Ergosta-7, 9 (11), 22-trien-3β-ol Interferes with LPS Docking to LBP, CD14, and TLR4/MD-2 Co-Receptors to Attenuate the NF-κB Inflammatory Pathway In Vitro and Drosophila

被引：12

作者：

Hsieh, Wen-Tsong ^{[1
,2
]}

Hsu, Min-Hsien ^{[3
]}

Lin, Wen-Jen ^{[4
]}

Xiao, Yi-Cheng ^{[5
]}

Lyu, Ping-Chiang ^{[6
]}

Liu, Yi-Chung ^{[7
]}

Lin, Wei-Yong ^{[8
]}

Kuo, Yueh-Hsiung ^{[2
,9
]}

Chung, Jing-Gung ^{[10
]}

机构：

[1] China Med Univ, Dept Pharmacol, Taichung 40402, Taiwan

[2] China Med Univ, Chinese Med Res Ctr, Taichung 40402, Taiwan

[3] Chang Bing Show Chwan Mem Hosp, Dept Neurol, Changhua 505, Taiwan

[4] China Med Univ, Grad Inst Biomed Sci, Taichung 40402, Taiwan

[5] Natl Cheng Kung Univ, Coll Med, Sch Med, Tainan 701, Taiwan

[6] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, Hsinchu 300044, Taiwan

[7] Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli 350, Taiwan

[8] China Med Univ, Coll Chinese Med, Grad Inst Integrated Med, Taichung 40402, Taiwan

[9] China Med Univ, Dept Chinese Pharmaceut Sci & Chinese Med Resourc, Taichung 40402, Taiwan

[10] China Med Univ, Dept Biol Sci & Technol, Taichung 40402, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 12期

关键词：

Ergosta-7; 9 (11); 22-trien-3 beta-ol (EK100); LPS; LBP; CD14; TLR4/MD-2; NF-kappa B; Drosophila; CHEMOKINE GENE-EXPRESSION; ANTRODIA-CAMPHORATA; CRYSTAL-STRUCTURE; NITRIC-OXIDE; KINASE; RESPONSES; ACTIVATION; CYTOKINE; MAPK; ERGOSTATRIEN-3-BETA-OL;

D O I：

10.3390/ijms22126511

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ergosta-7, 9 (11), 22-trien-3 beta-ol (EK100) was isolated from Cordyceps militaris, which has been used as a traditional anti-inflammatory medicine. EK100 has been reported to attenuate inflammatory diseases, but its anti-inflammatory mechanism is still unclear. We were the first to investigate the effect of EK100 on the Toll-like receptor 4 (TLR4)/nuclear factor of the kappa light chain enhancer of B cells (NF-kappa B) signaling in the lipopolysaccharide (LPS)-stimulated RAW264.7 cells and the green fluorescent protein (GFP)-labeled NF-kappa B reporter gene of Drosophila. EK100 suppressed the release of the cytokine and attenuated the mRNA and protein expression of pro-inflammatory mediators. EK100 inhibited the inhibitor kappa B (I kappa B)/NF-kappa B signaling pathway. EK100 also inhibited phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt) signal transduction. Moreover, EK100 interfered with LPS docking to the LPS-binding protein (LBP), transferred to the cluster of differentiation 14 (CD14), and bonded to TLR4/myeloid differentiation-2 (MD-2) co-receptors. Compared with the TLR4 antagonist, resatorvid (CLI-095), and dexamethasone (Dexa), EK100 suppressed the TLR4/AKT signaling pathway. In addition, we also confirmed that EK100 attenuated the GFP-labeled NF-kappa B reporter gene expression in Drosophila. In summary, EK100 might alter LPS docking to LBP, CD14, and TLR4/MD-2 co-receptors, and then it suppresses the TLR4/NF-kappa B inflammatory pathway in LPS-stimulated RAW264.7 cells and Drosophila.

引用

页数：19