鞣花酸体外抗人脐静脉血管内皮细胞血管生成

目的观察鞣花酸体外抗人脐静脉血管内皮细胞(HUVEC)血管生成作用,以及对PDGFB,JAK/STAT表达的影响。方法采用SRB法、划痕法及Matrigel体外成管实验分别考察鞣花酸对HUVEC增殖、迁移及小管形成的影响;采用逆转录-聚合酶链(RT-PCR)法、酶联免疫法(ELISA)法、免疫印迹法(Western blot)分别观察鞣花酸对HUVEC细胞PDGFB mRNA表达、对细胞上清中PDGFB分泌及对细胞中PDGFB、STAT3、p-STAT3蛋白表达水平的影响。结果鞣花酸能显著抑制HUVEC增殖、迁移和小管形成(P0.01或P0.05),其增殖抑制作用呈时间和浓度依赖性,迁移和小管形成抑制作用呈剂量依赖性。同时,鞣花酸能显著降低PDGFB基因和蛋白表达水平(P0.01或P0.05),降低STAT3蛋白的磷酸化水平(P0.01或P0.05),而对STAT3蛋白表达总量无变化。结论鞣花酸可能通过下调内皮细胞中PDGFB的表达并进一步抑制下游STAT3蛋白磷酸化来抑制血管生成。     

蝎毒多肽提取物抑制H22肝癌血管生成的作用机制研究

目的探讨蝎毒多肽提取物抗肿瘤血管生成的机制。方法建立H22肝癌皮下荷瘤模型,随机分为荷瘤对照组（对照组）,蝎毒多肽提取物（polypeptide extract from scorpion venom,PESV）高、低剂量组,5－氟尿嘧啶（5-fluorouracil,5-Fu）组,每组10只。连续干预14天。绘制肿瘤体积生长曲线并计算抑瘤率;HE染色观察各组肿瘤组织病理变化;采用SP法检测各组肿瘤组织微血管密度（microvessel density,MVD）。采用免疫组织化学法及Western blot法检测各组磷脂酰肌醇-3-激酶（phosphatidylinositol 3-kinase,PI3K）、磷酸化蛋白激酶B （phosphoprotein kinase B,P-Akt）、缺氧诱导因子-1α（hypoxia-inducible factor-1α,HIF-1α）、血管内皮生长因子-A（vascular endothelial growth factor-A,VEGF-A）蛋白表达。结果5-Fu组,PESV高、低剂量组抑瘤率分别为64.8%、43.7%和32.4%。与对照组比较,三个给药组PI3K、P-Akt、HIF-1α、VEGF-A蛋白表达明显下调（P〈0.05,P〈0.01）,PESV高、低剂量组MVD均降低（P〈0.05）。结论PESV可抑制H22肝癌血管生成,其机制可能与抑制肿瘤微环境中PI3K、P-Akt、HIF-1α、VEGF-A的表达有关。     

血小板激活因子受体拮抗剂SY0916抑制巨噬细胞血管生成作用的研究

 目的 考察血小板激活因子（platelet activating factor,PAF受体拮抗剂SY0916对巨噬细胞释放血管内皮生成相关因子的影响,探讨SY0916抗血管生成的相关分子机制。方法 采用Boyden Chamber法检测小鼠腹腔巨噬细胞的趋化反应;放射性免疫分析法检测巨噬细胞U937上清中白细胞介素（IL-1β含量;L929生物测定法分析肿瘤坏死因子（TNF-α分泌;ELISA法测定血管内皮细胞生长因子（VEGF含量;明胶酶谱法检测间质金属蛋白酶（MMP-9活性;Western Blot法检测MMP-9蛋白表达;RT-PCR法观察IL-1β、TNF-α、VEGF mRNA的表达;凝胶电泳迁移率变更法（EMSA分析核转录因子（NF-κB活性。结果 SY0916对PAF诱导的小鼠腹腔巨噬细胞趋化反应具有显著的抑制作用;SY0916可呈剂量依赖性地抑制PMA刺激人U937巨噬细胞引起的IL-1β、TNF-α、VEGF的生成以及IL-1β、TNF-α、VEGF的mRNA表达;SY0916能显著抑制U937细胞MMP-9的活性及蛋白表达;SY0916明显抑制NF-κB的活化。结论 PAF受体拮抗剂SY0916可能通过抑制巨噬细胞NF-κB的活性而下调促血管生成因子和MMP的表达发挥抗血管生成的作用。     

绿萝花及其多糖对S180荷瘤小鼠肿瘤免疫相关因子的影响

目的探讨藏药绿萝花及绿萝花多糖对机体肿瘤免疫功能的影响,为绿萝花进一步开发利用提供科学依据。方法以S180荷瘤小鼠为研究对象,绿萝花水浸膏和水溶性粗多糖为研究材料,环磷酰胺为阳性对照,以肿瘤生长抑制率、胸腺指数、脾脏指数、白细胞介素-2(IL-2)、抗肿瘤坏死因子(TNF-α)、干扰素γ(IFN-γ)为检测指标。结果小鼠在接种S180肉瘤细胞后,血浆中IL-2、TNF-α、IFN-γ含量明显下降;灌服环磷酰胺后,胸腺指数和脾脏指数均下降,以脾脏指数下降明显,血浆IL-2、TNF-α、IFN-γ含量升高;囗服不同剂量绿萝花水浸膏及多糖后,胸腺指数和脾脏指数均增加,血浆IL-2、TNF-α、IFN-γ含量明显升高,尤以中剂量绿萝花水浸膏和多糖更为明显。结论不同剂量绿萝花及绿萝花多糖均具有抑制S180肉瘤生长的能力,均上调荷瘤小鼠血浆IL-2、TNF-α、IFN-γ的水平以增强机体的抗肿瘤效果,1.0 g/(kg·d)绿萝花干膏和100 mg/(kg·d)绿萝花多糖连续灌服14 d效果最好。     

红芪总多糖对小鼠S180瘤的抑制作用及其机制研究

目的:研究红芪总多糖(THPS)对小鼠S180瘤的抑制作用及其作用机制。方法:水提醇沉法从红芪根中提取THPS并测定其分子量、纯度和糖、糖醛酸含量及单糖组成。昆明小鼠90只随机分为9组,第1组作为正常组,另8组接种S180瘤后重新分别给予低、中、高不同剂量的THPS及THPS合环磷酰胺(CY)治疗,14 d后处死小鼠。测定每组小鼠的瘤重和抑瘤率,ELISA法测定每组小鼠外周血白介素2(IL-2)和肿瘤坏死因子α(TNF-α),免疫组化法测定肿瘤核转录因子κB(NF-κB)。结果:THPS中剂量对小鼠S180瘤有明显抑制作用,且与CY合用后有协同作用,并明显增高小鼠IL-2、TNF-α、NF-κB的含量。结论:中剂量的THPS具有抑制S180瘤作用,其机制通过增高IL-2、TNF-α和NF-κB发挥作用。     

蝎毒多肽提取物联合5 氟尿嘧啶对H22肝癌血管生成拟态形成的作用及机制研究

目的 观察蝎毒多肽提取物（polypeptide extract from scorpion venom, PESV）联合5-氟尿嘧啶（5-fluorouracil, 5-Fu）对小鼠H22肝癌移植瘤血管生成拟态（vasculogenic mimicry,VM）形成的抑制作用并探讨其可能的作用机制。方法 60只昆明小鼠,皮下接种H22肝癌细胞悬液建立荷瘤模型,随机分为荷瘤对照组、5-氟尿嘧啶组（5-Fu组）、联合组（PESV+5-Fu）,每组20只,连续干预14天,隔日测量肿瘤体积,绘制肿瘤体积增殖曲线,并计算抑瘤率;HE染色法观察肿瘤组织的形态学改变;免疫组织化学法和过碘酸雪夫氏染色（PAS）双标法检测各组肿瘤组织VM密度;免疫组织化学法检测缺氧诱导因子-1α（hypoxia inducible factor-1α,HIF-1α）、基质金属蛋白酶2（matrix metalloproteinase-2,MMP-2）的蛋白表达水平, 用LeicaQwinV3图像分析软件进行灰度值半定量分析。结果 联合组和5-Fu组H22肝癌移植瘤的生长较荷瘤对照组均受到明显抑制（P<0.05）,且联合组和5-Fu组瘤重和肿瘤体积亦存在显著差异（P<0.05）;免疫组织化学法和PAS双标法检测显示,联合组VM密度明显低于荷瘤对照组和5-Fu组（P<0.01）;与荷瘤对照组比较,联合组HIF-1α和MMP-2的蛋白表达水平均显著降低（P<0.01）。结论 PESV联合5-Fu可抑制小鼠H22肝癌移植瘤VM形成,其机制可能与抑制肿瘤微环境中HIF-1α和MMP-2的表达有关。     

地锦草调控NF-κB/VEGF信号通路抑制肿瘤血管生成的机制

目的:通过观察地锦草对H22肝癌小鼠核转录因子-κB/血管内皮生长因子(nuclear factor kappa-B/vascular endothelial growth factor,NF-κB/VEGF)信号通路相关蛋白的影响,探讨地锦草抑制肿瘤血管生成的机制。方法:昆明种小鼠皮下接种肝癌H22细胞建立H22肝癌小鼠模型,随机分为模型组,环磷酰胺组,地锦草组高、中、低剂量组。地锦草低、中、高剂量组分别灌胃(ig)给药1.13,2.25,4.50 g·kg~(-1),环磷酰胺组腹腔注射(ip)给药50 mg·kg~(-1),模型组和环磷酰胺组灌服相同体积的蒸馏水,14 d后处死小鼠,测量肿瘤质量和小鼠体质量,计算抑瘤率;免疫组织化学检测微血管密度标记物血小板-内皮细胞黏附分子31(platelet endothelial cell adhesion molecule-31,CD31),聚合酶链反应检测肿瘤组织NF-κB,肿瘤坏死因子(TNF)-α,VEGF mRNA表达,免疫组化检测NF-κB,TNF-α,VEGF蛋白表达。结果:与模型组比较,给予地锦草后,H22肝癌小鼠瘤重减轻(P0.01),地锦草高剂量组抑瘤率升高,高达59.1%(P0.01);肿瘤组织CD31表达明显下降(P0.01);肿瘤组织NF-κB,TNF-α,VEGF mRNA和蛋白表达均下降(P0.01)。结论:地锦草对H22肝癌小鼠肿瘤的抑制作用可能是通过减少肿瘤新生血管的生成,与减弱肿瘤组织的炎性因子表达有关。     

柿叶不同极性部位对H22腹水瘤及H22,S180实体瘤小鼠的抑瘤作用

目的:研究柿叶不同极性部位对小鼠H22及S180抑瘤作用的影响。方法:柿叶乙醇提取物分别用三氯甲烷、乙酸乙酯、正丁醇萃取,得到相应不同极性部位;乙醇提取后的柿叶晾干后水煮,得水提部位。分别建立H22腹水瘤小鼠模型和H22,S180实体瘤小鼠模型,将荷瘤小鼠随机分为空白组,模型组,环磷酰胺组(0.1 g·kg-1),不同极性部位(柿叶三氯甲烷、柿叶水提、柿叶乙酸乙酯、柿叶正丁醇)高、中、低剂量组,连续ig 10 d。观察各用药组对H22腹水瘤小鼠腹围、腹水抑制率和肝组织病理学形态的影响,以及对H22和S180实体瘤小鼠摄食量、体重、抑瘤率、生命延长率、胸腺和脾脏系数等的影响。结果:与模型组比较,柿叶乙酸乙酯部位、水提部位和正丁醇部位能明显减少H22腹水瘤小鼠的腹水量,不同程度改善肝细胞肿胀、溶解等状况;不影响H22和S180实体瘤小鼠的摄食量,能明显提高荷瘤小鼠的抑瘤率、延长生命延长率,增加胸腺系数和脾脏系数(P<0.01,P<0.05)。结论:柿叶乙酸乙酯部位、水提部位和正丁醇部位对H22和S180荷瘤小鼠有不同程度的抑瘤作用,可为柿叶抑瘤作用的有效部位。柿叶乙酸乙酯部位对肝癌H22小鼠(包括实体瘤和腹水瘤)的影响比对肉瘤S180小鼠更显著。     

地鳖纤溶蛋白对荷S180和H22小鼠的抑瘤作用研究

目的 研究地鳖虫纤溶活性先导蛋白(EFP)对荷S180和H22小鼠肿瘤的抑制作用.方法 通过体外实验,构建荷瘤小鼠模型,药物实验分为阳性对照组(环磷酰胺),阴性对照组(生理盐水),药物高浓度组、中浓度组和低浓度组.实体瘤通过瘤重计算抑瘤率,腹水瘤通过细胞浓度计算抑瘤率.结果 EFP对S180腹水瘤有较好的抑制率, 药剂量为2.90mg/kg的抑制率为69.56%,明显高于环磷酰胺(20mg/kg)的51.75%的抑制率;EFP对S180实体瘤有较好抑制作用,药剂浓度为1.45 g/kg时,抑制率为37.48%,高于环磷酰胺(20 mg/kg)的35.59%的抑制率,并呈现一定的药物剂量依赖性;药剂浓度为0.73 mg/kg时,对H22实体瘤抑瘤率为41%,高于环磷酰胺(20 mg/kg)的37%的抑制率.结论 EFP对荷S180和H22小鼠肿瘤有较好的抑制作用.     

脂麻花醇提物对S180和H22小鼠的抗肿瘤作用研究

目的：研究脂麻花醇提物对小鼠移植瘤的抗肿瘤作用。方法：观察脂麻花醇提物对小鼠肉瘤S180和肝癌H22的抗肿瘤作用，测定其对荷瘤小鼠免疫器官的影响。结果：6、3、1．5g／kg脂麻花醇提物对S180和H22小鼠瘤株均有明显抑制作用，但对荷瘤小鼠的胸腺指数、脾指数无明显影响。结论：脂麻花醇提物具有抗肿瘤作用，对S180小鼠和H22小鼠抑瘤率分别为25．2％～53．6％和27．1％～40．1％。     

中华眼镜蛇毒对荷S180小鼠抑瘤作用及其机制初探

采用腹腔注射NNAV的方法，观察其对荷S180小鼠瘤重和血浆一氧化氮（NO）以及脾系数的影响，结果表明：不同浓度的NNAV均可不同程序抑制肿瘤生长，其中低浓度疗效最好，且随着用药时间的延长，抑瘤作用更加明显。荷瘤对照组血浆中的NO含量明显高于正常对照组，用药后其含量明显降低，其中低浓度用药组恢复至正常水平。各用药组的脾系数均大于对组组，抑瘤率较高的用药组的脾系数大也较明显。NNAV的抑瘤作用可能与其降低荷瘤鼠血浆NO水平激活脾脏功能及增强免疫应答有关。     

桂皮醛经JAK2/STAT3通路抑制VEGF诱导的内皮细胞增殖、迁移及成管

目的:为探讨桂皮醛对糖尿病视网膜病变新生血管的作用及机制,观察了桂皮醛对血管内皮生长因子(VEGF)诱导EA. hy926细胞增殖、迁移、成管以及Janus激酶2/信号传导与转录激活因子3(JAK2/STAT3)通路的影响。方法:将EA.hy926细胞分成空白组、模型组(7μg·L-1VEGF),VEGF+桂皮醛(60,90,120,150μmol·L-1)组,分别采用噻唑蓝(MTT)比色法和划痕实验检测桂皮醛对VEGF诱导EA. hy 926细胞增殖和迁移作用的影响;将EA. hy 926细胞分成空白组,模型组(7μg·L-1VEGF),VEGF+桂皮醛(90,150μmol·L-1)组,采用管腔形成实验检测桂皮醛对VEGF诱导EA. hy 926细胞成管作用的影响;将EA. hy 926细胞分成空白组,模型组(7μg·L-1VEGF),VEGF+AG490 (50μmol·L-1)组,VEGF+桂皮醛(90μmol·L-1)组,VEGF+桂皮醛(150μmol·L-1)组,VEGF+桂皮醛(150μmol·L-1)+AG490(50μmol·L-1)组,采用蛋白免疫印迹法(Western blot)检测桂皮醛对VEGF诱导EA. hy 926细胞JAK2/STAT3通路的影响。结果:与空白组比较,模型组能够显著地促进EA. hy 926细胞增殖和迁移(P 0. 01)。与模型组比较,桂皮醛(60,90,120,150μmol·L-1)组能显著抑制VEGF诱导EA. hy 926细胞的增殖和迁移(P 0. 01)。与空白组比较,VEGF对EA. hy 926细胞成管具有一定的促进作用,成管的节点数、交叉点数、网眼数和血管分支数均有增加,但无统计学差异。与模型组比较,桂皮醛(90,150μmol·L-1)组对成管的节点数、交叉点数和网眼数均有明显抑制作用(P 0. 05,P 0. 01)。与空白组比较,模型组p-JAK2,p-STAT3,STAT3蛋白表达明显升高(P 0. 05,P 0. 01)。与模型组比较,桂皮醛(150μmol·L-1)能够显著抑制VEGF引起的p-JAK2,p-STAT3,STAT3蛋白表达升高(P 0. 01),桂皮醛(90μmol·L-1)能够显著抑制VEGF引起的p-STAT3,STAT3蛋白表达升高(P 0. 05,P 0. 01)。结论:桂皮醛对VEGF诱导EA. hy 926细胞的增殖、迁移、成管具有明显的抑制作用,该作用与抑制JAK2/STAT3通路的激活有关。     

石榴花对棕榈酸诱导的HepG2细胞脂质沉积的改善作用及机制研究

目的 探讨石榴花提取物（Punica granatum flower extract,PFE）及其活性成分白桦脂酸和木犀草素对棕榈酸诱导的人肝癌HepG2细胞脂质沉积的改善作用和作用机制。方法 通过CCK-8法测定棕榈酸、辛伐他汀、PFE、白桦脂酸和木犀草素对HepG2细胞活力的影响,以确定后续给药剂量。利用500μmol/L棕榈酸建立HepG2细胞脂质沉积模型,同时给予PFE(50、100、200 mg/L)、白桦脂酸（40、80、160μmol/L）、木犀草素（40、80、160μmol/L）进行干预,采用油红O染色法测定细胞内脂质含量;GPO-PAP法测定细胞内三酰甘油（triglyceride,TG）和总胆固醇（Total cholesterol,TC）含量;流式细胞仪检测早、晚期凋亡细胞率;Western blotting检测凋亡因子B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白（Bcl-2 associated X protein,Bax）及磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/...     

The genus Commiphora: a review of its traditional uses, phytochemistry and pharmacology

Ethnopharmacological relevance

The resinous exudates of the Commiphora species, known as ‘myrrh’, are used in traditional Chinese medicine for the treatment of trauma, arthritis, fractures and diseases caused by blood stagnation. Myrrh has also been used in the Ayurvedic medical system because of its therapeutic effects against inflammatory diseases, coronary artery diseases, gynecological disease, obesity, etc.

Aim of the review

Based on a comprehensive review of traditional uses, phytochemistry, pharmacological and toxicological data on the genus Commiphora, opportunities for the future research and development as well as the genus’ therapeutic potential are analyzed.

Methods

Information on the Commiphora species was collected via electronic search (using Pubmed, SciFinder, Scirus, Google Scholar and Web of Science) and a library search for articles published in peer-reviewed journals. Furthermore, information also was obtained from some local books on ethnopharmacology. This paper covers the literature, primarily pharmacological, from 2000 to the end of December 2011.

Results

The resinous exudates from the bark of plants of the genus Commiphora are important indigenous medicines, and have a long medicinal application for arthritis, hyperlipidemia, pain, wounds, fractures, blood stagnation, in Ayurvedic medicine, traditional Chinese medicine and other indigenous medical systems. Phytochemical investigation of this genus has resulted in identification of more than 300 secondary metabolites. The isolated metabolites and crude extract have exhibited a wide of in vitro and in vivo pharmacological effects, including antiproliferative, antioxidant, anti-inflammatory and antimicrobial. The bioactive steroids guggulsterones have attracted most attention for their potent hypolipidemic effect targeting farnesoid X receptor, as well as their potent inhibitory effects on tumor cells and anti-inflammatory efficiency.

Conclusions

The resins of Commiphora species have emerged as a good source of the traditional medicines for the treatment of inflammation, arthritis, obesity, microbial infection, wound, pain, fractures, tumor and gastrointestinal diseases. The resin of C. mukul in India and that of C. molmol in Egypt have been developed as anti-hyperlipidemia and antischistosomal agents. Pharmacological results have validated the use of this genus in the traditional medicines. Some bioassays are difficult to reproduce because the plant materials used have not been well identified, therefore analytical protocol and standardization of extracts should be established prior to biological evaluation. Stem, bark and leaf of this genus should receive more attention. Expansion of research materials would provide more opportunities for the discovery of new bioactive principles from the genus Commiphora.     

Herbal medicines for the prevention of alcoholic liver disease: A review

Ethnopharmacological relevance

Long-term excess alcohol exposure leads to alcoholic liver disease (ALD)—a global health problem without effective therapeutic approach. ALD is increasingly considered as a complex and multifaceted pathological process, involving oxidative stress, inflammation and excessive fatty acid synthesis. Over the past decade, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of ALD, due to their multiple targets and less toxic side effects. Several herbs, such as Cnidium monnieri (L.) Cusson (Apiaceae), Curcuma longa L. (Zingiberaceae) and Pueraria lobata (Willd.) Ohwi (Leguminosae), etc., have been shown to be quite effective and are being widely used in China today for the treatment of ALD when used alone or in combination.

Aim of the review

To review current available knowledge on herbal medicines used to prevent or treat ALD and their underlying mechanisms.

Materials and methods

We used the pre-set searching syntax and inclusion criteria to retrieve available published literature from PUBMED and Web of Science databases, all herbal medicines and their active compounds tested on ALD induced by both acute and chronic alcohol ingestion were included.

Results

A total of 40 experimental studies involving 34 herbal medicines and (or) active compounds were retrieved and reviewed. We found that all reported extracts and individual compounds from herbal medicines/natural plants could be beneficial to ALD, which might be attributed to regulate multiple critical targets involved in the pathways of oxidation, inflammation and lipid metabolism.

Conclusions

Screening chemical candidate from herbal medicine might be a promising approach to drug discovery for the prevention or treatment of ALD. However, further studies remain to be done on the systematic assessment of herbal medicines against ALD and the underlying mechanisms, as well as their quality control studies.