, a self-microemulsifying drug delivery system （SMEDDS） composed of ethyl linoleate, Cremophor EL and PEG 400 for oral administration of silybin was formulated, and its physicochemical properties and bioavailability of silybin were evaluated. The in vitro release of silybin from microemulsion and dispersion of silybin from SMEDDS were significantly faster than those from the commercial silybin hard capsule, respectively. The area under the drug concentration-time curve （AUC） and the mean maximum plasma level （Cmax） of the SMEDDS were remarkably greater than those of the hard capsule after oral administration to rats. The absorption of silybin formulated in SMEDDS exhibited a 2.3-fold increase in bioavailability as compared with the hard capsule. These results demonstrated that SMESDDS might be a useful drug delivery system for the oral delivery of the poorly water-soluble drug silybin.

柴胡疏肝散加减联合水飞蓟宾胶囊治疗慢性乙型肝炎合并非酒精性脂肪性肝病的疗效与安全性分析

目的分析柴胡疏肝散加减联合水飞蓟宾胶囊在慢性乙型肝炎合并非酒精性脂肪性肝病患者中的治疗效果。方法选取2019年6月—2023年6月徐州市传染病医院收治的116例慢性乙型肝炎合并非酒精性脂肪性肝病患者,按不同治疗方法分为两组,各58例。在常规抗病毒、保肝治疗的基础上,对照组口服水飞蓟宾胶囊治疗,观察组在此基础上增加柴胡疏肝散加减治疗。比较两组治疗总有效率、肝功能、血脂水平、体重指数及不良反应发生情况。结果观察组治疗总有效率为91.37%(53/58),高于对照组的74.14%(43/58),差异有统计学意义(χ^(2)=4.614,P<0.05)。治疗后,观察组患者的γ-谷氨酰转肽酶、天门冬氨酸氨基转移酶、丙氨酸氨基转移酶、低密度脂蛋白、甘油三酯、总胆固醇、体重指数低于对照组,高密度脂蛋白高于对照组,差异有统计学意义(P均<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论柴胡疏肝散加减联合水飞蓟宾胶囊治疗慢性乙型肝炎合并非酒精性脂肪性肝病可提升疗效,改善肝功能及血脂,且安全性高。

Preparation and evaluation of the solid dispersions of poorly soluble silybin

To improve its solubility and dissolution,solid dispersions of silybin in PVP K30 were prepared by the conventional solvent evaporation method and characterized by equilibrium solubility and dissolution studies,differential scanning calorimetry （DSC） and Fourier transform infrared spectroscopy（FTIR）.Silybin solid dispersions showed increased solubility and rates of dissolution compared with pure drug and corresponding physical mixtures of silybin and PVP K30.Thermograms of various solid dispersions did not show the melting peak of pure silybin,indicating that silybin was in amorphous form inside the polymer carrier.FTIR studies demonstrated the presence of interactions between hydroxyl groups of silybin and carbonyl groups of PVP K30 in solid dispersions.Solid dispersion techniques can be used to formulate water insoluble drugs to improve their dissolution in vitro and absorption in vivo.

观察肺结核患者采用水飞蓟宾胶囊预防抗结核药物肝损害的临床效果

目的 探讨对肺结核患者采用水飞蓟宾胶囊预防抗结核药物肝损害的临床效果。方法 100例肺结核患者作为研究对象,根据入院治疗时间顺序分为实验组和对照组,各50例。对照组通过常规的抗结核方式治疗,实验组以对照组为基准增加水飞蓟宾胶囊治疗。比较两组患者的肝功能指标[谷氨酰转肽酶(GGT)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)],不良反应发生情况,治疗效果,治疗满意度。结果 治疗后,实验组患者的ALT、AST、GGT、TBil水平显著低于治疗前,对照组患者的ALT、AST、GGT、TBil水平均高于治疗前,且实验组患者的ALT(34.65±6.23)U/L、AST(37.25±8.26)U/L、GGT(7.29±1.69)U/L、TBil(15.27±4.79)μmol/L均低于对照组的(44.76±7.15)U/L、(46.39±9.50)U/L、(12.47±3.01)U/L、(22.31±6.05)μmol/L,经统计学软件分析得出(P<0.05)。实验组不良反应发生率(14%)与对照组(18%)比较差异不大,经统计学软件分析得出(P>0.05)。治疗后,实验组总有效率(86%)高于对照组(68%),经统计学软件分析得出(P<0.05)。实验组治疗满意度(94%)高于对照组(76%),经统计学软件分析得出(P<0.05)。结论 水飞蓟宾胶囊对肺结核患者抗结核药物肝损害具有积极的预防作用,能减少不良反应的发生,可增强患者的治疗效果并提高患者的满意度,值得在临床上推广。

Simultaneous Determination of Silybin A and Silybin B in Rat Plasma and Pharmacokinetic Study

Objective To investigate the bioavailability and pharmacokinetics of silybin A and silybin B in rats,respectively. Methods Following iv and ig administration of silybin to 20 Wistar rats,the plasma samples were collected at different time points up to 12 h.Sample pretreatment was involved in one-step protein precipitation with acetonitrile. Silybin A and silybin B were simultaneously determined by LC-MS/MS.Results After ig dosing silybin 28,56,and 112 mg/kg to rats,the t1/2βvalues were 5.48,5.08,and 5.73 h for silybin A,and 4.56,4.12,and 5.53 h for silybin B; The Cmax were 674.3,1349.4,and 2042.5 ng/mL for silybin A,and 671.0,1365.4,and 2066.2 ng/mL for silybin B; The Tmax were 0.20,0.23,and 0.20 h for silybin A,and 0.20,0.23,and 0.20 h for silybin B;The AUC were 454.4, 845.9,and 1219.5 h·ng/mL for silybin A,and 432.0,817.1,and 1153.6 h·ng/mL for silybin B.The absolute bioavailabilities of silybin A and silybin B were 2.86%and 1.93%,respectively.Conclusion Silybin A and silybin B have very low bioavailability after ig administration,and there is no significant difference in the pharmacokinetic parameters between silybin A and silybin B,which indicates that the two diastereoisomers have similar pharmacokinetic behavior in rats.

Supersaturated polymeric micelles for oral silybin delivery: the role of the Soluplus–PVPVA complex

Increasing the degree of supersaturation of drugs and maintaining their proper stability are very important in improving the oral bioavailability of poorly soluble drugs by a supersaturated drug delivery system(SDDS). In this study, we reported a complex system of Soluplus–Copovidone(Soluplus–PVPVA)loaded with the model drug silybin(SLB) that could not only maintain the stability of a supersaturated solution but also effectively promote oral absorption. The antiprecipitation effect of the polymers on SLB was observed using the solvent-shift method. In addition, the effects of the polymers on absorption were detected by cellular uptake and transport experiments. The mechanisms by which the Soluplus–PVPVA complex promotes oral absorption were explored by dynamic light scattering, transmission electron microscopy, fluorescence spectra and isothermal titration calorimetry analyses. Furthermore, a pharmacokinetic study in rats was used to demonstrate the advantages of the Soluplus–PVPVA complex. The results showed that Soluplus and PVPVA spontaneously formed complexes in aqueous solution via the adsorption of PVPVA on the hydrophilichydrophobic interface of the Soluplus micelle, and the Soluplus–PVPVA complex significantly increased the absorption of SLB. In conclusion, the Soluplus–PVPVA complex is a potential SDDS for improving the bioavailability of hydrophobic drugs.

Silybin alleviates hepatic lipid accumulation in methionine-choline deficient diet-induced nonalcoholic fatty liver disease in mice via peroxisome proliferator-activated receptorα

Nonalcoholic fatty liver disease(NAFLD)is regarded as the most common liver disease with no approved therapeutic drug currently.Silymarin,an extract from the seeds of Silybum marianum,has been used for centuries for the treatment of various liver diseases.Although the hepatoprotective effect of silybin against NAFLD is widely accepted,the underlying mechanism and therapeutic target remain unclear.In this study,NAFLD mice caused by methionine-choline deficient(MCD)diet were orally administrated with silybin to explore the possible mechanism and target.To clarify the contribution of peroxisome proliferator-activated receptorα(PPARα),PPARαantagonist GW6471 was co-administrated with silybin to NAFLD mice.Since silybin was proven as a PPARαpartial agonist,the combined effect of silybin with PPARαagonist,fenofibrate,was then evaluated in NAFLD mice.Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARαand its targets.As expected,silybin significantly protected mice from MCD-induced NAFLD.Furthermore,silybin reduced lipid accumulation via activating PPARα,inducing the expression of liver cytosolic fatty acid-binding protein,carnitine palmitoyltransferase(Cpt)-1a,Cpt-2,medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1,and suppressing fatty acid synthase and acetyl-CoA carboxylaseα.GW6471 abolished the effect of silybin on PPARαsignal and hepatoprotective effect against NAFLD.Moreover,as a partial agonist for PPARα,silybin impaired the powerful lipid-lowering effect of fenofibrate when used together.Taken together,silybin protected mice against NAFLD via activating PPARαto diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARαagonists for NAFLD therapy.

水飞蓟宾抑制Fas/FasL信号通路对肺结核大鼠炎症损伤及巨噬细胞凋亡的影响

目的:探究水飞蓟宾对肺结核(TB)大鼠肺部炎症损伤、巨噬细胞凋亡的影响,及对死亡受体Fas及其配体FasL的调控作用。方法:采用尾静脉注射结核分枝杆菌(Mtb)法制备TB大鼠模型,并随机分为模型组、水飞蓟宾组、Fas过表达重组蛋白(pcDNA-Fas)组、pcDNA-Fas阴性对照(pcDNA-NC)组、水飞蓟宾+pcDNA-Fas组,每组15只,另取15只大鼠为正常对照组。抗酸染色检测肺组织感染情况;HE染色观察肺组织病理变化;ELISA法检测肺组织TNF-α、IL-6表达;Annexin VFITC/PI双染结合流式细胞术检测肺泡巨噬细胞凋亡率;Western blot检测Fas、FasL、caspase8、caspase3、巨噬细胞炎症蛋白-2(MIP-2)表达水平。结果:与正常对照组相比,模型组大鼠肺组织炎症因子表达、肺泡巨噬细胞凋亡率升高,肺组织Mtb感染及干酪样坏死严重,Fas/FasL介导的caspase8/3凋亡途径活化(P<0.05)。与模型组相比,水飞蓟宾组大鼠肺组织炎症因子表达、肺泡巨噬细胞凋亡率降低,肺组织Mtb感染及干酪样坏死缓解,Fas/FasL介导的caspase8/3凋亡途径活性降低(P<0.05)。pc-DNA-Fas可进一步激活Fas/FasL介导的caspase8/3凋亡途径活化,加重肺组织Mtb感染及干酪样坏死,促进肺组织炎症损伤及巨噬细胞凋亡,并减弱水飞蓟宾发挥的抗Fas/FasL活化、抗炎及抗巨噬细胞凋亡作用(P<0.05)。结论:水飞蓟宾可能通过抑制Fas/FasL信号通路发挥抗Mtb感染、抗肺组织巨噬细胞凋亡及抗肺部炎症损伤作用。

高效液相色谱法测定试验鸡肉中水飞蓟宾含量

为建立试验鸡肉中水飞蓟宾含量的高效液相色谱(high performance liquid chromatography,HPLC)检测方法,以乙酸乙酯为提取剂从鸡肉匀浆中提取水飞蓟宾后,采用C18色谱柱,在流动相为水∶甲醇=47∶53(体积比)、柱温30℃、流速0.65 mL/min、检测波长288 nm、进样量20μL的条件下进行分离检测。结果显示,水飞蓟宾标准品浓度在0.1~5.0μg/mL时线性关系良好,标准曲线方程为y=95.16x-0.8753,相关系数R2=0.9996,检测试验鸡肉中水飞蓟宾的平均回收率为88.45%~104.34%,相对标准偏差(relative standard deviation,RSD)为1.85%~2.94%。结果表明,该方法简单易行,精密度较高,回收率良好,可用于试验鸡肉中水飞蓟宾含量的测定。

水飞蓟宾对哮喘小鼠气道黏蛋白Muc5ac的影响及机制研究

目的观察水飞蓟宾对哮喘小鼠气道黏蛋白Muc5ac表达水平的影响,并探讨其可能作用机制。方法40只SPF级雌性BALB/c小鼠随机分为正常组(NS组)、哮喘组(AS组)、水飞蓟宾40 mg/kg组(Silybin40组)、水飞蓟宾80 mg/kg组(Silybin80组)、地塞米松组(DEX组)。通过OVA致敏和雾化激发制备哮喘小鼠模型。AS组、Silybin40组、Silybin80组及DEX组分别以PBS、水飞蓟宾40 mg/kg、水飞蓟宾80 mg/kg及地塞米松2 mg/kg干预。收集各组小鼠BALF,分别行细胞总数计数、嗜酸性粒细胞百分比,ELISA法检测IL-6及TNF-α水平;制备肺组织病理石蜡切片,行HE、AB-PAS观察肺组织病理学改变,IHC检测肺组织ERK、pERK、SP1、Muc5ac蛋白表达水平。结果AS组小鼠BALF细胞总数、嗜酸性粒细胞百分比、IL-6、TNF-α、气道周围炎症细胞浸润评分、气道黏液物质相对着色面积、肺组织pERK、SP1及Muc5ac蛋白水平均高于NS组(P<0.05),Silybin80组和Silybin40组BALF细胞总数、嗜酸性粒细胞百分比、IL-6、TNF-α、气道周围炎症细胞浸润评分、气道黏液物质相对着色面积、肺组织pERK、SP1及Muc5ac蛋白水平均低于AS组(P<0.05),且Silybin80组上述指标的水平均低于Silybin40组。结论水飞蓟宾干预可抑制哮喘小鼠气道炎症和气道黏液高分泌,其机制可能与抑制ERK/SP1信号通路有关。

水飞蓟素衍生物抗肝损伤作用的实验研究

目的:观察水飞蓟素衍生物抗肝损伤作用并探讨其作用机制。方法:48只小鼠随机分为6组,即正常组,模型组,水飞蓟素衍生物低剂量(25 mg/kg)、中剂量(50 mg/kg)、高剂量(100 mg/kg)组及水飞蓟宾对照组(100 mg/kg),连续灌胃给药5 d。于末次给药1 h后,除正常组外其余各组小鼠腹腔注射给予对乙酰氨基酚(350 mg/kg)进行造模,禁食不禁水,24 h后腹腔静脉取血和肝组织,检测各组小鼠血清学丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和肝组织丙二醛(MDA)、谷胱甘肽(GSH)以及谷氨酸脱氢酶(GDH)含量,HE染色观察肝组织病理变化。结果:各剂量衍生物能够降低对乙酰氨基酚诱导的肝损伤小鼠血清学ALT、AST指标以及肝组织MDA、GDH水平,并升高GSH含量;同时能够不同程度改善对乙酰氨基酚对肝组织的损伤,展现出不同程度的抗肝损伤活性。结论:水飞蓟素衍生物能够通过调节肝组织MDA、GDH、GSH等指标发挥抗小鼠肝损伤作用。

替诺福韦联合水飞蓟宾治疗乙肝肝硬化的临床研究

目的分析替诺福韦联合水飞蓟宾治疗乙型肝炎(乙肝)肝硬化的临床效果。方法选出86例乙肝肝硬化患者,依照不同用药方案分成A组(43例)与B组(43例)。A组采用替诺福韦治疗,B组采用替诺福韦联合水飞蓟宾治疗。比较两组肝功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)]、肝纤维化指标[Ⅳ型胶原(CⅣ)、Ⅲ型前胶原肽氨基末端肽(PⅢNP)、层粘连蛋白(LN)、透明质酸(HA)]、Child-Pugh评分、临床疗效、不良反应发生情况。结果B组用药后的ALT、AST、TBIL分别为(36.57±6.57)U/L、(30.93±4.87)U/L、(20.66±2.30)μmol/L,均低于A组的(50.12±7.20)U/L、(42.76±5.53)U/L、(29.83±2.89)μmol/L(P<0.05)。B组用药后的CⅣ、PⅢNP、LN、HA分别为(65.77±20.53)、(115.93±34.51)、(85.61±24.28)、(104.93±32.15)μg/L,低于A组的(92.52±27.28)、(143.76±45.40)、(107.54±32.73)、(152.34±41.72)μg/L(P<0.05)。A组用药前的Child-Pugh评分为(8.66±1.54)分,用药后为(6.92±1.36)分;B组用药前的Child-Pugh评分为(8.70±1.51)分,用药后为(5.73±1.10)分。两组用药前Child-Pugh评分无差异(P>0.05);B组用药后的Child-Pugh评分低于A组(P<0.05)。A组总有效率为79.07%(34/43),B组总有效率为95.35%(41/43);B组的总有效率高于A组(P<0.05)。两组的不良反应总发生率相近(P>0.05)。结论替诺福韦联合水飞蓟宾治疗乙肝肝硬化的效果较好,可以显著改善患者的肝功能指标与肝纤维化指标,有助于患者病情的良好控制,总有效率高,且与单纯采用替诺福韦治疗相比不增加不良反应,有效性与安全性均较好,可采纳、推行。

恩替卡韦联合水飞蓟宾治疗乙肝合并非酒精性脂肪肝患者的临床疗效及对患者肝功能的影响

【目的】探讨恩替卡韦联合水飞蓟宾治疗乙型病毒性肝炎(CHB)合并非酒精性脂肪肝(NAFLD)患者的临床疗效及对患者肝功能的影响。【方法】选取2021年6月至2023年1月本院收治的104例CHB合并NAFLD患者,根据治疗方法将其分为对照组(在常规治疗的基础上给予恩替卡韦治疗)和观察组(在对照组的基础上给予水飞蓟宾治疗),每组52例。比较两组临床效果、肝功能[丙转氨酶(ALT)、谷草转氨酶(AST)、肿瘤标志物甲胎蛋白(AFP)]、肝纤维化指标[层粘连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(Ⅳ-C)、透明质酸(HA)]、炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)]。【结果】观察组总有效率高于对照组,差异有统计学意义(P<0.05)。治疗后,两组ALT、AST、AFP低于治疗前,且观察组低于对照组(P<0.05);两组血清LN、PC-Ⅲ、Ⅳ-C、HA水平低于治疗前,且观察组低于对照组(P<0.05);两组血清IL-6、TNF-α、NF-κB水平低于治疗前,且观察组低于对照组(P<0.05)。【结论】恩替卡韦联合水飞蓟宾治疗CHB合并NAFLD患者可改善肝功能,减轻机体炎症反应,缓解肝纤维化进展。

水飞蓟宾治疗乳腺癌研究进展

乳腺癌发病率高,严重威胁女性健康,寻找治疗乳腺癌的药物至关重要。为给水飞蓟宾在乳腺癌临床治疗中的进一步应用提供理论基础,研究综述了水飞蓟宾在乳腺癌细胞中的作用机制:水飞蓟宾能阻滞乳腺癌细胞周期;能通过线粒体途径有效抑制乳腺癌细胞的侵袭和迁移,诱导癌细胞的自噬和凋亡;能多途径调节肿瘤微环境,抑制肿瘤血管生成,抑制乳腺癌细胞的增殖并诱导凋亡;具有强大的抗转移活性,可与其他天然药物联用发挥协同抗癌作用。