C21-steroidal pregnane sapogenins and their derivatives as anti-inflammatory agents

被引：15

作者：

Huang, Lie-Jun ^{[1
,4
]}

Chen, Shao-Ru ^{[2
,3
]}

Yuan, Chun-Mao ^{[1
]}

Gu, Wei ^{[1
]}

Guo, Bao-Jian ^{[2
,3
]}

Wang, Yi-Tao ^{[2
,3
]}

Wang, Ying ^{[2
,3
]}

Hao, Xiao-Jiang ^{[1
]}

机构：

[1] State Key Lab Funct & Applicat Med Plants, Guiyang 550002, Peoples R China

[2] Univ Macau, State Key Lab Qual Res Chinese Med, Ave uNIV, Taipa, Macao, Peoples R China

[3] Univ Macau, Inst Chinese Med Sci, Ave uNIV, Taipa, Macao, Peoples R China

[4] Guizhou Univ, Ctr Res & Dev Fine Chem, Guiyang 550025, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 13期

关键词：

C21-steroidal pregnane steroids; Anti-inflammation; TLR; NF-kappa B; TRAF6; ALPHA;

D O I：

10.1016/j.bmc.2017.04.045

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：

During the screening of natural anti-inflammatory agent, we identified some C21-steroidal pregnane sapogenins or the derivatives to inhibit TLR2, TLR3, and TLR4-initiated inflammatory responses respectively. Treatment with active compounds 10, 2j and 3p failed to impact tumor necrosis factor-ot (TNF-a) induced nucleus translocation of NF-kappa B p65 subunit. However, these compounds regulated distinct canonical or non-canonical NF-kappa B family members. Ectopic expression of TNF receptor associated factor 6 (TRAF6) abrogated the inhibitory activity of the compounds on production of pro-inflammatory cytokines downstream of TLR4. These results suggested that compounds 10, 2j, and 3p suppressed TLRinitiated innate immunity through TRAF6 with differential regulation of NF-KB family proteins. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：3512 / 3524

页数：13

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