Epidemiological evidence suggests that flavonoids may play an important role in the decreased risk of chronic diseases associated with a diet rich in plant-derived foods. Flavonoids are also common constituents of plants used in traditional medicine to treat a wide range of diseases. The purpose of this article is to summarize the distribution and biological activities of one of the most common flavonoids: luteolin. This flavonoid and its glycosides are widely distributed in the plant kingdom; they are present in many plant families and have been identified in Bryophyta, Pteridophyta, Pinophyta and Magnoliophyta. Dietary sources of luteolin include, for instance, carrots, peppers, celery, olive oil, peppermint, thyme, rosemary and oregano. Preclinical studies have shown that this flavone possesses a variety of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial and anticancer activities. The ability of luteolin to inhibit angiogenesis, to induce apoptosis, to prevent carcinogenesis in animal models, to reduce tumor growth in vivo and to sensitize tumor cells to the cytotoxic effects of some anticancer drugs suggests that this flavonoid has cancer chemopreventive and chemotherapeutic potential. Modulation of ROS levels, inhibition of topoisomerases I and II, reduction of NF-kappaB and AP-1 activity, stabilization of p53, and inhibition of PI3K, STAT3, IGF1R and HER2 are possible mechanisms involved in the biological activities of luteolin.

Distribution and biological activities of the flavonoid luteolin.

Flavones: An important scaffold for medicinal chemistry

Luteolin as an anti-inflammatory and neuroprotective agent: A brief review

Focal cerebral ischemia is associated with expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), enzymes whose reaction products contribute to the evolution of ischemic brain injury. We tested the hypothesis that, after cerebral ischemia, nitric oxide (NO) produced by iNOS enhances COX-2 activity, thereby increas- ing the toxic potential of this enzyme. Cerebral ischemia was produced by middle cerebral artery occlusion in rats or mice. Twenty-four hours after ischemia in rats, iNOS-immunore- active neutrophils were observed in close proximity (<20 mm) to COX-2-positive cells at the periphery of the infarct. In the olfactory bulb, only COX-2 positive cells were observed. Cerebral ischemia increased the concentration of the COX-2 reaction product prostaglandin E2 (PGE2) in the ischemic area and in the ipsilateral olfactory bulb. The iNOS inhibitor aminoguanidine reduced PGE2 concentration in the infarct, where both iNOS and COX-2 were expressed, but not in the olfactory bulb, where only COX-2 was expressed. Postischemic PGE2 accumulation was reduced significantly in iNOS null mice compared with wild-type controls (C57BLy6 or SV129). The data provide evidence that NO produced by iNOS inf lu- ences COX-2 activity after focal cerebral ischemia. Pro- inf lammatory prostanoids and reactive oxygen species pro- duced by COX-2 may be a previously unrecognized factor by which NO contributes to ischemic brain injury. The patho- genic effect of the interaction between NO, or a derived specie, and COX-2 is likely to play a role also in other brain diseases associated with inf lammation.

Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia (middle cerebral artery occlusionyaminoguanidineyNS-398ygene expressionyinducible nitric oxide synthase null mice)

This review discusses the occurrence and distribution (within a plant) of methyl eugenol in different plant species (> 450) from 80 families spanning many plant orders, as well as various roles this chemical plays in nature, especially in the interactions between tephritid fruit flies and plants.

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Methyl Eugenol: Its Occurrence, Distribution, and Role in Nature, Especially in Relation to Insect Behavior and Pollination

Neuroprotective effects of flavones on hydrogen peroxide-induced apoptosis in SH-SY5Y neuroblostoma cells

Neuroprotective effects of naturally occurring biflavonoids.

The present study tested the cytoprotective effect of methyleugenol in an in vivo ischemia model (i.e. middle cerebral artery occlusion (MCAO) for 1.5 h and subsequent reperfusion for 24 h) and further investigated its mechanism of action in in vitro cerebral ischemic models. When applied shortly after reperfusion, methyleugenol largely reduced cerebral ischemic injury. Methyleugenol decreased the caspase-3 activation and death of cultured cerebral cortical neurons caused by oxygen-glucose deprivation (OGD) for 1 h and subsequent re-oxygenation for 24 h. Methyleugenol markedly reduced superoxide generation in the ischemic brain and decreased the intracellular oxidative stress caused by OGD/re-oxygenation. It was found that methyleugenol elevated the activities of superoxide dismutase and catalase. Further, methyleugenol inhibited the production of nitric oxide and decreased the protein expression of inducible nitric oxide synthase. Methyleugenol down-regulated the production of pro-inflammatory cytokines in the ischemic brain as well as in immunostimulated mixed glial cells. The results indicate that methyleugenol could be useful for the treatment of ischemia/inflammation-related diseases.

Methyleugenol reduces cerebral ischemic injury by suppression of oxidative injury and inflammation.

MKP-1 contributes to oxidative stress-induced apoptosis via inactivation of ERK1/2 in SH-SY5Y cells

－ Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke. Keywords: Polyethylene glycol-conjugated hemoglobin, Hypoxia, Focal cerebral ischemia INTRODUCTION The brain is more vulnerable to ischemic insults than any other organs. The level of oxygen in brain depends on cerebral blood flow and arterial oxygen content. Normal cerebral blood flow is approximately 50 ml/100 g/min. When cerebral blood flow drops below a critical level of 10 ml/100 g/min, irreversible brain damage occurs, with its ensuing metabolic derangement (Pulsinelli, 1992). Even when cerebral blood flow falls to 25 ml/100 g/min, neuronal cells become electrically silent, although they remain po-tentially viable (Hossman, 1994). Therefore, augmentation of oxygen delivery into hypoxic/ischemic lesions would be beneficial to prevent further neurological deterioration in stroke. Development of artificial blood substitutes has been mo-tivated by insufficient blood supply, dangers of blood in-compatibility reactions, and/or infectious diseases in ho-mologous blood transfusion. Furthermore, hemoglobin- based oxygen carriers can be sterilized and stored for pro-longed periods of time. For decades, free hemoglobin de-rived from hemolyzed blood or hemoglobin-based oxygen carriers have been designed as temporary substitutes to red blood cells (Winslow, 2008). Artificial oxygen carriers are grouped into hamoglobin-based oxygen carriers and perfluorocarbon emulsions (Spahn and Kocian, 2005). Several of hemoglobin-based oxygen carriers, including cross-linked hemoglobin, polyethylene glycol (PEG)-con-jugated hemoglobin (PEG-Hb), and recombinant hemoglo-bin, have been demonstrated to maintain circulating vol-ume (Hu

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Yoo Keum Choi

Papers

Neuroprotective effects of flavones on hydrogen peroxide-induced apoptosis in SH-SY5Y neuroblostoma cells

Neuroprotective effects of naturally occurring biflavonoids.

Methyleugenol reduces cerebral ischemic injury by suppression of oxidative injury and inflammation.

MKP-1 contributes to oxidative stress-induced apoptosis via inactivation of ERK1/2 in SH-SY5Y cells

Attenuated Cerebral Ischemic Injury by Polyethylene Glycol-Conjugated Hemoglobin