Quinone Reductase (QR) Inducers From Andrographis Paniculata And Identification Of Molecular Targets Of Andrographolide

In the present study, it was demonstrated that the petroleum extract of Andrographis paniculata (APPE) had quinone reductase (QR) inducing activity, which might be attributed by the Michael addition acceptors (MAAs) in it. To screen MAAs in APPE, glutathione (GSH) was employed, and a LC/MS method was implied. Three compounds, andrographoside, andrographolide, and14-deoxy-14,15-dehydroandrographolide were revealed could well conjugated with GSH. Then, andrographolide along with4new and14known compounds were isolated to conduct QR induction evaluation, and the CD (the concentration required to double the activity of QR) value of andrographolide is1.43μM while the other copounds showed inactive, verifying the reliability of the method LC-MS for revealing compounds with QR induction activities.The QR induce activity of andrographolide might be attributed to its targeting multiple cysteine residues in Keap1, therefore, the alkylation of Keapl by andrographolide was further studied and the result showed that four cysteine residues: Cys77, Cys151, Cys273and Cys368were alkylated, which indicated that Keapl is a potential target for the QR induce activity of andrographolide.