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Targeting inflammation‐associated AMPK //Mfn‐2/ MAPKs signaling pathways by baicalein exerts anti‐atherosclerotic action
Author(s) -
Zhang Xinxin,
Qin Yating,
Ruan Weibin,
Wan Xiaoning,
lv Chao,
He Lin,
Lu Li,
Guo Xiaomei
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.7149
Subject(s) - baicalein , ampk , inflammation , pharmacology , chemistry , proinflammatory cytokine , signal transduction , p38 mitogen activated protein kinases , phosphorylation , tumor necrosis factor alpha , mapk/erk pathway , microbiology and biotechnology , biochemistry , medicine , endocrinology , biology , protein kinase a
Inflammatory responses in macrophages, endothelial cells, and vascular smooth muscle cells play crucial roles in the development of atherosclerosis. Baicalein, a flavonoid phytochemical, possesses anti‐inflammatory properties, but the underlying mechanisms of its action are not fully understood. The aim of this study was to explore whether baicalein inhibited inflammatory activities in RAW264.7, HUVEC, and MOVAS cells and to analyze its underlying mechanisms. Our results showed that baicalein treatment effectively reduced the levels of IL‐6, TNF‐α, PAI‐1, and MMP‐9 released by these cells upon stimulation with Ang II or ox‐LDL. We discovered that the molecular mechanisms underlying baicalein suppression of the generation of proinflammatory cytokines were associated with the inhibition of MAPK/NF‐κB pathway activity. Moreover, Ang II and ox‐LDL intervention decreased the content of Mfn‐2 in the three types of cells, but incubation of baicalein alleviated the Ang II/ox‐LDL‐induced reduction of Mfn‐2 levels. Adv‐Mfn2 treatment not only increased the expression of Mfn‐2 but also reduced the levels of phosphorylated ERK1/2, p38, JNK, and NF‐κB, followed by a decrease in the concentrations of IL‐6, TNF‐α, PAI‐1, and MMP‐9 in the supernatant. Furthermore, our findings indicated that baicalein treatment markedly suppressed the decrease in AMPK activity induced with Ang II and ox‐LDL, and incubation with Compound C reversed the effects of baicalein on AMPK activation and Mfn‐2 expression. In conclusion, our data suggest that baicalein shows anti‐inflammatory properties, probably by activating the AMPK/Mfn‐2 axis, accompanied by inhibition of downstream MAPKs/NF‐κB signaling transduction.