黄芩素抗肿瘤作用机制的研究进展

黄芩素是传统中药黄芩的主要有效成分,近年来国内外研究表明,黄芩素可抑制多种肿瘤细胞增殖,特异性地诱导肿瘤细胞凋亡,阻滞肿瘤细胞周期,抑制端粒酶活性及肿瘤血管生成、侵袭、转移等。本研究对黄芩素的抗肿瘤研究现状及以上几方面的作用机制进行综述,为其在抗肿瘤方面的临床应用提供理论基础。     

黄芩素的抗肿瘤作用及机制的研究进展

黄芩作为清热类中药广泛应用于临床,近年来国内外研究表明,黄芩中黄酮成分黄芩素,通过调节花生四烯酸系统的代谢,诱导肿瘤细胞周期停滞,诱导肿瘤细胞凋亡,抑制肿瘤新生血管生成,抗肿瘤侵袭和转移,增强肿瘤细胞对化疗药物的敏感性等机制发挥其抗肿瘤作用。本文对黄芩素抗肿瘤作用的研究现状及机制作一综述,为临床的进一步应用提供理论基础。     

黄芩素抗乳腺癌机制的研究现状及最新进展

乳腺癌临床上一般采用手术切除治疗,术后放疗和化疗普遍存在着各种严重的不良反应,因此从天然物质中寻找安全有效、不良反应小的抗癌药物成为了近年来医学界研究的热点课题。近年来使用中药治疗肿瘤已经引起了人们的高度关注和重视,黄芩素作为中药的有效成分,其具有广泛的药理作用和生物学活性,近年来关于黄芩素的抗肿瘤作用机制研究越来越多,大量的体内外实验都证实黄芩素具有抑制肿瘤血管新生、诱导细胞凋亡以及抑制肿瘤细胞增殖的作用。本文就黄芩素抗乳腺癌机制的研究现状及最新进展进行探析。     

黄芩素和黄芩苷的药理作用及机制研究进展

黄芩在我国药用历史悠久,黄芩素和黄芩苷是黄芩发挥功效的主要活性成分。黄芩素和黄芩苷具有抗菌抗病毒、清除氧自由基、抗氧化、解热、镇痛、抗炎、抗肿瘤、保护心脑血管及神经元、保肝、预防或治疗糖尿病及其并发症等作用,本文对黄芩素和黄芩苷的药理作用及作用机制的研究进展进行综述。     

汉黄芩素与氟尿嘧啶联用抗人肝癌细胞Hep-G2作用的拮抗效应研究

目的 探讨汉黄芩素(wogonin)联合氟尿嘧啶(5-FU)对人肝癌细胞Hep-G2生长活性的影响。 方法 实验分汉黄芩素组、5-FU组、汉黄芩素+5-FU组和空白对照组,采用MTT法观察药物对肿瘤细胞体外生长活性的影响,采用流式细胞仪分析肿瘤细胞凋亡率的变化。 结果 MTT实验结果显示汉黄芩素(5、10、20、40 μmol/L)作用24、48 h后对肿瘤细胞具有一定的增殖抑制作用(P<0.05);5-FU(5、10、20、40 mg/L)作用24、48 h后对肿瘤细胞增殖有明显的抑制作用(P<0.05);与单用组对肿瘤细胞的抑制作用相比,汉黄芩素联合5-FU组的抗肿瘤作用呈相互拮抗作用(P<0.05);汉黄芩素联合5-FU给药48 h后,联合指数CI值呈现剂量依赖性,CI值随汉黄芩素浓度的加大而增大,说明随汉黄芩素浓度的加大,其拮抗5-FU抗肿瘤效应的作用也越来越明显(P<0.05)。 结论 汉黄芩素具有一定的抗肿瘤作用,但可拮抗5-FU的抗肿瘤作用,具体机制有待进一步研究。     

黄芩素的制备及抗肿瘤药理作用研究进展

目的：黄芩是我国传统的中草药,黄芩中的活性成分具有广泛的药理作用,近年来对其药理作用尤其抗肿瘤的研究成为热点。本文综述近年黄芩的活性成分黄芩素的提取分离及抗肿瘤的药理作用。     

黄芩素对糖尿病周围神经病变保护作用机制研究进展

糖尿病周围神经病变(DPN)是糖尿病最常见的慢性并发症之一,也是糖尿病患者致残、致死的主要原因。黄芩素具有抗炎、抗变态反应、抗氧化应激、抗肿瘤、抗菌、抗血栓形成和保护肝、心脑血管、神经元等多种生物学作用。黄芩素对糖尿病周围神经病变有一定的防治作用,本文对黄芩素防治糖尿病周围神经病变的作用机制作一综述。     

黄芩及其有效成分的药理学研究进展

综述了黄芩及其有效成分黄芩苷、黄芩苷元、汉黄芩素、汉黄芩苷、黄芩新素Ⅰ和黄芩新素Ⅱ等黄酮类化合物的抗氧化、抗炎、抗变态、抗菌、抗病毒以及抗肿瘤等药理作用。     

黄芩素的药理学研究进展

黄芩素（黄芩苷元，Baicalein BAI）是从唇形科植物黄芩的干燥根中提取的有效成份之一，具有多种药理作用，如：抗菌、抗病毒、抗炎、抗变态反应、抗氧化、清除氧自由基、抗癌、抗肿瘤、抗凝、抗血栓形成和保护肝脏、心脑血管、神经元等作用。目前临床主要用于抗炎和抗菌。现概述国内外对黄芩素的药理作用及可能的作用机制的研究进展，为黄芩素的开发和更广泛地应用于临床提供依据。     

天然产物汉黄芩素的研究进展

天然产物汉黄芩素(wogonin)具有广泛的生物活性,如抗氧化、抗炎、神经保护、抗肿瘤和抗病毒活性等,目前引起了国内外学者的广泛关注。本文综述了近年来国内外关于汉黄芩素的植物提取、人工合成、生物活性及其作用机制方面的研究进展。     

黄芩素对肝癌H22荷瘤小鼠的抑瘤作用研究

目的:研究黄芩素对肝癌H22荷瘤小鼠的抑瘤作用。方法:以H22肝癌细胞接种于正常小鼠左前肢腋窝皮下复制肝癌H22荷瘤模型。实验分为模型对照、环磷酰胺(30mg·kg-1)和黄芩素高、中、低剂量(80、40、20mg·kg-1)组。灌胃给药,每天1次,连续15d。末次给药后处死小鼠,剥离完整的肿瘤组织称重,并计算肿瘤抑制率;流式细胞仪分析细胞周期分布和凋亡率;按试剂盒说明书测定肿瘤组织中半胱氨酸蛋白酶(Caspase)-3的活性;RT-PCR测定瘤组织中B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的mRNA表达水平。结果:高、中剂量黄芩素可显著抑制模型小鼠体内肿瘤生长(P<0.01或P<0.05),抑制率分别为61.63%和44.65%;可显著提高G0/G1期细胞百分比(P<0.05),并减少S期细胞(P<0.01或P<0.05)。与模型对照组比较,黄芩素高、中、低剂量组细胞凋亡率显著提高(P<0.01或P<0.05)。高、中剂量黄芩素可显著增强肿瘤组织中Capcase-3活性(P<0.01或P<0.05),抑制Bcl-2mRNA表达(P<0.01或P<0.05);高剂量黄芩素可显著提高肿瘤组织中BaxmRNA表达(P<0.05)。结论:黄芩素可促进肝癌H22荷瘤小鼠肿瘤细胞的凋亡,其机制可能与增强Capcase-3活性、提高Bax表达,并抑制Bcl-2表达有关。     

Biological properties of baicalein in cardiovascular system

The dried roots of Scutellaria baicalensis (S. baicalensis) Georgi (common name: Huangqin in China) have been widely employed for many centuries in traditional Chinese herbal medicine as popular antibacterial and antiviral agents. They are effective against staphylococci, cholera, dysentery, pneumococci and influenza virus. Baicalein, one of the major flavonoids contained in the dried roots, possesses a multitude of pharmacological activities. The glycoside of baicalein, baicalin is a potent anti-inflammatory and anti-tumor agent. This review describes the biological properties of baicalein (Table 1), which are associated with the prevention and treatment of cardiovascular diseases. Baicalein is a potent free radical scavenger and xanthine oxidase inhibitor, thus improving endothelial function and conferring cardiovascular protective actions against oxidative stress-induced cell injury. Baicalein lowers blood pressure in renin-dependent hypertension and the in vivo hypotensive effect may be partly attributed to its inhibition of lipoxygenase, resulting in reduced biosynthesis and release of arachidonic acid-derived vasoconstrictor products. On the other hand, baicalein enhances vasoconstricting sensitivity to receptor-dependent agonists such as noradrenaline, phenylephrine, serotonin, U46619 and vasopressin in isolated rat arteries. The in vitro effect is likely caused by inhibition of an endothelial nitric oxide-dependent mechanism. The anti-thrombotic, anti-proliferative and anti-mitogenic effects of the roots of S. baicalensis and baicalein are also reported. Baicalein inhibits thrombin-induced production of plasminogen activator inhibitor-1, and interleukin-1beta- and tumor necrosis factor-alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells. The pharmacological findings have highlighted the therapeutic potentials of using plant-derived baicalein and its analogs for the treatment of arteriosclerosis and hypertension.     

Baicalein, a flavonoid extracted from a methanolic extract of Oroxylum indicum inhibits proliferation of a cancer cell line in vitro via induction of apoptosis

A methanolic extract of the fruits of Oroxylum indicum, which is widely used in traditional Chinese herbal medicine for its anti-inflammatory, anti-pyretic and anti-hypersensitivity effects, inhibited in vitro proliferation of HL-60 cells. The flavonoid baicalein was found as an active component in the extract. Analysis of freeze-dried fruits of the plant indicated that this component comprised about 4% of the material by dry weight. In this study, we investigated the in vitro effects of baicalein on the viability and induction of apoptosis in the HL-60 cell line. The cell viability after treating with baicalein for 24 h was quantified by counting viable cells using trypan blue staining. The results showed that baicalein caused a 50% inhibition of HL-60 cells at concentrations of 25-30 microM. The inhibition of proliferation of HL-60 cells due to 36-48 h exposure to 10 or 20 microM baicalein was associated with the accumulation of cells at S or G2M phases. However, proliferation inhibition at a higher dose may be associated with induction by apoptosis, as evidenced by the typical nuclear fragmentation using DNA fragmentation assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The results indicate that baicalein has anti-tumor effects on human cancer cells, and Oroxylum indicum extract could be used in supplementary cancer therapy.     

Effects of baicalein on apoptosis,cell cycle arrest,migration and invasion of osteosarcoma cells

Baicalein is a bioactive flavonoid that is widely used in ancient China. However, its effects on the most common primary malignant bone tumor, osteosarcoma, remain unknown. In the present study, we investigated the effects of baicalein in osteosarcoma cells. Our results indicate baicalein might be an efficacious anti-osteosarcoma drug. We found that baicalein could inhibit cell proliferation in a time- and dose-dependent manner. Additionally, we demonstrated that baicalein promotes osteosarcoma cell apoptosis, and our mechanistic studies suggest that this is mediated by caspase activation, especially caspase-3. We also showed that the down-regulation of Bcl-2 and concurrent increase in Bax and Bim levels contribute to the apoptosis induced by baicalein. In addition, we observed that baicalein induces G1 cell cycle arrest by decreasing cyclin D1 and cyclin-dependent kinase 4 (CDK4). Furthermore, our data verifies that baicalein can reduce osteosarcoma cell adhesion, migration and invasion in vitro, which indicates its potential to inhibit osteosarcoma metastasis. The decrease in expression of matrix metalloproteinases (MMP)-2 and MMP-9 may contribute to the effects of baicalein. Taken together, our results provide evidence that baicalein plays important roles in anti-osteosarcoma therapy, and thus may serve as a novel and efficient candidate agent for osteosarcoma treatment.     

A tumor-targeting cRGD-EGFR siRNA conjugate and its anti-tumor effect on glioblastoma in vitro and in vivo

The epidermal growth factor receptor (EGFR) is an important anti-tumor target. The development of novel molecular-targeted anti-tumor drugs that can target the interior of tumor cells and specifically silence EGFR expression is valuable and promising. In this work, a promising anti-tumor conjugate comprising methoxy-modified EGFR siRNA and cyclic arginine-glycine-aspartic acid (cRGD) peptides, which selectively bind to αvβ3 integrins, was synthesized and examined. To prepare cRGD-EGFR siRNA (cRGD-siEGFR), cRGD was covalently conjugated to the 5′-end of an siRNA sense strand using a thiol-maleimide linker. The cellular uptake and cytotoxicity of cRGD-siEGFR in vitro were tested using an αvβ3-positive U87MG cell line. In vivo bio-distribution, anti-tumor activity, immunogenicity and toxicity were investigated in a nude mouse tumor model through repeated i.v. administration of cRGD-siEGFR (7 times over a 48?h interval). Analyses of in vitro data showed that cRGD-siEGFR silenced EGFR expression effectively, with high tumor targeting ability. Administration of cRGD-siEGFR to tumor-bearing nude mice led to significant inhibition of tumor growth, obvious reduction of EGFR expression and down-regulation of EGFR mRNA and protein in tumor tissue. Furthermore, serum biochemistry and pathological section evaluation did not indicate any serious toxicity of cRGD-siEGFR in vivo. cRGD-siEGFR is likely a promising candidate with high targeting ability, substantial anti-tumor effects and low toxicity in vitro and in vivo.     

中药多糖调控肿瘤微环境的研究进展

肿瘤微环境在肿瘤的发生、发展、转移等环节起到至关重要的作用。多种中药多糖通过调控肿瘤微环境而展现出抗肿瘤作用。从肿瘤微环境的各个组成部分如肿瘤相关成纤维细胞、肿瘤免疫细胞、血管内皮细胞、细胞外基质出发,阐述黄芪多糖、猪苓多糖、香菇多糖、车前子多糖、人参多糖、羊栖菜多糖和枸杞多糖对肿瘤微环境的调控作用,为抗肿瘤中药多糖药物的研发提供参考。     

Baicalein inhibits agonist- and tumor cell-induced platelet aggregation while suppressing pulmonary tumor metastasis via cAMP-mediated VASP phosphorylation along with impaired MAPKs and PI3K-Akt activation

Recently, the importance of platelet activation in cancer metastasis has become generally accepted. As a result, the development of new platelet inhibitors with minimal adverse effects is now a promising area of targeted cancer therapy. Baicalein is a functional ingredient derived from the root of Scutellaria baicalensis Georgi, a plant used intraditional medicine. The pharmacological effects of this compound including anti-oxidative and anti-inflammatory activities have already been demonstrated. However, its effects on platelet activation are unknown. We therefore investigated the effects of baicalein on ligand-induced platelet aggregation and pulmonary cancer metastasis. In the present study, baicalein inhibited agonist-induced platelet aggregation, granule secretion markers (P-selectin expression and ATP release), [Ca²⁺]_i mobilization, and integrin αIIbβ3 expression. Additionally, baicalein attenuated ERK2, p38, and Akt activation, and enhanced VASP phosphorylation. Indeed, baicalein was shown to directly inhibit PI3K kinase activity. Moreover, baicalein attenuated the platelet aggregation induced by C6 rat glioma tumor cells in vitro and suppressed CT26 colon cancer metastasis in mice. These features indicate that baicalein is a potential therapeutic drug for the prevention of cancer metastasis.     

半枝莲黄酮类化合物体外抗肿瘤活性的研究

目的 研究半枝莲中黄酮类化合物的体片抗肿瘤活性.方法 采用MTT法,测定半枝莲药材中的5个黄酮类化合物(木犀草素、野黄苓苷、黄苓素、芹莱素,4'-羟基汉黄苓素)休外分别对人肝癌细胞株HepG-2、人结肠癌细胞株SW480、人胃癌细胞株MGC-803、急性早幼拉细胞白血病细胞株HL-60、人红白血病细胞株K562的增殖抑...     

Protective effect of baicalein against endotoxic shock in rats in vivo and in vitro

Dried roots of Scutellaria baicalensis Georgi (Huang qin) are widely used in traditional Chinese medicine. Baicalein is a major bioactive flavonoid component of H. qin that shows a wide range of biological activities, including antioxidant and anti-inflammatory actions. We evaluated therapeutic effects and possible mechanisms of action of baicalein on circulatory failure and vascular dysfunction during sepsis induced by lipopolysaccharide (LPS; 10 mg/kg, i.v.) in anesthetized rats. Treatment of the rats with baicalein (20 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes of hypotension and tachycardia caused by LPS and significantly inhibited the elevation of plasma tumor necrosis factor alpha (TNF-alpha). Baicalein also decreased levels of inducible nitric oxide synthase (iNOS) and the overproduction of NO and superoxide anions caused by LPS. It also increased the survival rate of ICR mice (25-30 g) challenged by LPS (60 mg/kg). Moreover, infiltration of neutrophils into the liver and lungs of rats 6h after treatment with LPS was also reduced by baicalein. To investigate the mechanism of action of baicalein on sepsis, RAW 264.7 cells were used as a model. Baicalein inhibited iNOS protein production, and suppressed LPS-induced degradation of IkappaBalpha, the formation of a nuclear factor kappa B (NF-kappaB)-DNA complex and NF-kappaB-dependent reporter gene expression. Thus, the therapeutic effects of baicalein were associated with reductions in TNF-alpha and superoxide anion levels during sepsis. The inhibitory effects of baicalein on iNOS production may be mediated by inhibition of the activation of NF-kappaB. Baicalein may thus prove a potential agent against endotoxemia.