NP-22 Dihydrotanshinone I,A Natural Product,Exhibits Anti-Inflammatory Effects through Blocking TLR4 Dimerization

Objective:Dihydrotanshinone I(DHT)is a natural product with multiple bioactivities.In this study,we aimed to investigate its anti-infl ammatory effect and potential mechanisms.Methods and Results:Lipopolysaccharide(LPS)was used to induce acute kidney injury(AKI)in mice and establish infl ammation in macrophage.In vivo experiment,pretreatment of mice with DHT effectively inhibited xylene-induced ear oedema and LPS-induced endotoxic death and protected against LPSinduced AKI.DHT suppressed COX-2,iNOS,TNF-α,IL-6 and IL-1βexpression.In vitro experiment,DHT attenuated LPS-induced transcriptional activity of NF-κB by decreasing levels of phosphorylated IκB-αand IKK and NF-κB/p65 nuclear translocation.In addition,DHT blocked LPS-induced TLR4 dimerization,resulting in the recruiting of MyD88 and TRIF.Conclusion:In summary,DHT blocks TLR4 dimerization to activate MyD88-TAK1-NF-Κb signalling cascades and TRIF pathway.Our data indicated that DHT is a potential lead compound for treatment of infl ammatory diseases.

胶原蛋白肽经由HO-1途径保护H_2O_2诱导的MC3T3-E1细胞损伤

目的骨质疏松症与氧化应激和活性氧(ROS)的产生密切相关,胶原蛋白肽具有潜在的抗氧化作用,其作用机理尚不清楚,因此,本研究在胶原蛋白肽对过氧化氢(H_2O_2)诱导的MC3T3-E1小鼠前成骨细胞氧化应激的保护作用的基础上,探讨其分子作用机制。方法实验分为正常组,H_2O_2组,胶原蛋白肽低、中、高剂量组(10、100、500g·L^(-1))。胶原蛋白肽各组加入相应浓度的药物预处理24h后,与H_2O_2组一起加入400μmol·L^(-1) H_2O_2孵育24h,空白对照组正常培养。CCK 8和乳酸脱氢酶(LDH)的释放检测细胞毒性。抗氧化试剂盒检测细胞内活性氧(ROS)、谷胱甘肽过氧化物酶(GSH)和丙二醛(MDA)含量的变化,Western blot和RT-PCR分别检测细胞内HO-1蛋白及mRNA的表达水平。结果胶原蛋白肽能够上调H_2O_2诱导的细胞存活率,以剂量依赖的方式显著降低H_2O_2诱导的氧化损伤。胶原蛋白肽能够及时清除细胞内的活性氧,显著上调HO-1的基因表达,提高GSH、MDA的活性,减轻脂质过氧化反应。结论胶原蛋白肽通过激活HO-1基因表达水平,提高抗氧化活性,对H_2O_2诱导MC3T3-E1细胞的氧化损伤发挥保护作用。