Luteolin could be a promising candidate molecule for atherosclerosis. - GreenMedInfo Summary
Luteolin Attenuates Atherosclerosis Via Modulating Signal Transducer And Activator Of Transcription 3-Mediated Inflammatory Response.
Drug Des Devel Ther. 2019 ;13:3899-3911. Epub 2019 Nov 18. PMID: 31819365
Background: Inflammatory factors play a crucial role throughout the development and progression of atherosclerosis, which has been considered as a chronic vascular inflammatory disease. Luteolin, a natural flavonoid which exists in many natural medicinal materials, has anti-inflammatory, anti-fibrotic and other pharmacological effects. Recently, the protective effects of luteolin on the cardiovascular disease have been reported. However, there is a paucity of studies on anti-atherosclerosis. Therefore, the anti-atherosclerosis potential of luteolin remains to be elucidated.
Method: ApoEmice were fed with a high-fat diet to induce atherosclerosis in an animal model, where they were treated with oral administration of luteolin for 12 weeks. Primary mouse peritoneal macrophages challenged with oxidized low-density lipoprotein (oxLDL) were used for in vitro mechanistic study. The effectiveness of luteolin in the ApoEmouse model of atherosclerosis was estimated in the aortic sinus and enface, and the underlying mechanisms were explored by molecular modeling study and siRNA-induced gene silencing.
Results: Our results showed that luteolin remarkably attenuated atherosclerosis in high-fat diet-induced ApoEmouse via alleviating inflammation. We further found that luteolin decreased oxLDL-induced inflammation by inhibiting signal transducer and activator of transcription 3 (STAT3) in vitro, respectively. Further molecular modeling analysis indicated that luteolin interacted with STAT3 primarily through hydrogen bond interaction.
Conclusion: Luteolin could be a promising candidate molecule for atherosclerosis, and STAT3 may be a potential therapeutic target that could prevent the development of atherosclerosis.