基于“成分-靶点-通路”的枸杞子调控年龄相关性黄斑变性作用机制研究

目的采用网络药理学方法探讨枸杞子改善年龄相关性黄斑变性(age-related macular degeneration,AMD)的活性成分及作用机制。方法以检索TCMSP数据库和查阅文献获得的枸杞子潜在活性成分为研究对象,通过Swiss Target Prediction平台、GeneCards数据库、OMIM数据库、DDT数据库和Drugbank数据库预测活性成分的潜在靶点;应用Metascape平台对潜在靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;运用String数据库和Cytoscape软件构建蛋白相互作用(protein-protein interaction,PPI)网络和"药物-成分-靶点-通路-疾病"网络;考察枸杞子不同提取部位对碘酸钠诱导的人视网膜色素上皮细胞ARPE-19活力的影响,以及对脂多糖诱导的小鼠小胶质细胞系BV2中炎症因子表达的影响。结果枸杞子中的88个活性成分通过调控血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、白细胞介素-8(interleukin-8,IL-8)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)等靶点,参与氧化应激、炎症反应等生物学过程,影响晚期糖基化终末产物(advanced glycation end products,AGE)-晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)、IL-17、TNF等信号通路发挥改善AMD的作用。枸杞子95%乙醇提取部位能够显著提高碘酸钠诱导的ARPE-19细胞活力(P<0.001),并显著降低脂多糖诱导的BV2细胞中IL-6、IL-1β、TNF-αmRNA表达水平(P<0.05、0.01、0.001)。结论枸杞子中多种成分具有影响AMD相关靶点的潜在作用,枸杞子能够通过改善氧化损伤、抑制炎症反应治疗AMD,为后续深入研究枸杞子中不同活性成分调节AMD的作用机制提供依据。     

健脾益肺膏方治疗小儿反复呼吸道感染肺脾两虚、卫表不固证的临床疗效分析

目的观察健脾益肺膏方治疗小儿反复呼吸道感染(RRTI)肺脾两虚、卫表不固证的临床疗效,探析其运用于小儿RRTI预后的可行性。方法将84例RRTI肺脾两虚、卫表不固证患儿随机分为治疗组和对照组,每组42例。治疗组患儿给予健脾益肺膏方口服治疗,对照组给予脾氨肽口服冻干粉口服治疗,疗程为3个月。观察2组患儿治疗前后血中免疫球蛋白IgG、IgA、IgM水平的变化情况,并评价2组的临床疗效及安全性。结果(1)治疗3个月后,治疗组总有效率为95.24%(40/42),对照组为76.19%(32/42);治疗组疗效明显优于对照组,差异有统计学意义(P<0.05)。(2)治疗后,2组患儿的血中IgG、IgA和IgM水平均较治疗前明显提高(P<0.05),且治疗组对患儿血中IgG、IgA和IgM水平的作用均明显优于对照组,差异均有统计学意义(P<0.05)。(3)治疗组的不良反应发生率为2.38%(1/42),对照组为7.14%(3/42),组间比较,差异无统计学意义(P>0.05)。结论健脾益肺膏方治疗小儿RRTI肺脾两虚、卫表不固证疗效确切,可有效改善患儿临床症状,提高患儿免疫功能,且具有较高的安全性,可用于小儿RRTI的临床预后治疗。     

须根水提液对白花丹参种子萌发幼苗光合作用及次生代谢的影响

目的:研究不同浓度白花丹参须根水提液对种子萌发、幼苗光合作用及次生代谢物质积累的影响,以期为白花丹参连作障碍的消减提供参考。方法:设置不同浓度白花丹参须根水提液处理组,测定不同处理组种子萌发率、幼苗多酚氧化酶活性、可溶性糖及可溶性蛋白含量;利用高效液相色谱法(HPLC)测定幼苗中水溶性及脂溶性有效物质含量。结果:白花丹参须根水提液低浓度对种子萌发有促进作用,高浓度有抑制作用;与对照组相比,处理组幼苗净光合速率、蒸腾速率、气孔导度均有不同程度下降;对照组多酚氧化酶活性及可溶性蛋白、可溶性糖总量分别比白花丹参须根水提液处理后低7.86%、8.47%、14.33%,但处理后幼苗水溶性有效成分(丹酚酸B、迷迭香酸)及脂溶性有效成分(二氢丹参酮、丹参酮Ⅰ、丹参酮Ⅱ_A、隐丹参酮)含量积累量均高于对照组。结论:白花丹参须根水提液通过影响种子的萌发率、抑制幼苗的光合作用、促进次生代谢产物积累影响丹参的产量及品质。     

川渝产黄连提取液颜色与有效成分相关性研究

目的探讨四川、重庆所产黄连的提取液颜色值与其有效成分的相关性。方法依据CIE L^*a^*b^*数字化系统,采用分光测色计测定色度值,HPLC测定有效成分含量。结果黄连的亮度与盐酸小檗碱、黄连碱呈显著负相关,红色方向与盐酸小檗碱、黄连碱呈显著正相关,且其黄色方向与盐酸小檗碱、巴马汀、黄连碱、表小檗碱的含量均呈显著正相关。结论黄连提取液的色度值与有效成分具有相关性,黄连提取液的色度值可以反映黄连的成分含量,为黄连建立简捷、快速质量评价技术方法奠定基础。     

茯苓、枸杞、黄芪提取物和海参冻干粉配伍增强免疫力作用的实验研究

目的:观察茯苓提取物、枸杞提取物、黄芪提取物和海参冻干粉配伍制成混合物的增强免疫力作用。方法:按《保健食品检验与评价技术规范》中免疫力功能检验方法,经口给予小鼠200 mg/(kg·bw)、400 mg/(kg·bw)、1000 mg/(kg·bw)剂量30 d,测定细胞免疫、体液免疫、单核-巨噬细胞吞噬功能指标及NK细胞活性。结果:高剂量组足跖肿胀度、抗体生成细胞数、半数溶血值、NK细胞活性、吞噬鸡红细胞的吞噬指数均显著高于阴性对照组(P<0.05),实验组能显著提高迟发型变态反应能力、小鼠抗体生成细胞数、血清溶血素水平、巨噬细胞吞噬鸡红细胞的能力和NK细胞活性。各剂量组对小鼠体质量增长、胸腺/体质量比值、脾脏/体质量比值、淋巴细胞增殖能力、单核-巨噬细胞碳廓清能力均无显著影响(P>0.05)。结论:茯苓提取物、枸杞提取物、黄芪提取物和海参冻干粉配伍制成的混合物具有增强免疫力作用。     

Evaluation of the usefulness of dimethicone and/or senna extract in improving the visualization of abdominal organs

Intestinal gas is the most common cause of technically unsatisfactory abdominal ultrasound scans. In the attempt to increase the visualization of abdominal organs, many investigators use antifoaming agents or laxatives. In the present, randomized, placebo-controlled, double-blind trial, a liquid dimethicone preparation and an extract of senna, alone and in combination, were tested as a means to improve scan quality. Response variables were defined on the basis of pancreas, aorta, and kidney visibility. There was no difference in the response variables of the three groups compared to placebo (P greater than 0.3-0.55). The results suggest that neither dimethicone nor senna improves the visibility of abdominal organs in ultrasound examination.     

银杏叶提取物对缺血-再灌流神经元损伤的保护作用及其信号转导机制

目的研究银杏叶提取物(EGB761)对缺糖缺氧/复糖复氧神经元损伤的保护作用,并探讨其主要细胞内信号转导机制。方法利用原代培养的皮层神经元,通过去除培养液中的糖和氧(oxygen and glucose deprivation,OGD)模拟缺血缺氧,恢复糖氧供给模拟再灌流。通过免疫蛋白印迹法测定Akt、磷酸化Akt(p-Akt)蛋白的表达。再灌流时加用银杏叶提取物(EGB761)观察其对神经元保护作用以及对Akt、p-Akt表达的调节作用。结果缺糖缺氧/复糖复氧后神经元p-Akt表达明显下降,EGB761可剂量依赖地保护神经元活性,并可上调因缺糖缺氧/复糖复氧而降低的p- Akt蛋白的表达,但该作用不被Ly294002所阻断。结论EGB761对培养的神经元缺糖缺氧/复糖复氧损伤有保护作用,该作用可能与非PI3K依赖的p-Akt信号转导通路激活有关。     

Korean Red Ginseng Extract Enhances the Anticancer Effects of Sorafenib through Abrogation of CREB and c‐Jun Activation in Renal Cell Carcinoma

Although application of sorafenib in the treatment of human renal cell carcinoma (RCC) remains one of the best examples of successful targeted therapy, majority of RCC patients suffer from its side effects as well as develop resistance to this targeted therapy. Thus, there is a need to promote novel alternative therapies for the treatment of RCC. In this study, we investigated whether Korean red ginseng extract (KRGE) could inhibit the proliferation and induce chemosensitization in human renal cancer cells. Also, we used a human phospho‐antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after KRGE and sorafenib combination treatment. Korean red ginseng extract suppressed the proliferation of two RCC cell lines; activated caspase‐3; caused poly(ADP‐ribose) polymerase cleavage; abrogated the expression of B‐cell lymphoma 2, B‐cell lymphoma extra large, survivin, inhibitors of apoptosis proteins‐1/2, cyclooxygenase‐2, cyclin D1, matrix metallopeptidase‐9, and vascular endothelial growth factor; and upregulated pro‐apoptotic gene products. Interestingly, KRGE enhanced the cytotoxic and apoptotic effects of sorafenib in RCC cells. The combination treatment of KRGE and sorafenib more clearly suppressed cyclic adenosine monophosphate response element‐binding protein and c‐Jun phosphorylation and induced phosphorylation of p53 than did the individual treatment regimen. Our results clearly demonstrate that KRGE can enhance the anticancer activity of sorafenib and may have a substantial potential in the treatment of RCC. Copyright © 2017 John Wiley & Sons, Ltd.