摘要
目的 观察纳米制姜黄素(PURCUMIN?)与普通姜黄素(Curcumin 95%)的体内药物代谢动力学特征及体外抗炎作用。方法 分别灌胃给予200 mg/kg的PURCUMIN?和Curcumin 95%,观察两者在SD大鼠体内的药物代谢动力学参数,并计算相对生物利用度以评价PURCUMIN?的制剂优势。利用肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)刺激人脐静脉内皮细胞,在体外模拟炎症诱导的内皮细胞损伤模型。以关键炎症因子水平、关键炎症因子的基因表达水平及核因子-κB抑制蛋白(inhibitor of nuclear factor-κB,IκB)/核因子-κB(nuclear factor-κB,NF-κB)信号通路中关键蛋白的表达水平,评价两种姜黄素制剂在不同给药浓度和不同作用时间下对内皮细胞的保护作用。结果 在相同给药剂量(200 mg/kg)下,PURCUMIN?相较于Curcumin 95%在大鼠体内的暴露量增加了17.5倍。姜黄素能有效抑制TNF-α刺激引起的内皮细胞炎症,且PURCUMIN?的抗炎效果更为显著。在相同干预时间下,低浓度(1μmol/L)的PURCUMIN?即可显著降低细胞培养上清中前列腺素E2、白细胞介素-1β、白细胞介素-6、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)的水平(P<0.05),抑制环氧合酶-2、MCP-1 mRNA表达(P<0.05),抑制IκB/NF-κB信号通路的激活(P<0.05),其药理作用与高浓度(10μmol/L)Curcumin 95%相当;在相同干预浓度下,PURCUMIN?在2 h时即可显著降低上述炎症因子水平,抑制IκB/NF-κB信号通路激活(P<0.05),其药理作用与Curcumin 95%干预4 h时相当。结论 PURCUMIN?在较低浓度、较短时间即可发挥较好的抗炎作用,这可能与其显著提升的生物利用度有关。
Objective To investigate the in vivo pharmacokinetics and in vitro anti-inflammatory effect of nano-formulatedcurcumin(PURCUMIN )versus ordinary curcumin(Curcumin 95%).Methods Sprague-Dawley rats were given PURCUMIN or Curcumin 95%by gavage at a dose of 200 mg/kg to observe their pharmacokinetic parameters in vivo,and relative bioavailability was calculated to evaluate the advantages of PURCUMIN .Human umbilical vein endothelial cells(HUVECs)were stimulated with tumor necrosis factor-α(TNF-α)to establish a model of inflammation-induced endothelial cell injury.The two curcumin preparations were compared in terms of their protective effect on endothelial cells at different concentrations and durations of action based on the levels of key inflammatory factors and the expression levels of the key proteins in the inhibitor of nuclear factor-κB(IκB)/nuclear factor-kappa B(NF-κB)signaling pathway.Results At the same dose of 200 mg/kg,the exposure of PURCUMIN in rats was significantly increased by 17.5 times compared with that of Curcumin 95%.Curcumin effectively inhibited the inflammation of endothelial cells induced by TNF-α,and PURCUMIN had a significantly better anti-inflammatory effect.Under the same duration of intervention,low-concentration PURCUMIN significantly reduced the levels of prostaglandin E 2,interleukin-1β,interleukin-6,and monocyte chemoattractant protein-1(MCP-1)(P<0.05)and inhibited the mRNA expression of cyclooxygenase-2 and MCP-1(P<0.05)and the activation of the IκB/NF-κB signaling pathway(P<0.05),with a comparable pharmacological action to high-concentration Curcumin 95%(10μmol/L).Under the same concentration of intervention,PURCUMIN significantly reduced the levels of the above inflammatory factors and inhibited the activation of the IκB/NF-κB signaling pathway within 2 hours(P<0.05),with a comparable pharmacological action to Curcumin 95%intervention for 4 hours.Conclusion PURCUMIN can exert a good anti-inflammatory effect at a relatively low concentration and within a short period of time,which might be associated with its significantly improved bioavailability.
作者
何飞燕
陈欢
邱志霞
金子恒
齐淑贞
黄芳
HE Feiyan;CHEN Huan;QIU Zhixia;JIN Ziheng;QI Shuzhen;HUANG Fang(School of Chinese Materia Medica,China Pharmaceutical University,Jiangsu Nanjing 211198,China;Henan ZhongdaHengyuan Biotechnology Stock Co.,Ltd.,Henan Luohe 462600,China;Institute of Dermatology,Chinese Academy of Medical Sciences,Jiangsu Nanjing 210042,China)
出处
《安徽中医药大学学报》
CAS
2024年第1期81-88,共8页
Journal of Anhui University of Chinese Medicine
关键词
生物利用度
姜黄素
炎症
人脐静脉内皮细胞
核因子-ΚB
Bioavailability
Curcumin
Inflammation
Human umbilical vein endothelial cells
Nuclear factor-kappa B
