Effects of Mangiferin on the Expression of TNF-α,iNos,ICAM-1 and Its mRNA in the Heart,Brain and Kidneys of SHR

[Objectives] To study the effects of Mangiferin( MGF) on TNF-α,iNOS,ICAM-1 and its mRNA expression in the heart,brain and kidneys of spontaneously hypertensive rats( SHR),and reveal the mechanism of its anti-inflammatory injury in hypertension target organs.[Methods]SHRs were randomly divided into 5 groups: the model group,the high-dose,medium-dose,low-dose MGF groups and the Benazepril group,with 8 rats in each group,WKY rats were used for the normal control group. Besides,on-invasive blood pressure( BP) instruments were used to measure systolic blood pressure in the rats' tail artery,western blot was used to analyze the expression of TNF-α,iNOS,ICAM-1 and reverse transcription-polymerase chain reaction( RT-PCR) was used to analyze the expression of TNF-α,iNOS,ICAM-1 mRNA.[Results]Compared with the normal control group,the model group's BP level was significantly increased( P <0. 01)),but the MGF had no significant lowering BP effect( P > 0. 05); compared with the normal control group,the expression of TNF-α,iNOS,ICAM-1 and its' mRNA in the model group was significantly increased( P < 0. 05 or P < 0. 01),and MGF could reduce the level of expression of these inflammatory cytokines( P < 0. 05 or P < 0. 01); between the Benazepril group and high-dose,medium-dose,low-dose MGF groups,most of the indicators had no significant difference( P > 0. 05). [Conclusions]MGF had no significant lowering BP effect,SHR showed inflammatory injury in the heart,brain and kidneys,MGF showed improvement on the inflammatory injury,and the anti-inflammation mechanism may be associated with lowering TNF-α,i NOS and ICAM-1 and its mRNA expression.

In vitro Pharmacological Activity of Chromenes in Disk of Helianthus annuus

[Objectives]The anti-tumor,anti-bacterial,anti-acetylcholinesterase and anti-α-glucosidase activity in vitro of five chromenes isolated from Helianthus annuus disk was studied,in order to provide reference for the development and utilization of H.annuus disk resources.[Methods]The effect of different concentrations of chromenes on the survival rate of leukemia HL-60 cells,lung cancer A549 cells,liver cancer SMMC-7721 cells,breast cancer MCF-7 cells and colon cancer SW480 cells was detected by MTS method,and the IC50 was calculated.The inhibitory activity of chromenes against Escherichia coli,Staphylococcus aureus subsp.aureus,Salmonella enterica subsp.enterica,Pseudomonas aeruginosa and Candida albicans was detected by microdilution method.The DTNB substrate method was used to detect the inhibitory activity of chromenes on acetylcholine.The PNPG substrate method was used to detect the inhibitory activity of chromenes onα-glucosidase.[Results]The five chromenes had no obvious in vitro inhibitory activity on the five kinds of tumor cells,with IC50 greater than 40μM.The five chromenes had no obvious in vitro inhibitory activity against the four kinds of bacteria and C.albicans.The five chromenes had certain inhibitory activity on acetylcholinesterase,and among them,6-acetyl-2,2-dimethylchromene and 6-acetyl-7-hydroxy-2,3-dimethylchromene showed strong inhibitory activity on acetylcholinesterase,with IC50 of 28.253 and 16.945μM,respectively,both smaller than that(0.275μM)of the positive control tacrine(P<0.01).The five chromenes showed good inhibitory effect onα-glucosidase,and among them,7-hydroxy-6-hydroxyacetyl-2,2-dimethylchromene and 6-acetyl-7-hydroxy-2,3-dimethylchromene had stronger inhibitory activity,with IC50 of 20.240 and 21.052μM,respectively,significantly better than that(169.780μM)of the positive control acarbose(P<0.01).[Conclusions]The five chromenes in H.annuus disk have certain in vitro inhibitory activity against acetylcholinesterase andα-glucosidase and certain potential in fighting neurodegenerative diseases and diabetes.

Mangiferin alleviates renal infammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway

Objective: Hypertension is a low-grade infammation state of the disease and was easily complicated by kidneys’ infammatory response. Mangiferin(MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-infammatory activity. However, the effects of MGF on renal infammatory injury in spontaneously hypertensive rats(SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal infammatory injury in SHRs.Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological,immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR(RT-PCR) analysis.Results: The results showed that the levels of interleukin 6(IL-6), tumor necrosis factor-a(TNF-a), monocyte chemoattractant protein-1(MCP-1) and recombinant chemokine C-C-Motif receptor 2(CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-a, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen(BUN) and serum uric acid(SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels.Conclusion: Our study proved that the kidneys of SHRs had significant infammatory injury, and MGF had the protective effects on renal infammatory injury in SHRs;The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

芒果苷通过抑制MCP-1/CCR2信号通路减轻自发性高血压大鼠心脏炎症损伤

高血压是一种低度炎症状态的疾病,通常伴有心脏炎症。芒果苷(MGF)是一种天然糖基蒽酮,具有很强的抗炎活性。然而,MGF对高血压患者心脏炎症损伤的作用尚不清楚。本文研究MGF对自发性高血压大鼠(SHRs)心脏炎症损伤的保护作用及其机制。采用10周龄雄性SHRs和10周龄正常雄性Wistar-Kyoto(WKY)大鼠,对SHRs使用10、20、40 mg/kg剂量的MGF,连续8周。测量其收缩压(SBP)水平,采集心脏组织进行形态学、免疫组化、ELISA、western blot和实时反转录PCR分析。结果表明模型组大鼠收缩压水平均较对照组显著升高,SHRs自发升高收缩压水平,各剂量MGF对收缩压水平无显著影响。模型组大鼠心脏组织形态学结果显示有明显的炎症性损伤,MGF对这种损伤有显著的抑制作用。同时,MGF显著抑制了SHRs IL-6和TNF-α含量的升高。此外,MGF还显著抑制了SHRs MCP-1、CCR2蛋白以及其mRNA表达的增加。研究表明MGF并不会降低SHRs大鼠的SBP水平,但MGF对SHRs大鼠的心脏炎症损伤具有保护作用,这可能是因为MGF部分抑制了MCP-1/CCR2信号通路表达的原因。

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric(Curcumae Rhizoma,Ezhu in Chinese)has a long history of application and has great potential in the treatment of liver cancer.The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances.In order to clarify the specific mechanism of zedoary tumeric against liver cancer,this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer,and then verifies the joint anti liver cancer mechanism of its“pharmacodynamic group”.By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years,we found that pharmacodynamic substances,including curcumol,zedoarondiol,curcumenol,curzerenone,curdione,curcumin,germacrone,β-elemene,can act on multi-target and multi-channel to play an antihepatoma role.For example,curcumin can regulate miR,GLO1,CD133,VEGF,YAP,LIN28B,GPR81,HCAR-1,P53 and PI3K/Akt/mTOR,HSP70/TLR4 and NF-κB.Wnt/TGF/EMT,Nrf2/Keap1,JAK/STAT and other pathways play an antihepatoma role.Network pharmacological analysis showed that the core targets of the“pharmacodynamic group”for anti-life cancer are AKT1,EGFR,MAPK8,etc,and the core pathways are neuroactive live receiver interaction,nitrogen metabolism,HIF-1 signaling pathway,etc.At the same time,by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and“pharmacodynamic group”,it is found that they have great reference significance in target,pathway,biological function,determination of core pharmacodynamic components,formation of core target protein interaction,in-depth research of single pharmacodynamic substance,increasing curative effect and so on.By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and“pharmacodynamic group”in the treatment of liver cancer,this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and“pharmacodynamic group”.

Screening and evaluation of antioxidants from lees by micro-injector systems combined with a fluorescent probe,N-borylbenzyloxycarbonyl-3,7-dihydroxyphenoxazine,in living Drosophila

Over the past few decades, the determination of antioxidant activity by chemical probe has been widely reported, but in vivo evaluation via model organisms of Drosophila melanogaster and rapid discovery system has not been studied adequately. In this study, we determined the antioxidant activity of lees and demonstrated the ability of compounds in lees to scavenge H_2O_2 in vitro and in vivo by different chemical probes. Lees increased the ability of Drosophila against oxidative stress and antioxidant enzyme activity in vivo. Five ingredients of organic acids and flavones in lees extract that rapidly scavenged H_2O_2 were revealed by a post-column-derived HPLC-UV-FLD system based on 4-hydroxyphenylacetic acid(PHPAA)chemiluminescence. Additionally, another fluorescent probe,N-borylbenzyloxycarbonyl-3,7-dihydroxyphenoxazine(NBCD), was selected to evaluate the reactive oxygen species(ROS) scavenging capacity of lees in living Drosophila melanogaster using a microfluidic injection test coupled with microscopic imaging analysis, and similar effects were observed in flies when they were treated with tartaric acid and caffeic acid. The results demonstrated that the novel integrated system was suitable for screening and evaluating antioxidant ingredients from natural products.