http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
이응룡,강근호,강용진,김우열,최혜연,김봉우,정효순,조쌍구 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10
Many studies revealed the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. The plausible mechanistic interpretation of the various effects of flavonoids was concentrated on the anti-oxidant or free radical-scavenging properties of these phytochernicals, both in model systems and under in vivo conditions. While there has been a major focus on the anti-oxidant properties. there is an emerging view that flavonoids and their in vivo metabolites. do not act as conventional hydrogen-donating anti-oxidants. but they may exert regulatory functions in cells through actions at protein kinase or lipid kinase signaling pathways. Flavonoids and more recently their metabolites. have been reported to act at phosphoinositide 3-kinase(PI 3-kinase). Akt/protein kinase B(Akt/PKB), protein kinase C (PKC), mitogen activated protein kinase(MAP kinase), and various tyrosine kinases signaling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as anti-oxidants or modulators of cellular signaling pathways, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anti-cancer agents, cardio-protectants, and inhibitors of neurodegeneration.
Lee, Eung-Ryoung,Kang, Yong-Jin,Choi, Hye-Yeon,Kang, Geun-Ho,Kim, Jung-Hyun,Kim, Bong-Woo,Han, Ye Sun,Nah, Seung-Yeol,Paik, Hyun-Dong,Park, Yong-Sun,Cho, Ssang-Goo Pharmaceutical Society of Japan 2007 Biological & pharmaceutical bulletin Vol.30 No.12
<P>Although flavonoids, which are both qualitatively and quantitatively one of the largest groups of natural products, exhibit a variety of beneficial health effects, the exact molecular mechanism of the cellular activities is still not fully explained and there currently exists a lack of evidence for any relationship between the structure–activity relationship and apoptosis-inducing activity. In order to determine the importance of the OH group or substitution of the 5 or carbon-7 in the diphenylpropane skeleton of flavonoids, we originally synthesized several modified naringenin derivatives, including 7-<I>O</I>-benzyl naringenin (KUF-1) and 7-<I>O</I>-(MeO-<SMALL>L</SMALL>-Leu-<SMALL>D</SMALL>-Pro-carbonylmethyl) naringenin (KUF-7). Treatment with KUF-1 or KUF-7 resulted in significant apoptosis-inducing effects concomitant with chromatin condensation, caspase activation, and intracellular ROS production. Our data indicate that originally synthesized naringenin derivatives, KUF-1 and KUF-7 differentially regulate the apoptosis of A549 cells <I>via</I> intracellular ROS production coupled with the concomitant activation of the caspase cascade signaling pathway, thereby implying that hydroxylation or substitution at Carbon-7 is critical for the apoptosis-inducing activity of flavonoids.</P>
The Anti-apoptotic and Anti-oxidant Effect of Eriodictyol on UV-Induced Apoptosis in Keratinocytes
Lee, Eung-Ryoung,Kim, Jung-Hyun,Kang, Yong-Jin,Cho, Ssang-Goo Pharmaceutical Society of Japan 2007 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.30 No.1
<P>Recently, considerable scientific and therapeutic interest has focused on the structure and functions of the flavonoids. In a previous study, we suggested that hydroxyl (OH) substitutions on specific carbons in the skeleton of the flavonoids might significantly affect their apoptosis-modulating properties. Here, to investigate the effect of various OH substitutions on their diphenylpropane (C6C3C6) skeleton carbons, we selected 10 different flavonoids and assessed their role on UV-induced apoptosis of human keratinocytes, the principal cell type of epidermis. The results showed that 5,7,3′,4′-tetrahydroxylflavanone (eriodictyol) and 3,4′-dihydroxy flavone (3,4′-DHF) had a positive effect on cell proliferation of human HaCaT keratinocytes. Treatment with eriodictyol in particular resulted in significant suppression of cell death induced by ultraviolet (UV) light, a major skin-damaging agent. We found that eriodictyol treatment apparently reduced the percentage of apoptotic cells and the cleavage of poly(ADP-ribose) polymerase, concomitant with the repression of caspase-3 activation and reactive oxygen species (ROS) generation. The anti-apoptotic and anti-oxidant effects of eriodictyol were also confirmed in UV-induced cell death of normal human epidermal keratinocyte (NHEK) cells. Taken together, these findings suggest that eriodictyol can be used to protect keratinocytes from UV-induced damage, implying the presence of a complex structure–activity relationship (SAR) in the differential apoptosis-modulating activities of various flavonoids.</P>
Regulation of apoptosis by modified naringenin derivatives in human colorectal carcinoma RKO cells
Lee, Eung-Ryoung,Kang, Yong-Jin,Kim, Hyun-Jeong,Choi, Hye-Yeon,Kang, Geun-Ho,Kim, Jung-Hyun,Kim, Bong-Woo,Jeong, Hyo-Soon,Park, Yong-Sun,Cho, Ssang-Goo Wiley Subscription Services, Inc., A Wiley Company 2008 Journal of cellular biochemistry Vol.104 No.1
<P>Flavonoids are micronutrients that are widely detected in foods of plant origin and have been ascribed pharmacological properties. Several biological functions of flavonoids have been thus far identified, whereas there currently exists a lack of evidence to support the relationship between the structure-activity relationship and apoptosis-inducing activity. In an attempt to determine the importance of the OH group or substitution of the 5- or 7-carbon in the diphenylpropane skeleton of flavonoids, we selected 14 different flavonoids with different structures, particularly with regard to the 5- or 7-carbon, and found that naringenin treatment caused a slight decrease in the cell viability of the human colorectal carcinoma RKO cells. Next, in order to characterize the effects of specific substitutions of the 7-carbon of naringenin on apoptosis-regulatory activities, and in an attempt to develop anti-proliferative flavonoid derivatives that would be more effective against colon cancer, we originally synthesized several modified naringenin derivatives (MNDs) including 7-O-benzyl naringenin (KUF-1) and 7-O-(m-metoxybenzyl) naringenin (KUF-2). Treatment with KUF-1 or KUF-2 resulted in significant apoptosis-inducing effects concomitant with losses in mitochondrial membrane potential, caspase activation, intracellular ROS production, and sustained ERK activation. Our data show that KUF-1 or KUF-2 regulate the apoptosis of RKO cells via intracellular ROS production coupled with the concomitant activation of the ERK signaling pathway, thereby implying that hydroxylation or substitution at C7 is critical for the apoptosis-inducing activity of flavonoids. J. Cell. Biochem. 104: 259–273, 2008. © 2007 Wiley-Liss, Inc.</P>
Lee, Eung-Ryoung,Kim, Jung-Hyun,Choi, Hye Yeon,Jeon, Kilsoo,Cho, Ssang-Goo S. Karger AG 2011 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY Vol.27 No.5
<P>Although flavonoids exhibit a variety of beneficial biological activities, the exact molecular mechanism of the cellular effects is still not fully explained. In this study, we investigated the molecular mechanism of cytoprotective effect of eriodictyol in UV-irradiated keratinocytes. We found that treatment with eriodictyol effectively suppressed the UV-induced cell death of the keratinocytes, concomitant with the inhibition of pro-caspase-3 or pro-caspase-9 cleavage and the suppression of cytochrome C release. The phosphorylation of p38 MAPK was suppressed during UV-induced apoptosis of the keratinocytes and eriodictyol could reverse the down-regulation of p38 MAPK upon UV irradiation. Inhibition of p38 MAPK activity by SB202190, or over-expression of dominant-negative mutant form of p38 MAPK resulted in suppression of cytoprotective effect of the flavonoid. PP2A appeared to participate in the regulation of both p38 MAPK and Akt activities by directly associating with the kinases. UV treatment stimulated not only the phosphatase activity, but also its association with p38 MAPK or Akt. Interestingly, eriodictyol reversed the increase in PP2A activity and the association between the proteins. Taken together, these findings suggest that eriodictyol may lead to protection of keratinocytes from UV-induced cytotoxicity by modulating both the p38 MAPK and Akt signaling pathways in a phosphatase-dependent manner.</P><P>Copyright © 2011 S. Karger AG, Basel</P>
Lee, Eung-Ryoung,Kang, Yong-Jin,Choi, Hye-Yeon,Kang, Geun-Ho,Kim, Jeong-Hyun,Kim, Bong-Woo,Han, Ye Sun,Nah, Seung-Yeol,Paik, Hyun-Dong,Park, Yong-Sun,Cho, Ssang-Goo 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10
Although flavonoids, which are both qualitatively and quantitatively one of the largest groups of natural products, exhibit a variety of beneficial health effects, the exact molecular mechanism of the cellular activities is still not fully explained and there currently exists a lack of evidence for any relationship between the structure-activity relationship and apoptosis-inducing activity. In order to determine the importance of the OH group or substitution of the 5 or carbon-7 in the diphenylpropane skeleton of flavonoids, we originally synthesized several modified naringenin derivatives, including 7-O-benzyl naringenin (KUF-1) and 7-0-(MeO-L-Leu-D-Pro-carbonylmethyl) naringenin (KUF-7). Treatment with KUF-1 or KUF-7 resulted in significant apoptosisinducing effects concomitant with chromatin condensation, caspase activation, and intracellular ROS production. Our data indicate that originally synthesized naringenin derivatives, KUF-l and KUF-7 differentially regulate the apoptosis of A549 cells via intracellular ROS production coupled with the concomitant activation of the caspase cascade signaling pathway, thereby implying that hydroxylation or substitution at Carbon-7 is critical for the apoptosis-inducing activity of flavonoids.