Amentoflavone-induced oxidative stress activates NF-E2-related factor 2 via the p38 MAP kinase-AKT pathway in human keratinocytes

Wahyudi, Lilik Duwi,Jeong, Jiwon,Yang, Heejung,Kim, Jung-Hwan Elsevier 2018 The international journal of biochemistry & cell b Vol.99 No.-

<P><B>Abstract</B></P> <P>Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that responds to oxidative stress and xenobiotics. Multiple lines of evidence suggest that Nrf2 activation protects against aging, inflammation, and many diseases, including cancer. Nrf2 activators derived from natural sources have been widely studied. In this study, we investigated the effect of amentoflavone (AFN), a biflavonoid found in many plants, on Nrf2 signaling in human keratinocytes (HaCaT cells). AFN significantly increased ARE luciferase activity by Nrf2 accumulation in the nucleus. Subsequently, the levels of a Nrf2 target protein, NQO-1, were significantly increased by AFN in a dose- and time-dependent manner. To verify the mechanism of AFN-induced activation of Nrf2 signaling, we measured generation of reactive oxygen species (ROS). Interestingly AFN triggered mild ROS production. Additionally, AFN-induced Nrf2 activation was inhibited by N-acetyl cysteine. Therefore, we studied the effect of ROS-related signaling on Nrf2 by measuring the activation of AKT and members of the mitogen-activated protein kinase family, such as extracellular signal-regulated kinase (ERK1/2) and p38. The results showed that the pharmacological inhibitor of PI3K/AKT (LY294002) or p38 (SB 203580), but not ERK1/2 (U0126), abrogated AFN-induced Nrf2 activation. Subsequently, we found that silencing or inhibition of p38 resulted in decrease of AKT phosphorylation as well as inhibition of Nrf2 accumulation. Furthermore, we found that AFN stabilized Nrf2 by inhibiting its ubiquitination. Taken together, our results suggest that AFN contributes to Nrf2 activation through ROS-mediated activation of the p38-AKT pathway in HaCaT cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Amentoflavone induces Nrf2 activation in HaCaT cells. </LI> <LI> The Nrf2 was activated by ROS-p38 MAP kinase-AKT pathways. </LI> <LI> Amentoflavone stabilizes the Nrf2 by inhibition of ubiquitination. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Nuclear Receptor PPARα Agonist Wy-14,643 Ameliorates Hepatic Cell Death in Hepatic IKKβ-Deficient Mice

Kim, Taehyeong,Wahyudi, Lilik Duwi,Gonzalez, Frank J.,Kim, Jung-Hwan The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.5

Inhibitor of nuclear factor kappa-B kinase beta ($IKK{\beta}$) plays a critical role in cell proliferation and inflammation in various cells by activating $NF-{\kappa}B$ signaling. However, the interrelationship between peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) and $IKK{\beta}$ in cell proliferation is not clear. In this study, we investigated the possible role of $PPAR{\alpha}$ in the hepatic cell death in the absence of $IKK{\beta}$ gene using liver-specific Ikkb-null ($Ikkb^{F/F-AlbCre}$) mice. To examine the function of $PPAR{\alpha}$ activation in hepatic cell death, wild-type ($Ikkb^{F/F}$) and $Ikkb^{F/F-AlbCre}$ mice were treated with $PPAR{\alpha}$ agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in the $Ikkb^{F/F-AlbCre}$ mice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in both Ikkb and $Ikkb^{F/F-AlbCre}$ mice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that $IKK{\beta}-derived$ hepatic apoptosis could be altered by $PPAR{\alpha}$ activation in conjunction with activation of $NF-{\kappa}B$ and STAT3 signaling.

Nuclear Factor Erythroid 2-Related Factor 2 Activating Triterpenoid Saponins from <i>Camellia japonica</i> Roots

Ko, Kiwon,Wahyudi, Lilik D.,Kwon, Yong-Soo,Kim, Jung-Hwan,Yang, Heejung American Chemical Society and American Society of 2018 Journal of natural products Vol.81 No.11

<P>Oxidative stress due to the presence of excess reactive oxygen species may cause cancers, aging, and many other conditions. Nuclear factor erythroid 2-related factor 2 (Nrf2) may control abnormal oxidative stress as a transcription factor by inducing antioxidant-related genes via antioxidant response elements (AREs) in the gene promoters. The 11 triterpenoid saponins (<B>1</B>-<B>11</B>) isolated from <I>Camellia japonica</I> roots were tested for ARE-luciferase activity and Nrf2 accumulation in human keratinocytes (HaCaT cells). The ARE-luciferase activity was significantly increased by compounds <B>1</B>-<B>11 (</B>25 μM) as a result of nuclear Nrf2 accumulation in the cells. Thus, these compounds may contribute to the induction of Nrf2 activity against oxidative damage in cells.</P> [FIG OMISSION]</BR>

Nuclear Receptor PPARα Agonist Wy-14,643 Ameliorates Hepatic Cell Death in Hepatic IKKβ-Deficient Mice

( Taehyeong Kim ),( Lilik Duwi Wahyudi ),( Frank J. Gonzalez ),( Jung-hwan Kim ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.5

Inhibitor of nuclear factor kappa-B kinase beta (IKKβ) plays a critical role in cell proliferation and inflammation in various cells by activating NF-κB signaling. However, the interrelationship between peroxisome proliferator-activated receptor α (PPARα) and IKKβ in cell proliferation is not clear. In this study, we investigated the possible role of PPARα in the hepatic cell death in the absence of IKKβ gene using liver-specific Ikkb-null (Ikkb^F/F-AlbCre) mice. To examine the function of PPARα activation in hepatic cell death, wild-type (Ikkb^F/F) and Ikkb^F/F-AlbCre mice were treated with PPARα agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in the Ikkb^F/F-AlbCre mice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in both Ikkb and Ikkb^F/F-AlbCre mice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that IKKβ-derived hepatic apoptosis could be altered by PPARα activation in conjunction with activation of NF-κB and STAT3 signaling.

Impulse Buying: The Influence of Impulse Buying Tendency, Urge to Buy and Gender on Impulse Buying of the Retail Customers

Agung UTAMA,Hunik Sri Runing SAWITRI,Budi HARYANTO,Lilik WAHYUDI 한국유통과학회 2021 유통과학연구 Vol.19 No.7

Purpose: The main purpose of this research is to examine the effect of impulse buying tendencies toward impulse buying, which is mediated by an urge to buy and moderated by the gender of the retail customers. Research design, data and methodology: This study uses a survey design. The sample consisted of several mall customers in Yogyakarta. Purposive sampling was used as the sampling technique. Data collection was carried out in two ways, distributing questionnaires online and directly giving questionnaires to mall customers. Results: The results of data analysis using structural equation modeling show that: 1). Impulse buying tendencies have a positive and significant effect on the urge to buy and impulse buying, 2). The effect of impulse buying tendencies on impulse buying were mediated by an urge to buy and moderated by gender. Conclusions: Theoretical implications of this research strengthen the concept/theory concerning the relationship of the impulse buying tendencies, urge to buy and impulse buying. The results of the study have some managerial implications. It can be used to reference retail store business in increasing the volume of retail customers purchases through impulse buying. The retail businesses can increase impulse buying which will trigger impulsive purchases and the company s sales and profitability

The Role of Website Quality, Positive Emotion and Personalized Advertising in Triggering Impulse Buying Behavior: A Study of Online Retailer in Indonesia

Agung UTAMA,Hunik Sri Runing SAWITRI,Budhi HARYANTO,Lilik WAHYUDI 한국유통과학회 2024 유통과학연구 Vol.22 No.2

Purpose: The primary objective of this study is to investigate the impact of website quality on impulse buying of the online retailer, which is mediated by positive emotion and moderated by personalized advertising. Research design, data and methodology: The present study used a survey methodology conducted on many user's smartphones. The sample in this study included 409 college students in Indonesia. Purposive sampling was used as the sampling technique. Data was collected by distributing questionnaires to many respondents through the Google Documents online survey. Results: The findings derived from the application of structural equation modelling for data analysis show that 1). Website quality affects impulse buying and positive emotion, and 2). The impact of website quality on impulse buying was mediated by positive emotion and moderated by personalized advertising. Conclusions: The findings presented in this study has significant theoretical implications that contribute to the existing concept on the relationship between website quality, positive emotion, personalized advertising and impulse buying. The findings of the research possess managerial implications. It can be used can as a reference in determining website quality and the appropriate personalized advertising that increases online impulse buying at online retailer In Indonesia.