In vivo induction of phase II detoxifying enzymes, glutathione transferase and quinone reductase by citrus triterpenoidsReport as inadecuate

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BMC Complementary and Alternative Medicine

, 10:51

First Online: 17 September 2010Received: 19 May 2010Accepted: 17 September 2010


BackgroundSeveral cell culture and animal studies demonstrated that citrus bioactive compounds have protective effects against certain types of cancer. Among several classes of citrus bioactive compounds, limonoids were reported to prevent different types of cancer. Furthermore, the structures of citrus limonoids were reported to influence the activity of phase II detoxifying enzymes. The purpose of the study was to evaluate how variations in the structures of citrus limonoids namely nomilin, deacetyl nomilin, and isoobacunoic acid and a mixture of limonoids would influence phase II enzyme activity in excised tissues from a mouse model.

MethodsIn the current study, defatted sour orange seed powder was extracted with ethyl acetate and subjected to silica gel chromatography. The HPLC, NMR and mass spectra were used to elucidate the purity and structure of compounds. Female A-J mice were treated with three limonoids and a mixture in order to evaluate their effect on phase II enzymes in four different tissues. Assays for glutathione S-transferase and NADPH: quinone reductase QR were used to evaluate induction of phase II enzymatic activity.

ResultsThe highest induction of GST against 1-chloro-2,4-dinitrobenzene CDNB was observed in stomach whole, 58% by nomilin, followed by 25% isoobacunoic acid and 19% deacetyl nomilin. Deacetyl nomilin in intestine small as well as liver significantly reduced GST activity against CDNB. Additionally isoobacunoic acid and the limonoid mixture in liver demonstrated a significant reduction of GST activity against CDNB. Nomilin significantly induced GST activity against 4-nitroquinoline 1-oxide 4NQO, intestine 280% and stomach 75% while deacetyl nomilin showed significant induction only in intestine 73%. Induction of GST activity was also observed in intestine 93% and stomach 45% treated with the limonoid mixture. Finally, a significant induction of NADPH: quinone reductase QR activity was observed by the limonoid mixture in stomach 200%. In addition, the deacetyl nomilin treatment group displayed an increase in QR activity in liver 183% and intestine 22%.

ConclusionThe results of the present study suggests that, dietary intake of citrus limonoids may provide a protective effect against the onset of various cancers by inducing the activity of certain phase II detoxifying enzymes in specific organs.

Hassan Ahmad and Bhimanagouda S Patil contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6882-10-51 contains supplementary material, which is available to authorized users.

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Author: Jose L Perez - Guddarangavvanahally K Jayaprakasha - Adriana Cadena - Elvia Martinez - Hassan Ahmad - Bhimanagouda S Pati


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