Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH Ⅱ/eNOS/NO pathway

• 作者: CHEN Shu-Ping HU Tian-Hong ZHOU Qing CHEN Tian-Peng YIN Dong HE Huan HUANG Qing HE Ming
• 来源期刊: 中国天然药物
• 学科: 医学
• 年，卷（期）: 2022,（1）
• 所属期刊栏目: Research articles
• 页码范围: 22-32
• 页数: 11页
• 分类号: R965
• 语种: 英文
• DOI: 10.1016/S1875-5364(21)60110-3

摘要

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine.Its primary therapies include clearing heat and detoxification,activating blood circulation,and removing blood stasis.Lonicerajapon-ica flos (LJF) has long been known as an excellent antipyretic and antidote.Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant,anti-inflammatory,and cytoprotective properties.However,the protection of Lut against iron overload injury and its underlying mechanisms remain unclear.Therefore,HUVECs were exposed to 50 μmol·L-1 iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed.Our results showed that 20 μmol·L-1 Lut not only increased cell vi-ability and weakened LDH activity,but also significantly up-regulated DDAH Ⅱ expression and activity,increased p-eNOS/eNOS ra-tio and NO content,and reduced ADMA content in HUVECs exposed to iron overload.Furthermore,Lut significantly attenuated intra-cellular/mitochondrial ROS generation,improved SOD,CAT,and GSH-Px activities,reduced MDA content,maintained MMP,inhib-ited mPTP opening,prevented cyt c from mitochondria released into cytoplasm,reduced cleaved-caspase3 expression,and ultimately decreased cell apoptosis induced by iron overload.The effects of Lut were similar to those of L-arginine (an ADMA competitive sub-strate),cyclosporin A (a mPTP blocker agent),and edaravone (a free radical scavenger) as positive controls.However,addition of pAD/DDAH Ⅱ-shRNA adenovirus reversed the above beneficial effects of Lut.In conclusion,Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAH Ⅱ/eNOS/NO pathway.The mitochondria are the target organelles of Lut's protective ef-fects.