title: Antioxidant and Nrf2 inducing activities of luteolin, a flavonoid constituent in Ixeris sonchifolia Hance, provide neuroprotective effects against ischemia-induced cellular injury.
abstract: Ixeris sonchifolia Hance is an herb distributed in northeastern part of China and has been used by natives to invigorate circulation. In the present study, bioactivity-guided fractionation of I. sonchifolia Hance extract was performed with the aim to isolate and identify the compounds underlying the potential protective effects against ischemia brain injury. Among the four fractions isolated from the herb extract, the ethyl acetate fraction was found to scavenge DPPH radicals, induce ARE-dependent transcriptional activity and upregulate Nrf2 protein levels. The isolation work focused on this fraction revealed the presence of two categories of compounds: flavonoids and sesquiterpene lactones. Among the five isolated flavonoids, luteolin was evaluated to possess direct and indirect antioxidant activities by scavenging free radicals and inducing the upregulation of ARE-dependent phase II enzymes. Concomitant with the findings from the cell-based assays, in the middle cerebral artery occlusion-induced ischemia rat model, administration of luteolin at 4 mg/kg displayed neuroprotective effects by reducing infarct area and inhibiting neuronal cell death. In summary, the obtained results suggest that flavonoids in I. sonchifolia Hance, in particular luteolin, contribute at least partly to the neuroprotective effects against ischemia-induced cellular injury and can be potentially developed for treatment of ischemia-reperfusion induced diseases.
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore 117543, Republic of Singapore.
authors.forename: Yao-Chun
authors.initials: YC
authors.lastname: Zhang
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Gan
authors.forename: Sandeep Balu
authors.initials: SB
authors.lastname: Shelar
authors.forename: Ka-Yun
authors.initials: KY
authors.lastname: Ng
authors.forename: Eng-Hui
authors.initials: EH
authors.lastname: Chew
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D019659:Asteraceae / Q000737:chemistry; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020834:Ethnopharmacology; D006801:Humans; D047311:Luteolin / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D010296:Parietal Lobe / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D020218:Response Elements / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D047311:Luteolin
keywords: ARE; Antioxidant activity; HO-1; Ixeris sonchifolia Hance; Keap1; Kelch-like erythroid cellderived protein with CNC homology (ECH)-associated protein 1; Luteolin; MCAO; Middle cerebral artery occlusion; Neuroprotection; Nrf2; Nrf2 induction; antioxidant response element; heme oxygenase-1; middle cerebral artery occlusion; nuclear factor erythroid 2-related factor 2