Physalins with anti-inflammatory activity are present in Physalis alkekengi var. franchetii and can function as Michael reaction acceptors
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 IKKβ 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 α,β-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 IKKβ; therefore, the alkylation of IKKβ by compound 1 was further studied by micrOTOF-MS. The result showed that six cysteine residues (C 59 , C 179 , C 299 , C 370 , C 412 , and C 618 ) were alkylated, which indicated that IKKβ is a potential target for the anti-inflammatory activity of physalin A.
危险品化学品经营许可证（带存储）