Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway.
10.1016/S1875-5364(21)60110-3
- Author:
Shu-Ping CHEN
1
;
Tian-Hong HU
2
;
Qing ZHOU
2
;
Tian-Peng CHEN
2
;
Dong YIN
3
;
Huan HE
4
;
Qing HUANG
5
;
Ming HE
6
,
7
Author Information
1. Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
2. Jiangxi Provincial Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, China.
3. Jiangxi Provincial Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
4. Jiangxi Provincial Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, China. Electronic address: hehuan0118@ncu.edu.cn.
5. Jiangxi Provincial Institute of Cardiovascular Diseases, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang 330006, China. Electronic address: hg6897700@163.com.
6. Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China
7. Jiangxi Provincial Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, China.
- Publication Type:Journal Article
- Keywords:
Endothelium dysfunction;
Iron overload;
Luteoloside;
Mitochondria;
ROS/ADMA/ DDAH II/eNOS/NO pathway
- MeSH:
Endothelium, Vascular;
Glucosides;
Humans;
Iron Overload;
Luteolin;
Reactive Oxygen Species
- From:
Chinese Journal of Natural Medicines (English Ed.)
2022;20(1):22-32
- CountryChina
- Language:English
-
Abstract:
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. Lonicera japonica 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 viability and weakened LDH activity, but also significantly up-regulated DDAHⅡ expression and activity, increased p-eNOS/eNOS ratio and NO content, and reduced ADMA content in HUVECs exposed to iron overload. Furthermore, Lut significantly attenuated intracellular/mitochondrial ROS generation, improved SOD, CAT, and GSH-Px activities, reduced MDA content, maintained MMP, inhibited 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 substrate), 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 effects.
