BACKGROUND:Paraquat(PQ)-induced acute lung injury(ALI)and pulmonary fi brosis are common diseases with high mortality but without eff ective antidotes in emergency medicine.Our previous study has proved that arctigeni...BACKGROUND:Paraquat(PQ)-induced acute lung injury(ALI)and pulmonary fi brosis are common diseases with high mortality but without eff ective antidotes in emergency medicine.Our previous study has proved that arctigenin suppressed pulmonary fibrosis induced by PQ.We wondered whether arctigenin could also have a protective eff ect on PQ-induced ALI.METHODS:A PQ-induced A549 cell injury model was used,and the effect of arctigenin was determined by a cell counting kit-8(CCK-8)cell viability assay.In addition,terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labelling(TUNEL)staining assays and mitochondrial membrane potential assays were performed to evaluate the level of cell apoptosis.The generation of reactive oxygen species(ROS)was refl ected by dihydroethidium(DHE)staining and a 2’,7’-dichlorodihy drofluorescein diacetate(DCFH-DA)assay.Moreover,immunoblotting studies were used to assess the expression of mitogen-activated protein kinases(MAPKs)and p38 MAPK.RESULTS:Arctigenin attenuated PQ-induced inhibition of A549 cell viability in a dose-dependent manner.Arctigenin also significantly reduced PQ-induced A549 cell apoptosis,as refl ected by the TUNEL assay and mitochondrial membrane potential assay,which may result from suppressed ROS/p38 MAPK signaling because we found that arctigenin dramatically suppressed ROS generation and p38 MAPK phosphorylation.CONCLUSION:Arctigenin could attenuate PQ-induced lung epithelial A549 cell injury in vitro by suppressing ROS/p38 MAPK-mediated cell apoptosis,and arctigenin might be considered a potential candidate drug for PQ-induced ALI.展开更多
Acute inflammation is a central component in the progression of spinal cord injury(SCI).Anti-inflammatory drugs used in the clinic are often administered systemically at high doses,which can paradoxically increase inf...Acute inflammation is a central component in the progression of spinal cord injury(SCI).Anti-inflammatory drugs used in the clinic are often administered systemically at high doses,which can paradoxically increase inflammation and result in drug toxicity.A cluster-like mesoporous silica/arctigenin/CAQK composite(MSN-FC@ARCG)drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord.In this nanosystem,mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites.The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood–brain barrier.Arctigenin,a Chinese herbal medicine,was loaded into the nanosystem to reduce inflammation.The in vivo results showed that MSN-FC@ARC-G could attenuate inflammation at the injury site.Behavior and morphology experiments suggested that MSN-FC@ARC-G could diminish local microenvironment damage,especially reducing the expression of interleukin-17(IL-17) and IL-17-related inflammatory factors,inhibiting the activation of astrocytes,thus protecting neurons and accelerating the recovery of SCI.Our study demonstrated that this novel,silica-based drug delivery system has promising potential for clinical application in SCI therapy.展开更多
基金This work was supported by the National Natural Science Foundation of China(82172182 and 82102311)Social Development Projects of Jiangsu Province(BE2017720)+2 种基金Natural Science Foundation of Jiangsu Province(BK20190247)Science Foundation of Jiangsu Health Commission(H2018039)Jiangsu Postdoctoral Research Foundation(2018K048A and 2020Z193).
文摘BACKGROUND:Paraquat(PQ)-induced acute lung injury(ALI)and pulmonary fi brosis are common diseases with high mortality but without eff ective antidotes in emergency medicine.Our previous study has proved that arctigenin suppressed pulmonary fibrosis induced by PQ.We wondered whether arctigenin could also have a protective eff ect on PQ-induced ALI.METHODS:A PQ-induced A549 cell injury model was used,and the effect of arctigenin was determined by a cell counting kit-8(CCK-8)cell viability assay.In addition,terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labelling(TUNEL)staining assays and mitochondrial membrane potential assays were performed to evaluate the level of cell apoptosis.The generation of reactive oxygen species(ROS)was refl ected by dihydroethidium(DHE)staining and a 2’,7’-dichlorodihy drofluorescein diacetate(DCFH-DA)assay.Moreover,immunoblotting studies were used to assess the expression of mitogen-activated protein kinases(MAPKs)and p38 MAPK.RESULTS:Arctigenin attenuated PQ-induced inhibition of A549 cell viability in a dose-dependent manner.Arctigenin also significantly reduced PQ-induced A549 cell apoptosis,as refl ected by the TUNEL assay and mitochondrial membrane potential assay,which may result from suppressed ROS/p38 MAPK signaling because we found that arctigenin dramatically suppressed ROS generation and p38 MAPK phosphorylation.CONCLUSION:Arctigenin could attenuate PQ-induced lung epithelial A549 cell injury in vitro by suppressing ROS/p38 MAPK-mediated cell apoptosis,and arctigenin might be considered a potential candidate drug for PQ-induced ALI.
文摘目的 探究牛蒡子苷元(ATG)对慢性心力衰竭(CHF)大鼠心室重构和炎性反应的影响,并分析其潜在机制。方法 79只SD大鼠随机选取12只为假手术组,其余大鼠采用腹主动脉缩窄术建立CHF大鼠模型,成功造模60只大鼠随机分为CHF组、ATG低剂量组(ATG-L组,10 mg/kg)、ATG高剂量组(ATG-H组,20 mg/kg)、ATG+阴性对照(ATG+NC)组[20 mg/kg ATG+100μl高迁移率族蛋白B1(HMGB1)阴性对照质粒]、ATG+HMGB1组(20 mg/kg ATG+100μl HMGB1过表达质粒),每组12只。各组给予相应干预4周后,检测大鼠心功能、B型钠尿肽、N末端B型钠尿肽前体和炎性因子白细胞介素6、TNF-α水平、心脏质量指数和左心室质量指数、心肌组织病理变化、心肌细胞横截面积和心肌胶原体积分数、左心室心肌组织HMGB1/Toll样受体4(TLR4)/核转录因子κB(NF-κB)信号通路相关蛋白表达。结果 与假手术组比较,CHF组大鼠心肌组织HMGB1(0.42±0.05 vs 0.15±0.02)、TLR4(0.70±0.09 vs 0.21±0.04)蛋白水平和磷酸化NF-κB p65(p-NF-κB p65)/NF-κB p65(0.73±0.09 vs 0.26±0.05)蛋白比值显著升高,LVEF、左心室短轴缩短率(LVFS)显著降低(P<0.05);与CHF组比较,ATG-L组和ATG-H组大鼠心肌组织HMGB1(0.33±0.04、0.24±0.04 vs 0.42±0.05)、TLR4(0.56±0.06、0.41±0.05 vs 0.70±0.09)蛋白水平和p-NF-κB p65/NF-κB p65(0.61±0.08、0.49±0.06 vs 0.73±0.09)蛋白比值依次降低,LVEF、LVFS依次升高(P<0.05);HMGB1过表达能明显减弱ATG对HMGB1/TLR4/NF-κB信号通路和CHF大鼠心室重构、炎性反应的抑制作用(P<0.05)。结论 ATG可能通过抑制HMGB1/TLR4/NF-κB信号炎性通路,抑制了CHF大鼠的心室重构。
文摘建立了分离鉴定牛蒡叶中微量木脂体牛蒡子甙(arctiin)和牛蒡子甙元(arctigenin)的方法。牛蒡叶粗提物经聚酰胺柱提取,浓缩其甲醇洗脱液并于低温下静置析出白色沉淀物。沉淀物用甲醇溶解后经反相高效液相色谱(RP HPLC)分离,纯化得到两个主要组分。经紫外光谱(UV)、红外光谱(FTIR)及电喷雾质谱(ESI MS)检测,并与牛蒡子甙和牛蒡子甙元对照品的UV,LC ESI MS,HPLC及FTIR图谱比较,鉴定两个主要成分为牛蒡子甙和牛蒡子甙元。
基金supported by the National Natural Science Foundation of China(Nos.31670969,51302089,and 31571030)the Fundamental Research Funds for the Central Universities(No.21617428)+3 种基金Key Program of Traditional Chinese Medicine of Guangdong Province(No.20173018)The Science and Technology Program of Jiangmen City of China(No.2017A2004)Natural Science Foundation of Guangdong Province(No.2018A030313576)Science and Technology Program of Guangzhou(No.201803010001)
文摘Acute inflammation is a central component in the progression of spinal cord injury(SCI).Anti-inflammatory drugs used in the clinic are often administered systemically at high doses,which can paradoxically increase inflammation and result in drug toxicity.A cluster-like mesoporous silica/arctigenin/CAQK composite(MSN-FC@ARCG)drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord.In this nanosystem,mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites.The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood–brain barrier.Arctigenin,a Chinese herbal medicine,was loaded into the nanosystem to reduce inflammation.The in vivo results showed that MSN-FC@ARC-G could attenuate inflammation at the injury site.Behavior and morphology experiments suggested that MSN-FC@ARC-G could diminish local microenvironment damage,especially reducing the expression of interleukin-17(IL-17) and IL-17-related inflammatory factors,inhibiting the activation of astrocytes,thus protecting neurons and accelerating the recovery of SCI.Our study demonstrated that this novel,silica-based drug delivery system has promising potential for clinical application in SCI therapy.
