Determination of inhibitory activity of Salvia miltiorrhiza extracts on xanthine oxidase with a paper-based analytical device

A novel paper-based analytical device(PAD)was prepared and applied to determine the xanthine oxidase(XOD)inhibitory activity of Salvia miltiorrhiza extracts(SME).First,polycaprolactone was 3D printed on filter paper and heated to form hydrophobic barriers.Then the modified paper was cut according to the specific design.Necessary reagents including XOD for the colorimetric assay were immobilized on two separate pieces of paper.By simply adding phosphate buffer,the reaction was performed on the double-layer PAD.Quantitative results were obtained by analyzing the color intensity with the specialized device system(consisting of a smartphone,a detection box and sandwich plates).The 3Dprinted detection box was small,with a size of 9.0 cm×7.0 cm×11.5 cm.Color component G performed well in terms of linearity and detection limits and thus was identified as the index.The reaction conditions were optimized using a definitive screening design.Moreover,a 10%glycerol solution was found to be a suitable stabilizer.When the stabilizer was added,the activity of XOD could be maintained for at least 15 days under 4℃ or-20℃ storage conditions.The inhibitory activity of SME was investigated and compared to that of allopurinol.The results obtained with the PAD showed agreement with those obtained with the microplate method.In conclusion,the proposed PAD method is simple,accurate and has a potential for point-of-care testing.It also holds promise for use in rapid quality testing of medicinal herbs,intermediate products,and preparations of traditional Chinese medicines.

Informatics-based prediction of molecular networks targeted by active ingredients in Danshen (Salvia miltiorrhiza)

Salvia miltiorrhiza (Chinese, Danshen) is one of the most famous traditional herbs, and has been used to treat cardiovascular disease. Despite the wide application of Danshen in China, the mechanisms of its bioactive components are poorly understood. The present study used bioinformatics to identify possible mechanisms by which Danshen treats cardiovascular disease. Possible human protein targets of Danshen were identified in the PubChem database, possible human gene targets of cardiovascular disease were identified in the NCBI database, and then both sets of targets were analyzed using Ingenuity Pathway Analysis to predict molecular networks affected by Danshen in cardiovascular disease. The results suggest that signaling proteins affected by Danshen in cardiovascular disease, which include FASN, PAFAH1B2, PLA2G7, PAFAH1B3 and IL1B, are involved primarily in LXR/RXR activation, atherosclerosis signaling, hepatic fibrosis/hepatic stellate cell activation, acute phase response signaling. The main networks affected by Danshen are predicted to involve in cellular movement, immune cell trafficking, hematological system development and function;DNA replication, recombination, and repair, cancer, hematological disease;cardiovascular disease, organismal injury and abnormalities, tissue morphology.These results identify several specific proteins and pathways that may be affected by Danshen in cardiovascular disease, and they illustrate the power of integrative bioinformatics and chemical fragment analysis for focusing mechanistic studies.

Tyrosine Aminotransferase Gene (SmTAT) Revealed Genetic Diversity and Phylogeny of Cultivated Danshen (Salvia miltiorrhiza) Populations

Chinese traditional medicine Danshen is the radix of the perennial herbs of Salvia miltiorrhiza Bunge, which has a variety of pharmacological effects and is traditionally and extensively applied clinically to treat cardiovascular disorders. In this research, the genomic genes for tyrosine aminotransferase (TAT) of 38 cultivated populations of Danshen in China were cloned and bioinformatic analyses were conducted to reveal its genetic diversity and phylogeny. The full-length SmTAT was 2296 - 2444 bp including 6 exons (encoding 411 amino acids) and 5 introns. Overall, the SmTAT genes in cultivated Danshen populations are highly conserved with a relative low level of genetic diversity. The spliced exons (1236 bp) had 23 SNP variations with a rate of 1.86%, of which 22 occurred in the white flower S. miltiorrhiza Bge.f.alba population (W-SCHY-W-1) and led to 5 amino acid variations. The entire 290 SNP variations with a rate of 24% in the 5 introns occurred exclusively in W-SCHY-W-1. Phylogenetic trees based on the full-length, combined introns, the spliced exons, and the deduced amino acid sequences of SmTAT all showed a two-clade basic structure with W-SCHY-W-1 uniquely standing alone. The SmTAT gene of the white flower population (W-SCHY-W-1) is unique and especially rich in variations. The first time clarified genomic SmTAT gene structure and genetic diversity in cultivated Danshen populations laid an excellent foundation for further studies on the biosynthesis of bioactives and the molecular breeding of Danshen as well as in plant tyrosine metabolism.

丹参(Salvia miltiorrhiza)中一对具有新奇结构的立体异构体的结构测定

为了进一步弄清丹参的化学成分，应用化学和色谱分离方法从丹参中分离到一个白色粉末固体，经综合运用先进的波谱分析手段，包括１Ｈ－１ＨＣＯＳＹ、１Ｈ－１３ＣＣＯＳＹ、ＣＯＬＯＣ、ＮＯＥ等二维核磁共振谱确定了它们的化学结构为一对具有螺环缩酮内酯结构的新二萜类立体异构体化合物．

Progress in research into the mechanism of Radix salviae miltiorrhizae in treatment of acute pancreatitis

BACKGROUND: Acute pancreatitis (AP) is a common acute abdomen with high mortality, multiple complications and complicated causes. There is no effective therapy for AP. Radix salviae miltiorrhizae (Danshen), a traditional herbal medicine, has a low price and a wide range of clinical applications. It is effective to promote blood flow, eliminate stagnancy, and relieve pain. It is also found to be effective in treating AP. We reviewed the progress in research into the mechanism of Radix salviae miltiorrhizae in treatment of AP. DATA SOURCES: An english-language literature search was conducted using MEDLINE (1988-2005) on Radix salviae miltiorrhizae (Danshen) and acute pancreatitis. RESULTS: The mechanisms of Danshen in the treatment of AP include improvement of microcirculatory disturbances; elimination of oxygen free radicals; modulation of the metabolism of lipid inflammatory mediator; and blocking of calcium inflow and prevention of calcium overload.CONCLUSION: Danshen can effectively reduce the mortality and complications of AP.

Salvia miltiorrhiza extract may exert an anti-obesity effect in rats with high-fat diet-induced obesity by modulating gut microbiome and lipid metabolism

BACKGROUND Studies have shown that a high-fat diet(HFD) can alter gut microbiota(GM)homeostasis and participate in lipid metabolism disorders associated with obesity.Therefore, regulating the construction of GM with the balance of lipid metabolism has become essential for treating obesity. Salvia miltiorrhiza extract(Sal), a common traditional Chinese medicine, has been proven effective against atherosclerosis, hyperlipidemia, obesity, and other dyslipidemia-related diseases.AIM To investigate the anti-obesity effects of Sal in rats with HFD-induced obesity, and explore the underlying mechanism by focusing on GM and lipid metabolism.METHODS Obesity was induced in rats with an HFD for 7 wk, and Sal(0.675 g/1.35 g/2.70g/kg/d) was administered to treat obese rats for 8 wk. The therapeutic effect was evaluated by body weight, body fat index, waistline, and serum lipid level. Lipid factors(cAMP, PKA, and HSL) in liver and fat homogenates were analyzed by ELISA. The effect of Sal on GM and lipid metabolism was assessed by 16S rRNAbased microbiota analysis and untargeted lipidomic analysis(LC-MS/MS),respectively.RESULTS Sal treatment markedly reduced weight, body fat index, serum triglycerides(TG), total cholesterol(TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein(HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as c AMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita. Furthermore, LC-MS/MS analysis indicated that Sal decreased TGs(TG18:2/18:2/20:4, TG16:0/18:2/22:6), DGs(DG14:0/22:6, DG22:6/22:6), CL(18:2/18:1/18:1/20:0), and increased ceramides(Cers;Cer d16:0/21:0, Cer d16:1/24:1),(O-acyl)-ω-hydroxy fatty acids(OAHFAs;OAHFA18:0/14:0) in the feces of rats. Spearman’s correlation analysis further indicated that TGs, DGs, and CL were negatively related to the abundance of Facklamia and Dubosiella, and positively correlated with Blautia and Quinella, while OAHFAs and Cers were the opposite.CONCLUSION Sal has an anti-obesity effect by regulating the GM and lipid metabolism.

Compound Astragalus and Salvia miltiorrhiza extract exerts anti-tumor activity by intervening the interaction of microRNA-145/microRNA-21 and Smad3C/3L phos-phorylation in hepatocellular carcinoma

OBJECTIVBE To investigate the intervention of compound Astragalus and Salvia miltiorrhiza extract(CASE) consisted of astragalosides,astragalus polysaccharides and salvianolic acids on the interaction of microRNA-145/microRNA-21(miR-145/miR-21) and Smad3 C/3 L phosphorylation(pSmad3 C/pSmad3 L) down-stream of transforming growth factor-β(TGF-β)/mitogen activated protein kinase(MAPK) signaling in hepatocellular carcinoma(HCC) progression by in vitro and in vivo experi.ments.METHODS In HepG2 cells and xenografts of nude mice,antagomir/agomir and plasmids of Smad3 C/3 L phosphorylation site mutation(Smad3 3 S-A/Smad3 EPSM) were used to intervene miR-145/miR-21 and pSmad3 C/pSmad3 L expression respectively,then incorporative CASE treatment.Cell proliferation,migration,apoptosis,tumor growth and histopathologic characteristics of xenografts,relevant proteins of TGF-β/Smad pathway and miR-145/miR-21 were evaluated.RESULTS CASE up-regulated miR-145 while down-regulated miR-21,inhibited cell proliferation,migration and tumor growth,accelerated cell apoptosis in HepG2 cells respectively transfected with Smad3 WT,Smad3 EPSM,Smad3 3 S-A plasmids in cultured dishes and xenografts of nude mice,the above effects were more evident in HepG2 cells with increased pSmad3 C.In TGF-β1-stimulated HepG2 cells and xenografts of nude mice,CASE antagonized the facilitating effects of miR-145 antagomir/miR-21 agomir on cell migration,proliferation,tumor growth and inhibiting effects of miR-145 antagomir/miR-21 agomir on cell apoptosis;CASE increased miR-145 down-regulated by miR-145 antagomir and decreased miR-21 up-regulated by miR-21 agomir,reduced protein level of pSmad3 L and their proteins including TβRⅡ,pERK1/2,pJNK1/2 and pp38 while elevated pSmad3 C expression.CONCLUSION These results suggest that pSmad3 C/pSmad3 L maybe interact with miR-145/miR-21 in HCC progression,which may be one of important molecular mechanisms of CASE's anti-HCC effects.

胆汁酸诱导胃癌的发生机制及丹参提取物潜在作用的研究进展

胆汁反流可导致胃黏膜发生炎性反应、癌变。胆汁酸可以通过激活各种受体和信号通路来诱导胃癌的发生。传统中药丹参提取物可以起到预防胆汁酸诱导胃癌的作用。文章对近年来胆汁酸在胃癌发生中的作用机制进行分析,胃黏膜长时间暴露于胆汁酸中会导致黏膜损伤及炎性反应,导致慢性胃炎、肠化生、异型增生和胃癌;丹参提取物在预防和治疗胆汁酸诱导的胃癌中具有潜在优势,丹参素通过调节多种涉及炎症、氧化应激、DNA损伤和细胞凋亡的信号通路,可以预防胆汁反流引起胃炎和胃癌。

丹参对糖尿病肾病保护作用及机制研究

糖尿病肾病(diabetes nephropathy,DN)是导致终末期肾脏病的首位致病因素,严重威胁患者生命健康。传统中医药在糖尿病肾病的治疗中具有重要潜力作用,丹参作为活血化瘀药代表,具有活血祛瘀、清心除烦之功。经研究发现,丹参含有丹酚酸、丹参酮、挥发油、多糖、含氮类化合物等多种成分,能够通过多途径多靶点改善肾小球超滤过状态和间质纤维化等病理改变,其中丹酚酸类和丹参酮类是丹参发挥糖尿病肾病保护作用的主要生物活性成分,具有降糖、调脂、抗炎、抗氧化应激、改善血流动力学、纠正肠道菌群紊乱、调节自噬水平等多种药理作用。该文参考近年来丹参相关制剂干预糖尿病肾病的临床研究和动物实验,对丹参在糖尿病肾病发生发展过程中起到的作用机制进行归纳总结,以期为临床应用丹参治疗糖尿病肾病提供更好的治疗策略和理论依据。

山楂丹参分散片的制备工艺研究

目的考察山楂丹参分散片最佳制备工艺。方法以丹参药材中丹参素钠、山楂药材中金丝桃苷为指标,采用L_(9)(3^(4))正交试验设计,对丹参、山楂提取工艺开展研究;通过对山楂丹参分散片中填充剂、润湿剂、崩解剂的考察,以分散均匀度为考察指标,对山楂丹参分散片处方和工艺进行筛选。结果山楂丹参分散片的最佳制备工艺为取丹参药材,加10倍量水回流提取3次,每次2 h,取山楂药材,用10倍量75%乙醇回流提取2次,每次1 h,分别将药液浓度至1.0 g/mL,并通过AB-8型大孔吸附树脂柱洗脱、浓缩、干燥,将上述丹参、山楂提取物混匀,过80目筛,再分别加入微晶纤维素、硫酸钙、羧甲基纤维素钠、交联羧甲基纤维素钠(过100目筛),混合均匀,以50%乙醇为黏合剂,24目筛制粒,60℃干燥。结论按最佳制备工艺制备的丹参、山楂提取物中丹参素钠、金丝桃苷含量较高;山楂丹参分散片在3 min内分散均匀,各项指标均符合2020年版《中华人民共和国药典》(四部)规定,表明山楂丹参分散片制备工艺稳定可行,筛选处方合理,可进一步研发。

丹参品种、产地及栽培历史本草考证

丹参为我国常用大宗中药材,历代本草均有记载,药用历史悠久,功效显著,具有活血止痛、宁心安神的作用,为常用活血化瘀药,临床医疗价值较高,在治疗心肌缺血、改善肝功能、保护肾脏、对抗肿瘤等方面具有较好的效果。查阅文献发现,近年来对丹参的研究大多集中在药理成分、临床等方面,鲜有从古籍文献出发对丹参品种、产地及栽培历史进行研究。通过系统查阅丹参古今文献发现,丹参近缘品种较多,在民间应用和地方入药中同属多种植物的根均作丹参用;在清代以前为野生丹参,清代以后才出现人工栽培丹参,以山东、四川丹参质量最好;各地虽有栽培,但是栽培品种混杂,品质退化严重,质量参差不齐,为此,有必要对丹参的品种、产地及栽培历史进行考证,为丹参正本清源及资源的进一步开发利用提供理论基础和现实依据。

基于离子液体原位泡腾萃取法在丹参及西洋参克百威残留分析中的应用

本研究建立了一种新颖的基于酸性离子液体的原位泡腾萃取技术的前处理方法。酸性离子液体1-丁基-3-甲基咪唑硫酸氢盐呈酸性,能与碳酸氢盐反应产生二氧化碳,起到泡腾萃取的效果,它还能与六氟磷酸铵发生离子交换作用而置换成疏水性离子液体1-丁基-3-甲基咪唑六氟磷酸盐,使其与水相分离,通过离心获取萃取相,最后通过高效液相色谱仪测定萃取相中农药的含量。考察了酸性离子液体、碳酸氢钠和氯化钠用量对萃取效率的影响,最终所得最佳条件为200 mg酸性离子液体、0.4 g碳酸氢钠和1.0 g氯化钠。在最优条件下,克百威的线性范围为0.3~4.0μg/mL,日内和日间的相对偏差(RSD)为4.6%和10.2%,丹参和西洋参在4.0μg/mL加标水平下,加标回收率为94.7%(西洋参)和74.6%(丹参),将此方法可用于不同基质中药材和饮片中农药残留的处理。

Short-term effect of Salvia miltiorhiza in treating rat acetic acid chronic gastric ulcer and long-term effect in preventing recurrence

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丹参总黄酮提取工艺的优化及其抑菌活性研究

通过单因素实验对超声提取法和热回流提取法提取丹参总黄酮工艺进行了比较研究,确定超声提取法优于热回流提取法,再通过响应面法进一步优化丹参总黄酮的超声提取工艺,并研究了丹参总黄酮对革兰氏菌的抑制活性。结果表明,最佳超声提取工艺条件为:料液比1∶10(g∶mL)、提取时间22 min、提取温度68℃、乙醇体积分数86%,在此条件下,丹参总黄酮提取率为4.140 mg·g^(-1);丹参总黄酮对革兰氏菌的抑制作用大小为:大肠埃希菌>金黄色葡萄球菌>铜绿假单胞菌。

Experimental study on the effect of Huangqi and Danshen ultramicro gel on vascular healing of wound in rats based on network pharmacology

Objective:To explore the effective components of Huangqi(Astragalus membranaceus(Fisch.)Bge.)and Danshen(Salvia miltiorrhiza Bge.)and predict their potential functional targets,to explore the effect and mechanism of Huangqi and Danshen ultrafine granule gel on wound vascular healing in rats by network pharmacology and experimental verification.Methods:Using the TCMSP database to screen the active components of two herbs and their potential targets,to search the target related to vascular injury through the Gene Card database,and to select the gene target with correlation coefficient greater than 10%.Then map the disease related target to the potential target of the compound,to obtain the common target,and to import the information to the String online analysis platform and Cytoscape to make the PPI map,and to carry on the topological analysis,KEGG and GO enrichment analysis through Metascape platform.The expression analysis of the main target genes of network pharmacology was verified by pathological section staining and optical density method to determine the content of vascular endothelial growth factor(VEGF)in tissues,the number of tissue new capillaries,and the wound healing rate.Results:A total of 115 active components and 297 target genes were selected from Huangqi and Danshen,and 123 target genes were intersected with vascular injury,among which IL6,AKT1,INS,VEGFA,TNF,EGF,CASP3,MAPK1,TP53 were the active genes with the highest intersection value.The pathways involved are mainly related to AGE-RAGE signaling pathway in diabetic complications,MAPK signaling pathway,Pathways in cancer,human cytomegalovirus infection,Fluid shear stress and atherosclerosis,Endocrine resistance,foxo signaling pathway etc.We experimentally validated VEGFA based on the primary target of vascular regeneration,the experimental results showed that there was different expression of VEGFA proteins in wound vascular healing process,and the quercetin,daidzein,luteolin,apigenin,tanshinone i of 115 active components were selected as the main compounds acting on the VEGFA.Conclusion:This study systematically reveals the material basis and mechanism of Huangqi and Danshen regulating wound vascular healing through multi-component,multi-target and multi-pathway and provides theoretical and scientific basis for the clinical application of Huangqi and Danshen.

衡水湖黄顶菊对丹参根腐病菌的抑制效应研究

本研究以衡水湖常见入侵菊科植物黄顶菊为试验材料,利用超声波细胞破碎法在不同乙醇浓度、不同料液比、不同提取时间、不同提取功率提取条件下制取黄顶菊提取液,然后对丹参根腐病菌进行抑菌试验,根据抑菌率确定最佳的提取条件。结果表明:最佳乙醇提取浓度为75%,最佳料液比为1∶10,最佳提取时间为100 min,最佳提取功率为30%。通过最大限度提取黄顶菊中有效抑菌成分,可为丹参根腐病病害的有效控制以及菊科外来入侵植物的防治开辟一条新途径,实现经济、有效、环保的生态防控。

丹参提取物、蒲公英提取物及其复方对肉鸡生长性能、免疫功能和抗氧化能力的影响

本试验旨在探究丹参提取物、蒲公英提取物及其复方对肉鸡生长性能、免疫功能和抗氧化机能的影响。选取192只1日龄雄性科宝-500肉鸡,随机分成4组,每组6个重复,每个重复8只鸡。对照组饲喂基础饲粮,试验组分别在基础饲粮中添加0.1%的丹参提取物(丹参提取物组)、0.1%的蒲公英提取物(蒲公英提取物组)、0.05%的丹参提取物+0.05%的蒲公英提取物(复方组)。试验期42 d。结果显示:1)与对照组相比,22~42日龄,复方组肉鸡的平均日增重显著提高(P<0.05),蒲公英提取物组和复方组肉鸡料重比显著降低(P<0.05);1~42日龄,试验组肉鸡的平均日增重均显著提高(P<0.05),料重比均显著降低(P<0.05)。2)与对照组相比,42日龄时,丹参提取物组和复方组肉鸡胸腺指数显著提高(P<0.05),且复方组肉鸡脾脏指数显著提高(P<0.05)。各试验组之间相比,复方组肉鸡42日龄脾脏指数显著高于蒲公英提取物组(P<0.05);与对照组相比,试验组肉鸡21日龄血清免疫球蛋白A(IgA)、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)含量和42日龄血清IgG、IgM含量均极显著提高(P<0.01),且复方组肉鸡42日龄血清IgA含量显著提高(P<0.05);试验组肉鸡21和42日龄血清溶菌酶(LZM)活性均显著提高(P<0.05);蒲公英提取物组和复方组肉鸡21和42日龄血清新城疫抗体效价显著提高(P<0.05)。各试验组之间相比,复方组肉鸡21日龄血清IgA、IgG、IgM含量和42日龄血清IgG、IgM含量极显著高于丹参提取物组和蒲公英提取物组(P<0.01)。3)与对照组相比,蒲公英提取物组和复方组肉鸡21日龄血浆谷胱甘肽过氧化物酶(GSH-Px)活性显著提高(P<0.05),试验组肉鸡42日龄血浆GSH-Px活性均极显著提高(P<0.01),丹参提取物组和复方组肉鸡21和42日龄血浆丙二醛(MDA)含量显著降低(P<0.05)。各试验组之间相比,复方组肉鸡42日龄血浆MDA含量显著低于蒲公英提取物组(P<0.05)。综上所述,饲粮中单独添加0.1%的丹参提取物或蒲公英提取物以及二者同时添加(0.05%丹参提取物+0.05%蒲公英提取物)均可增强肉鸡的免疫功能,提高抗氧化能力,从而改善生长性能,且丹参提取物与蒲公英提取物同时添加效果优于单独添加。

黄芪丹参提取物改善急性呼吸窘迫综合征大鼠肺损伤的作用和机制研究

目的通过大鼠在体研究明确黄芪丹参提取物对急性呼吸窘迫综合征(acute respiratory distress syndrme,ARDS)大鼠肺损伤的影响及作用机制。方法通过慢病毒途径在大鼠肺部靶向沉默白细胞介素(interleukin,IL)4Rα,经黄芪丹参提取物给药后通过油酸与脂多糖(lipopolysaccharide,LPS)联合诱导建立大鼠ARDS模型,造模后6 h应用称重法检测肺组织湿干重比,HE染色评估肺组织病理学改变,酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中肿瘤坏死因子(tumor necrosing factor,TNF)-α、IL-1β、IL-6含量以及肺组织中髓过氧化物酶(myeloperoxidase,MPO)活性。流式细胞术检测BALF来源中性粒细胞凋亡率。免疫印迹法检测BALF来源中性粒细胞中IL-4Rα及半胱氨酸蛋白酶3水解体(Caspase 3-cleaved)蛋白表达,荧光定量PCR检测肺组织中趋化因子含量。结果与假手术组比较,ARDS模型组大鼠肺组织湿干重比明显增加(P<0.01),肺组织损伤评分明显升高(P<0.01),BALF中炎症因子TNF-α、IL-1β和IL-6含量和肺组织中MPO含量明显升高(P<0.01)。BALF来源中性粒细胞凋亡率稍降低(P>0.05)。IL-4Rα与Caspase 3-cleaved蛋白表达明显减弱(P<0.01)。肺组织中趋化因子CCL2、CCL3和CCL17 m RNA表达量明显增加(P<0.01)。10 mg/(kg·d)和30 mg/(kg·d)黄芪丹参提取物连续3 d灌胃给药能够明显改善上述指标的异常变化(P<0.05,P<0.01)。IL-4Rα沉默能有效逆转黄芪丹参提取物的上述作用(P<0.05,P<0.01)。结论黄芪丹参提取物能够通过上调IL-4Rα表达并间接诱导ARDS大鼠肺部中性粒细胞凋亡诱导因子Caspase 3-cleaved表达而导致中性粒细胞程序性坏死,并最终有效降低肺部炎症因子释放和减轻ARDS导致的大鼠肺损伤。

基于HIF-1α/VEGF信号通路探讨丹参提取物对糖尿病视网膜病变大鼠模型的影响

目的 探讨丹参提取物通过低氧诱导因子-1α (Hypoxic inducible factor-1α,HIF-1α)/血管内皮生长因子(Vascular endothelial growth factor, VEGF)信号通路对糖尿病视网膜病变(Diabetic retinopathy, DR)大鼠模型的影响。方法 高脂高糖饲养+腹腔注射链脲佐菌素(Streptozotocin, STZ)建立DR大鼠模型,将其分为模型对照组、阳性对照组(芪明颗粒1.42 g/kg)、丹参水提物组(0.16 g/kg)和丹参酮提取物组(0.12 g/kg),连续灌胃4周,然后检测大鼠的空腹血糖(Fasting blood glucose, FBG)、甘油三酯(Triglyceride, TG)、总胆固醇(Total cholesterol, TC)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol, LDL-C)和高密度脂蛋白胆固醇(High density lipoprotein cholesterol, HDL-C)的水平;HE染色观察视网膜组织形态变化,测量视网膜外核层(Outer nuclear layer, ONL)、内核层(Inner nuclear layer, INL)和神经节细胞层(Ganglion cell layer, GCL)的厚度;酶联免疫吸附测定法(Enzyme linked immunosorbent assay, ELISA)检测血清中糖化血红蛋白(Glycosylated hemoglobin, HbA1c)、糖基化终末产物(Advanced glycation end products, AGEs)和视网膜中白细胞介素-1β (Interleukin-1β,IL-1β)、白细胞介素-10 (Interleukin-10,IL-10)、肿瘤坏死因子-α (Tumor necrosis factor-α,TNF-α)与转化生长因子-β1 (Transforming growth factor-β1,TGF-β1)的水平,免疫组化法检测视网膜中HIF-1α和VEGF的表达。结果 较正常对照组,模型对照组中视网膜组织结构排列紊乱,各结构层厚度减少,FBG、TG、TC和LDL-C水平显著上升(P<0.01),HDL-C水平显著下降(P<0.05),血清中HbA1c和AGEs水平显著升高(P<0.01),视网膜中IL-1β、TNF-α、TGF-β1、HIF-1α和VEGF表达水平显著升高(P<0.01),IL-10表达水平显著降低(P<0.01);与模型对照组相比,丹参水提物和丹参酮提取物减轻了视网膜组织病变程度,降低了血糖和血脂的水平(P<0.05或P<0.01),减少了血清中HbA1c和AGEs的含量(P<0.01),IL-10和TGF-β1改善无统计学意义,IL-1β、TNF-α、HIF-1α和VEGF表达降低(P<0.05或P<0.01)。结论 丹参提取物能改善DR大鼠视网膜组织的病变,其机制可能是改善血糖血脂、炎性反应以及抑制HIF-1α/VEGF通路。

丹参抗肝癌潜在机制的研究进展

肝癌是第五大最常见的癌症类型之一,也是全球癌症相关死亡的第二大原因,由于其病因隐匿,难以在早期诊断,导致发病率和死亡率趋势不断上升。手术切除、射频消融、经动脉化疗栓塞、肝移植、全身化疗以及分子靶向药物治疗带来良好治疗效果的同时也带来许多不良反应。通过阅读国内外文献发现,丹参能通过多种途径发挥抗肝癌的作用,包括促进肝癌细胞分化和凋亡、降低肝癌细胞转移和侵袭能力、抑制血管生成、增强药物疗效、降低耐药性以及减少不良反应等。就丹参发挥抗肝癌的潜在机制进行了论述,旨在为丹参治疗肝癌类药物的研发以及临床实践提供理论依据。