Physalins with anti-inflammatory activity are present in Physalis alkekengi var. franchetii and can function as Michael reaction acceptors

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• 作者：Long Ji^a ; Yonglei Yuan^a ; Liping Luo^a ; Zhe Chen^d ; Xiaoqiong Ma^d ; Zhongjun Ma^a ; ^b ; ^{mazj@zju.edu.cn} ; Lin Cheng^c
• 关键词：Physalins ; Michael reaction acceptors ; UPLC-ESI-MS/MS analysis ; Glutathione ; I魏B kinase 尾 ; Anti-inflammation
• 刊名：Steroids
• 出版年：2012
• 期刊代码：142_0039128x
• 类别：bio
• 出版时间：April, 2012
• 卷：77
• 期：5
• 页码：441-447
• 文件大小：893 K

摘要

Michael reaction acceptors (MRAs) are a class of active molecules that are directly or indirectly involved in various cellular processes, including the regulation of many signaling pathways. In this study, the inducible nitric oxide synthase (iNOS) assay was used to demonstrate that the dichloromethane extract of Physalis alkekengi var. franchetii (DCEP) possesses anti-inflammatory activity that might be attributed to the modification of key cysteine residues in IKK尾 by the MRAs in DCEP. To isolate these MRAs, glutathione (GSH) was employed, and a simple ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) screening method was developed to investigate the GSH conjugates with potential MRAs. Five physalins, including one new compound isophysalin A (2), together with four known steroidal compounds, physalin A (1), physalin O (3), physalin L (4) and physalin G (5), were isolated to evaluate the GSH conjugating abilities, and it was indicated that compounds 1, 2 and 3, which had a common 伪,尾-unsaturated ketone moiety, exhibited conjugating abilities with GSH and also showed significant nitric oxide (NO) production inhibiting activities. The anti-inflammatory activities of compounds 1, 2 and 3 might be attributed to their targeting multiple cysteine residues on IKK尾; therefore, the alkylation of IKK尾 by compound 1 was further studied by micrOTOF-MS. The result showed that six cysteine residues (C₅₉, C₁₇₉, C₂₉₉, C₃₇₀, C₄₁₂, and C₆₁₈) were alkylated, which indicated that IKK尾 is a potential target for the anti-inflammatory activity of physalin A.