Antioxidant and Nrf2 inducing activities of luteolin, a flavonoid constituent in Ixeris sonchifolia Hance, provide neuroprotective effects against ischemia-induced cellular injury

• Published in: Food and chemical toxicology Vol. 59; pp. 272 - 280
• Main Authors: Zhang, Yao-Chun, Gan, Fei-Fei, Shelar, Sandeep Balu, Ng, Ka-Yun, Chew, Eng-Hui
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2013; Elsevier
• Subjects: animal models; Animals; Antioxidant activity; antioxidants; Antioxidants - isolation & purification; Antioxidants - pharmacology; Antioxidants - therapeutic use; Asteraceae - chemistry; Biological and medical sciences; brain; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cell Hypoxia - drug effects; Cell Line; Cell Survival - drug effects; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; enzymes; Ethnopharmacology; ethyl acetate; fractionation; free radicals; Humans; infarction; ischemia; Ixeris sonchifolia Hance; Luteolin; Luteolin - isolation & purification; Luteolin - pharmacology; Luteolin - therapeutic use; Male; Medical sciences; Middle cerebral artery occlusion; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; neurons; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotection; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; neuroprotective effect; NF-E2-Related Factor 2 - biosynthesis; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nrf2 induction; Parietal Lobe - blood supply; Parietal Lobe - drug effects; Parietal Lobe - metabolism; Parietal Lobe - pathology; Rats; Rats, Sprague-Dawley; Reperfusion Injury - prevention & control; Response Elements - drug effects; sesquiterpenoid lactones; Toxicology; transcription (genetics); Transcription, Genetic - drug effects; China; MCAO; Neuroprotection; ARE; Nrf2; Antioxidant activity; Middle cerebral artery occlusion; Keap1; HO-1; Luteolin; Ixeris sonchifolia Hance; Nrf2 induction; Occlusion; Toxicity; Middle cerebral artery; Cardiovascular disease; Activity; Neuroprotective agent; Antioxidant; Flavonoid; Micronutrient; Polyphenol; Ischemia; Plant origin; Phenols; Proanthocyanidin; Kelch-like erythroid cellderived protein with CNC homology (ECH)-associated protein 1; heme oxygenase-1; nuclear factor erythroid 2-related factor 2; antioxidant response element
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.05.058

•The ethyl acetate fraction of I. sonchifolia Hance extract possessed radical scavenging and Nrf2 inducing activities.•Flavonoids and sesquiterpene lactones were identified in the ethyl acetate fraction of I. sonchifolia Hance extract.•Luteolin in I. sonchifolia Hance extract protected SH-SY5Y cells from H2O2-induced toxicity.•In the middle cerebral artery occlusion-induced ischemia rat model, luteolin treatment was found to reduce infarct area. 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 4mg/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.