Induction of detoxifying enzyme by sesquiterpenes present in Inula helenium.
Our previous study showed that the methanolic extract of Inula helenium (elecampane) had the potential to induce detoxifying enzymes such as quinine reductase (QR) and glutathione S-transferase. In this study we further fractionated the methanolic extract into hexane-, dichloromethane-, butanol-, and water-soluble fractions according to polarity. The hexane fraction showed the highest QR-inducing activity and also induced glutathione S-transferase in a dose-dependent manner. Its potential to induce the reporter activity suggested an antioxidant response element-mediated mechanism of action in the induction of phase II detoxifying enzymes. Intraperitoneal injection of the hexane fraction of I. helenium into ICR mice caused a significant increase of QR activity in liver, kidney, small intestine, and stomach. Sesquiterpenes, isolated from the hexane fraction, appeared to be major components responsible for QR induction. Among the seven compounds tested in this study, alantolactone, isoalantolactone, and 5alpha-epoxyalantolactone significantly induced QR activity in both Hepa1c1c7 and BPRc1 cells. In conclusion, sesquiterpenes, including alantolactone, isoalantolactone and 5-epoxyalantolactone, present in I. helenium merit further evaluation as chemopreventive agents.
Lim
Soon Sung
SS
Regional Innovation Center and Department of Food Science and Nutrition, Hallym University, Chuncheon, Republic of Korea.
Im
Sun Seong
SS
Kim
Ju Ryoung
JR
Lim
Hyun Ae
HA
Jang
Chan Ho
CH
Kim
Young Kyoon
YK
Konishi
T
T
Kim
Eun Ji
EJ
Park
Jung Han Yoon
JH
Kim
Jong-Sang
JS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression; D005982:Glutathione Transferase / Q000378:metabolism*; D006586:Hexanes; D006801:Humans; D007274:Injections, Intraperitoneal; D038143:Inula / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D050217:Metabolic Detoxication, Phase II; D051379:Mice; D008813:Mice, Inbred ICR; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D020218:Response Elements / Q000235:genetics; D012717:Sesquiterpenes / Q000494:pharmacology*; D014162:Transfection
D000975:Antioxidants; D006586:Hexanes; D010936:Plant Extracts; D012717:Sesquiterpenes; D008156:Luciferases; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase