Drug Design, Development and Therapy (2019-11-01)

Luteolin Attenuates Atherosclerosis Via Modulating Signal Transducer And Activator Of Transcription 3-Mediated Inflammatory Response

  • Ding X,
  • Zheng L,
  • Yang B,
  • Wang X,
  • Ying Y

Journal volume & issue
Vol. Volume 13
pp. 3899 – 3911

Abstract

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Xiaoji Ding,1,* Lulu Zheng,1,* Bo Yang,1,* Xiaodong Wang,2 Yin Ying1 1Department of Pharmacy, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, People’s Republic of China; 2Department of Vascular Surgery, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yin YingDepartment of Pharmacy, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou 310012, Zhejiang, People’s Republic of ChinaTel +86-571-89972240Email [email protected]: 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: ApoE-/- mice 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 ApoE-/- mouse 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 ApoE-/- mouse 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.Keywords: atherosclerosis, luteolin, inflammation, transducer and activator of transcription 3

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