汉黄芩素抗肿瘤和免疫调节作用的研究进展

汉黄芩素是一种天然黄酮类化合物。最近研究发现,汉黄芩素具有广泛的抗肿瘤作用,其作用显示出多途径、多环节、多靶点的特点;如可通过ROS途径和Ca²⁺介导的信号通路促进肿瘤细胞的凋亡、增强TNF-α和TRAIL对肿瘤细胞的毒性、阻滞肿瘤细胞的细胞周期、抑制肿瘤血管生成、协同化疗药物抗癌活性等。另外,汉黄芩素可通过增加免疫细胞的浸润、调节免疫细胞的表型、以及促进相关细胞因子的分泌来增强免疫功能。该文就汉黄芩素抗肿瘤和免疫增强活性的研究进展进行了综述。     

汉黄芩素的提取及抗肿瘤的作用机制

汉黄芩素是中药黄芩中一种黄酮类化合物,最新研究发现汉黄芩素能抑制肿瘤细胞增殖,通过影响肿瘤细胞形态以及下调Bax/Bcl-2增加肿瘤细胞凋亡,阻滞细胞周期、抑制端粒酶活性以促进肿瘤细胞死亡,并且能够抑制肿瘤细胞转移。文章就国内对汉黄芩素的提取、汉黄芩素以上几方面的抗肿瘤作用的研究进展作一综述。     

黄芩黄酮类成分抗肿瘤作用及机制研究进展

黄芩黄酮类成分具有广泛的抗肿瘤活性,药理研究证实通过调节花生四烯酸系统的代谢,抑制肿瘤细胞增殖,诱导细胞凋亡,抑制新生血管生成等作用途径发挥抗肿瘤作用。通过对黄芩黄酮类成分抗肿瘤作用及其机制的文献总结,为中药活性成分的研究提供一定的理论基础。     

酶法提取黄芩中黄芩素、汉黄芩素

目的:研究纤维素酶法提取黄芩中黄芩素、汉黄芩素的最佳工艺条件。方法:采用HPLC法测定黄芩素、汉黄芩素含量,以提取率为指标,分别考察浸提倍数、加酶量、pH、温度、时间对纤维素酶解反应的影响。结果:实验确定了纤维素酶解黄芩药材的最佳工艺条件:浸提倍数20,加酶量20 U/g药材,pH 4.8,温度50℃,时间8 h。结论:与传统水煎提取工艺相比,酶法提取工艺提取使得黄芩中黄芩素提取率提高了5倍、汉黄芩素提取率提高了近4倍。     

汉黄芩素体外抗人胃癌SGC7901细胞的增殖、凋亡作用

 目的 探讨汉黄芩素对人胃癌SGC7901细胞增殖抑制和凋亡诱导作用。方法 应用四甲基偶氮唑盐（MTT法测定汉黄芩素对于SGC7901细胞增殖活性;应用肿瘤细胞侵袭实验观察细胞侵袭能力;应用形态学方法、流式细胞仪测定汉黄芩素对SGC7901细胞的凋亡作用,进行细胞周期分析,并观察对胃癌细胞内活性氧（ROS的影响。结果 汉黄芩素对SGC7901细胞增殖和侵袭活性具有明显抑制作用,其抑制细胞增殖的IC₅₀为（74.26±1.21μmol·L-1,汉黄芩素也具有诱导胃癌细胞凋亡作用,荧光染色可见明显核碎裂、染色体聚集,并使胃癌细胞阻滞于G₀/G₁期;使肿瘤细胞内ROS水平明显升高。结论 汉黄芩素对胃癌SGC7901细胞的增殖有抑制及促进凋亡的作用,可能与上调细胞内ROS水平有关。     

UPLC同时测定黄芩中黄芩苷、黄芩素、汉黄芩苷、汉黄芩素、千层纸素A

目的 建立用超高效液相色谱（UPLC）同时测定黄芩中黄芩苷、黄芩素、汉黄芩苷、汉黄芩素、千层纸素A 5种成分的方法。方法 采用UPLC色谱系统,BEH C₁₈色谱柱（50 mm×2.1 mm,1.7 μm）;流动相为乙腈-0.1%甲酸,梯度洗脱,体积流量为0.6 mL/min;进样量为2 μL;检测波长为280 nm。结果 本方法可在15 min内完成1次色谱分析,黄芩苷、黄芩素、汉黄芩苷、汉黄芩素、千层纸素A色谱峰之间有良好的分离度,5种成分的浓度和各自峰面积之间有着良好的线性关系,精密度、重复性及加样回收率的RSD均小于3.0%。结论 本方法快捷、准确,重复性好,能同时测定黄芩中黄芩苷、黄芩素、汉黄芩苷、汉黄芩素、千层纸素A 5种成分的量。     

HPLC同时测定糖痹康颗粒中黄芩苷、汉黄芩苷、黄芩素、汉黄芩素的含量

目的建立同时测定糖痹康颗粒中黄芩苷、汉黄芩苷、黄芩素、汉黄芩素含量的方法。方法采用高效液相色谱法。色谱柱:Thermo syncronis C18(250 mm×4.6 mm,5μm);流动相:0.1%甲酸乙腈(A)-0.1%甲酸水(B);梯度洗脱:0~3 5 m i n,2 0%(B)~5 5%(B);3 5~4 0 m i n,1 0 0%(B);流速:1 m L/min;柱温为40℃;检测波长为275 nm;进样量为20μL。结果黄芩苷检测浓度在5~500μg/m L范围内与峰面积积分值呈良好线性关系Y=6×107X+62726(r=0.9996,n=7);平均回收率为100.06%,RSD=1.08%(n=9);汉黄芩苷检测浓度在1~85μg/m L范围内与峰面积积分值呈良好线性关系Y=90214X-51875(r=0.9997,n=7);平均回收率为100.11%,RSD=0.41%(n=9);黄芩素检测浓度在0.4~25μg/m L范围内与峰面积积分值呈良好线性关系Y=158201X-10020(r=0.9997,n=7);平均回收率100.00%,RSD=0.73%(n=9);汉黄芩素检测浓度在0.1~10μg/m L范围内与峰面积积分值呈良好线性关系Y=69606X-29918(r=0.9991,n=7);平均回收率为100.07%,RSD=1.17%(n=9);结论该方法操作简单,结果可靠,可为糖痹康颗粒的质量控制提供参考。     

汉黄芩素抑制乳腺癌细胞增殖及侵袭的实验研究

目的：研究汉黄芩素对乳腺癌细胞MDA-MB-231生长和增殖的影响,同时观察汉黄芩素对MDA-MB-231细胞黏附、迁移和侵袭能力的影响,进一步探讨其分子作用机制。方法：MTT法检测汉黄芩素对MDA-MB-231细胞生长的影响;Ki-67法检测汉黄芩素对细胞增殖的影响;划痕实验、黏附试验和侵袭小室法检测对MDA-MB-231细胞迁移和侵袭能力的影响;Western blotting检测对增殖和转移相关蛋白及相关信号通路的影响。结果：汉黄芩素能明显抑制MDA-MB-231细胞生长和增殖;低浓度情况下明显抑制乳腺癌细胞的迁移、黏附和侵袭能力;汉黄芩素有效抑制MDA-MB-231细胞Survivin,Bcl-2,ICAM-1,MMP-2,MMP-9蛋白的表达。结论：汉黄芩素明显抑制乳腺癌细胞生长和增殖,并抑制MDA-MB-231细胞迁移、黏附、侵袭,其对MDA-MB-231细胞的侵袭和黏附影响可能与其降低ICAM-1,MMP-2,MMP-9表达有关。     

HPLC法测定清肝散结颗粒中黄芩苷、汉黄芩苷、野黄芩苷、黄芩素及汉黄芩素

目的对清肝散结颗粒(猫人参、石见穿、白花蛇舌草、半枝莲及黄芩等)中所含的黄酮类化学成分黄芩苷、汉黄芩苷、野黄芩苷、黄芩素及汉黄芩素同时进行测定,建立制剂质量控制方法。方法采用高效液相色谱法,Waters Xterra Rp-C18色谱柱(3.0 mm×100 mm,3.5μm),流动相为乙腈(A)与0.1%甲酸水溶液(B),梯度洗脱,体积流量0.4 mL/min,柱温20℃,紫外检测波长为275 nm,进样量5μL,运行时间60 min。结果 5个待测化合物与周围干扰峰达到基线分离,线性范围分别为黄芩苷4.604⁴60.4μg/mL(r=0.999 9);汉黄芩苷0.770 4460.4μg/mL(r=0.999 9);汉黄芩苷0.770 4⁷7.04μg/mL(r=0.999 6);野黄芩苷0.415 777.04μg/mL(r=0.999 6);野黄芩苷0.415 7⁴1.57μg/mL(r=0.999 8);黄芩素0.845 641.57μg/mL(r=0.999 8);黄芩素0.845 6⁸4.56μg/mL(r=0.999 9);汉黄芩素0.799 284.56μg/mL(r=0.999 9);汉黄芩素0.799 2⁷9.92μg/mL(r=0.999 7),日内/日间精密度均小于3%(n=3),平均回收率在97%79.92μg/mL(r=0.999 7),日内/日间精密度均小于3%(n=3),平均回收率在97%¹02%之间(n=6)。清肝散结颗粒中黄芩苷、汉黄芩苷、野黄芩苷、黄芩素及汉黄芩素的含有量分别为3.798、0.829 9、0.180 5、0.158 9、0.0726 mg/g。结论该法简便、快捷、结果准确、重复性好、实用性强,可用于清肝散结颗粒中的质量控制。     

中药单体汉黄芩素诱导肺癌细胞凋亡及其机制初步研究

目的 考察汉黄芩素对肺癌细胞株A549的增殖、凋亡的影响,并初步探讨其分子机制.方法 MTT法检测汉黄芩素对A549增殖的影响;Hochest染色、流式细胞仪等检测对细胞凋亡的影响;Western-blotting检测汉黄芩素对凋亡相关蛋白的影响.结果 汉黄芩素能抑制A549细胞的生长,其细胞增殖抑制率与药物浓度及作用时间呈依赖关系.形态学上观察汉黄芩素明显诱导肺癌细胞A549凋亡,同时明显抑制了凋亡相关蛋白BCL-2、survivin蛋白的表达,提升Bax蛋白表达.结论 汉黄芩素可以明显诱导肺癌细胞A549的凋亡,其诱导凋亡分子机制可能与下调BCL-2、survivin蛋白表达有关.     

茯苓多糖的免疫效应和抗肿瘤作用研究进展

茯苓多糖抗肿瘤机制具有多靶点,多层次,多途径的优势,临床的开发和应用具有广阔的前景;茯苓多糖不但具有提高机体免疫监视清除功能,增强机体对肿瘤细胞的杀伤能力,还可以打破机体免疫耐受,逆转肿瘤细胞免疫逃逸,增强机体的抗肿瘤免疫效能;现对近几年的国内外关于茯苓多糖免疫效应和抗肿瘤方面的研究进行综述,深入研究其药理作用,为其成为临床抗肿瘤新药奠定理论基础。     

Gene expression profiling reveals the plausible mechanisms underlying the antitumor and antimetastasis effects of Andrographis paniculata in esophageal cancer

Esophageal cancer (EC) is a seriously invasive malignancy with high mortality and poor prognosis. Metastasis of EC is the major cause of mortality. Our studies previously demonstrated that a herbal medicine Andrographis paniculata (AP) significantly suppressed EC growth and metastasis in vitro and in vivo. However, the underlying mechanisms responsible for these effects have not yet been systematically elucidated. In this context, gene expression profiling of AP‐treated squamous EC cells (EC‐109) was performed to reveal the regulatory mechanisms of AP in antitumor and antimetastasis signaling pathways using gene expression microarray analysis. Differentially expressed genes were identified by Affymetrix Gene Chip, followed by the real‐time polymerase chain reaction validation. The results showed that the canonical pathways were significantly regulated by AP treatment, including multiple genes related to proliferation, apoptosis, intercellular adhesion, metastatic processes, and drug resistance, such as WNT, TGF‐β, MAPK and ErbB signaling pathways, and ATP‐binding cassette transporter subfamily members. This genomic study emerges candidate molecular targets and pathways to reveal the mechanisms involved in AP's effects, which provides scientific evidence to support the clinical application of AP in EC treatment.     

四君子汤与环磷酰胺合用对荷瘤小鼠免疫功能的影响及抑瘤作用

用缸细胞c抽花环和免疫台物花环形成试验观察了四君于汤与环磷酰胺台用对sm荷瘤小鼠红细胞免疫功能的影响及抑瘤作用。结果显示：四君于两能增强小鼠虹细胞Cn花环形成率和血清中红细胞免疫粘附促进因子水平，降低免疫复合特花环形成率以荻免疫粘附抑帝制因子的水平，并能拮抗环辟酰胺的免疫抑制作用，增强环磷酰胺的抑瘤效应。     

桑黄抗肿瘤及其作用机制的研究进展

桑黄(phellinus)作为一种名贵的真菌类药材,具有抗肿瘤、抗肝纤维化、抗氧化等多种生理功能。桑黄含有多糖类、甾体类、萜类、黄酮类、吡喃酮类、呋喃类、生物碱类等物质。其中多糖类提取物具有明显抗肿瘤作用,成为当前抗癌药物研究的热点;桑黄的其他提取物如乙酸乙酯提取物等也表现出抗癌活性。该文综述桑黄不同提取物的抗肿瘤作用,着重介绍其抗肿瘤机制的研究进展,为进一步开发桑黄奠定基础。     

Orally administered mycelial culture of Phellinus linteus exhibits antitumor effects in hepatoma cell-bearing mice

Aim of the study

The aim of this study was to evaluate the anticancer effect of a mycelial culture from Phellinus linteus PL-7 (MCPL-7) and to elucidate its potential mechanism in vivo.

Materials and methods

SCID CB-17 mice received a transplant of Hep3B cells followed by daily MCPL-7 administrations for 8 weeks. Following tumor implantation, groups C-E were subcutaneously administered 50 mg/kg, 100 mg/kg, or 250 mg/kg MCPL-7 powder per day, respectively, for 8 weeks. Groups A and B received saline solution subcutaneously for 8 weeks.

Results

MCPL-7 administration induced a significant reduction in tumor size and was associated with a significant increase in T cell numbers; IL-12, IFN-γ and TNF-α secretion; NK cell activity; and phagocytic ability. Therefore, increased numbers of CD4⁺cells could have been caused by greater numbers of dendritic cells and macrophages in the spleen. Furthermore, the activation of dendritic cells and macrophages resulted in increased IL-12 secretion, which could upregulate NK cell activation. The increased secretion of IL-12, IFN-γ, and TNF-α enhanced the activity and phagocytic ability of NK cells. Thus, MCPL-7 may provide a potential therapeutic approach for both immunomodulatory and antitumor effects.     

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest, apoptosis and autophagy, as well as suppressed tumor cell proliferation, obstructed angiogenesis and metastasis, enhanced immunity, and reversal of multidrug resistance. The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.     

中医药治疗银屑病的相关分子机制研究进展

银屑病是常见的难治性皮肤科疾病,对患者身心健康带来极大的影响。中医药治疗银屑病具有疗效好,副作用低的作用特点。文章就近年来中医药临床治疗银屑病所涉及的分子作用机制进行总结,分别从中医药对银屑病患者表皮细胞作用的分子机制、对免疫系统的细胞及分子作用的影响、对血循环及血流变的影响、对黏附分子、金属蛋白酶及其他分子表达的影响等方面进行综述。     

吴茱萸生物碱抗肿瘤活性的研究

目的:研究吴茱萸生物碱的抗肿瘤活性.方法:取从吴茱萸中分离得到的吴茱萸碱粗品,以吴茱萸碱粗品500mg/kg灌胃给予大鼠,考察吸收入血成分;通过离体抗肿瘤活性实验,考察对MCF-7、HL-60、K562、SPC-A-1和NCI-H446等5种肿瘤细胞的影响;通过在体抗肿瘤活性实验,考察吴茱萸碱对小鼠S180、HepA和MFC的影响.结果:大鼠口服吴茱萸碱粗品后吸收入血的主要成分为吴茱萸碱.离体实验发现吴茱萸碱粗品对MCF-7、SPC-A-1、NCI-H446等肿瘤细胞有明显抑制作用;在体实验发现吴茱萸碱粗品对S180、MFC、HepA等小鼠肿瘤细胞有明显抑制作用.结论:吴茱萸生物碱具有很强的抗肿瘤活性.     

Cardioprotective effects and underlying mechanisms of oxymatrine against Ischemic myocardial injuries of rats

Oxymatrine has been demonstrated to have a variety of pharmacological actions. Accumulating evidence indicates that oxymatrine may exert a protective effect on the cardiovascular system. The study was designed to explore the possible role of oxymatrine against myocardial ischemic damage and several related signaling pathways as potential mechanisms. The protective properties of oxymatrine were studied in a rat model of acute myocardial infarction due to permanent ligation of the left anterior descending coronary artery. The results showed that administration of oxymatrine relieved myocardial injuries during ischemia, and this was achieved by protecting cardiomyocytes from apoptotic death. The beneficial effects of oxymatrine were likely mediated by an inhibition of lipid peroxidation (MDA production) and an increase in endogenous antioxidant activity (SOD), activation of the survival signaling molecule (Bcl-2), and a reduction of apoptotic mediator (Fas) and intracellular Ca2+ overload.