Gastrodin ameliorates atherosclerosis by inhibiting foam cells formation and inflammation through down-regulating NF-κB pathway

Xiaofei Xue; Fulei Li; Mengke Xu; Bowen Chen; Yanyan Zhao; Mengyu Wang; Ling Li

doi:10.1186/s12986-022-00722-z

Gastrodin ameliorates atherosclerosis by inhibiting foam cells formation and inflammation through down-regulating NF-κB pathway

Nutr Metab (Lond). 2023 Feb 9;20(1):9. doi: 10.1186/s12986-022-00722-z.

Authors

Xiaofei Xue¹, Fulei Li², Mengke Xu³, Bowen Chen³, Yanyan Zhao³, Mengyu Wang³, Ling Li⁴

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. fccxuexf@zzu.edu.cn.
² Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
⁴ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. liling60035@sina.com.

Abstract

Background: Gastrodin is an effective polyphenol extracted from Chinese natural herbal Gastrodiae elata Blume, which exhibits antioxidant and anti-inflammatory effects. It has been reported to benefit neurodegenerative diseases, but the effect of Gastrodin on atherosclerosis and the underlying mechanisms remain elusive. The aim of this study is to investigate the function and mechanism of Gastrodin in atherosclerosis.

Methods: Atherosclerosis mouse model was established by fed low density lipoprotein receptor-deficient (Ldlr^-/-) mice with a high fat diet (HFD, 20% fat and 0.5 cholesterol) for 8 weeks and Gastrodin was administered daily via oral gavage. Plasma lipid levels were measured using commercial kits. En face and aortic sinus lipid accumulation were analyzed with Oil Red O staining. In vitro cell models using foam cell formation model and classical atherosclerosis inflammation model, macrophages were incubated with oxygenized low-density lipoproteins (ox-LDL) or lipopolysaccharide (LPS) in the presence of different concentration of Gastrodin or vehicle solution. Foam cell formation and cellular lipid content were evaluated by Oil Red O staining and intracellular lipids extraction analysis. Gene expression and proteins related to cholesterol influx and efflux were examined by quantitative reverse transcription PCR (RT-qPCR) and western blotting analysis. Furthermore, the effect of Gastrodin on LPS induced macrophage inflammatory responses and NF-κB pathway were evaluated by RT-qPCR and western blotting analysis.

Results: Gastrodin administration reduced the body weight, plasma lipid levels in Ldlr^-/- mice after fed a high fat diet. Oil Red O staining showed Gastrodin-treated mice displayed less atherosclerosis lesion area. Furthermore, Gastrodin treatment significantly ameliorated ox-LDL-induced macrophage-derived foam cells formation through suppressing genes expression related to cholesterol efflux including scavenger receptor class B and ATP-binding cassette transporter A1. Moreover, Gastrodin markedly suppressed pro-inflammatory cytokines secretion and LPS induced inflammatory response in macrophage through downregulating NF-κB pathway.

Conclusions: Our study demonstrated that Gastrodin attenuates atherosclerosis by suppressing foam cells formation and LPS-induced inflammatory response and represents a novel therapeutic target for the treatment of atherosclerosis.

Keywords: Atherosclerosis; Foam cell formation; Gastrodin; Inflammation; Macrophage.