• 생명과학회지
• /
• 제30권10호
• /
• pp.867-876
• /
• 2020

본 연구는 magnolol에 의한 UVB 유도 세포 손상의 복구를 조사하였다. 우리는 약물재배치를 위해 STAT3 기작을 분석하였고, magnolol HDF 세포에서 세포 생존력을 향상시키며, STAT3의 억제제인 것을 확인하였다. IL-6, UVB 및 IFNγ로 처리 된 HDF 세포는 Jak2 및 인산화 된 STAT3 (p-STAT3)의 높은 발현을 나타냈다. Magnolol 의 처리는 UVB 유도 세포에서 Jak2 및 p-STAT3의 발현을 감소시킬 수 있었다. 또한, UVB- 손상된 세포 성장은 용량 의존적 방식으로 재 활성화 및 magnolol 과의 상관 관계가 상당히 증가되었다. UVB 처리 된 HDF 세포에 대한 AG490 (Jak2 억제제) 처리와 비교하여, 세포 증식이 유의하게 증가 하였다. 우리는 AG490 및 magnolol 이 TNF-α 농도를 감소시키는 것을 확인했다. Western blot (단백질 수준)은 오직 magnolol 처리 된 세포에서만 Jak2 및 p-STAT3 발현의 감소를 나타냈고, Jak2, p-STAT3 및 SOCS3의 발현은 또한 magnolol 처리한 세포에서만 증가하였다. 세포를 magnolol 및 ML385 (NRF2 억제제)로 동시 처리시 세포 증식 및 NRF2 발현을 감소시켰다. MMP9의 양은 magnolol 및 ML385 로의 처리에 의해 증가되었다. 종합적으로, 이들 결과는 NRF2, SOCS3, Jak2 및 STAT3의 발현을 조절함으로써 UVB 손상 후 세포를 회복시키는데 있어 magnolol의 가능성을 입증한다.

• 생약학회지
• /
• 제47권1호
• /
• pp.55-61
• /
• 2016

Antioxidant effects and nuclear factor E2-related factor-2 (Nrf-2) signal pathway of methanol extract and 4 fractions [n-hexane, methylene chloride, ethyl acetate (EtOAc), and n-butanol fractions] from Petasites japonicus were investigated. The EtOAc fraction showed highest polyphenol and flavonoid contents among other fractions. In addition, EtOAc fraction showed stronger scavenging activity against superoxide anion radical than other fractions. Furthermore, we investigated antioxidants effects of the EtOAc fraction under cellular system using $LLC-PK_1$ cells. The EtOAc fraction dose-dependently increased the antioxidant protein expressions of heme oxygenase 1 (HO-1) and thioredoxin reductase 1 (TrxR1) known to be involved in oxidative stress, through activation of Nrf-2. The treatment of EtOAc fraction ($100{\mu}g/mL$) led to the elevation of the high expression of Nrf-2-dependent factor such as HO-1 and TrxR1. These results indicated that the EtOAc fraction of P. japonicus showed high antioxidant activity by regulation of Nrf-2 signaling pathway.

• Bulletin of the Korean Chemical Society
• /
• 제34권8호
• /
• pp.2317-2320
• /
• 2013

Thiourea and vinyl sulfoxide derivatives were designed based on the structures of sulforaphane and gallic acid, prepared and tested for HO-1 inducing activity as a measure of Nrf2 activation, and inhibitory effect on NO production as a measure of anti-inflammatory activity. Both series of compounds showed moderate activity on HO-1 induction, and no inhibitory effect on NO production. Interestingly the thiourea compound 6d showed better HO-1 induction (71% SFN) than the corresponding isothiocyanate compound 6a (55% SFN). Overall, it seemed that more efficient electrophile is needed to get more effective Nrf2 activator.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권23호
• /
• pp.10439-10444
• /
• 2015

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

• 대한본초학회지
• /
• 제30권4호
• /
• pp.57-64
• /
• 2015

Objectives : Oxidative stress is one of the most causes of hepatocyte injury. Gleditsia spina, the thorns ofGleditsia sinensisLam., has been known for its anti-cancer and anti-inflammatory effects in Korean medicine. The present study investigated hepatoprotective effect of Gleditsia spina water extract (GSE) against oxidative stress induced by arachidonic acid (AA) + iron in HepG2 cells.Methods : To investigate cytoprotective effect of GSE, cells were pretreated with GSE and then subsequently exposed to 10 μM AA for 12 h, followed by 5 μM iron. Cell viability was monitored by MTT assay, and expression of apoptosis-related proteins was examined by immunoblot analysis. To identify responsible molecular mechanisms, reactive oxygen species (ROS) production, GSH contents, and mitochondrial membrane potential were measured. In addition, effect of GSE on nuclear factor erythroid 2-related factor 2 (Nrf2) activation was determined by immunoblot and antioxidant response element (ARE)-driven reporter gene assays.Results : GSE pretreatment prevented AA + iron-mediated cytotoxicity in concentration dependent manner. In addition, ROS production, glutathione depletion, and mitochondrial impairment by AA + iron were significantly inhibited by GSE. Furthermore, GSE promoted translocation of Nrf2 to nucleus, which acts as essential transcription factor for induction of antioxidant genes. Increased nuclear Nrf2 that caused by GSE treatment promoted transcriptional activity of ARE. Finally, GSE up-regulated sestrin-2 which was widely recognized as target gene of Nrf2.Conclusions : This study demonstrates that GSE protects hepatocytes from oxidative stress via activation of Nrf2 signaling pathway.

• 동의생리병리학회지
• /
• 제31권1호
• /
• pp.75-81
• /
• 2017

Dangguisoo-san (DGSS), a traditional Korean herbal formula, has been prescribed to patients who suffer from various symptoms related with blood stagnation. Since inflammation can cause blood stagnation, we hypothesized that DGSS suppresses inflammation, relieving the symptoms associated with blood stagnation. In this study, given that DGSS is prepared in a mix of alcohol and water, we prepared the methanol (mDGSS) and water extract (wDGSS) of DGSS and compared their activities in suppressing inflammatory reaction. Western blot analyses show that mDGSS was more effective than wDGSS in activating Nrf2, a key factor that suppresses inflammation. Semi-quantitative RT-PCR shows that mDGSS activating Nrf2 resulted in the induction of Nrf2-dependent genes expression. However, mDGSS was not effective in suppressing the nuclear translocation of $NF-{\kappa}B$, a key factor that promotes inflammation, and the expression of $NF-{\kappa}B$-dependent genes such as TNF-a and IL-1b. When comparing with wDGSS, mDGSS was less effective in suppressing luciferase activity driven by $NF-{\kappa}B$. Therefore, our results show that mDGSS has the anti-inflammatory function by mainly activating Nrf2, while wDGSS does by both activating Nrf2 and suppressing $NF-{\kappa}B$. Our results suggest that preparing DGSS in a mix of water and methanol is a better way to achieve a strong anti-inflammatory efficacy of DGSS.

• Journal of Ginseng Research
• /
• 제47권4호
• /
• pp.561-571
• /
• 2023

Background: Escalating evidence shows that ginseng possesses an antiaging potential with cognitive enhancing activity. As mountain cultivated ginseng (MCG) is cultivated without agricultural chemicals, MCG has emerged as a popular herb medicine. However, little is known about the MCG-mediated pharmacological mechanism on brain aging. Methods: As we demonstrated that glutathione peroxidase (GPx) is important for enhancing memory function in the animal model of aging, we investigated the role of MCG as a GPx inducer using GPx-1 (a major type of GPx) knockout (KO) mice. We assessed whether MCG modulates redox and cholinergic parameters, and memory function in aged GPx-1 knockout KOmice. Results: Redox burden of aged GPx-1 KO mice was more evident than that of aged wild-type (WT) mice. Alteration of Nrf2 DNA binding activity appeared to be more evident than that of NFκB DNA binding activity in aged GPx-1 KO mice. Alteration in choline acetyltransferase (ChAT) activity was more evident than that in acetylcholine esterase activity. MCG significantly attenuated reductions in Nrf2 system and ChAT level. MCG significantly enhanced the co-localization of Nrf2-immunoreactivity and ChAT-immunoreactivity in the same cell population. Nrf2 inhibitor brusatol significantly counteracted MCG-mediated up-regulation in ChAT level and ChAT inhibition (by k252a) significantly reduced ERK phosphorylation by MCG, suggesting that MCG might require signal cascade of Nrf2/ChAT/ERK to enhance cognition. Conclusion: GPx-1 depletion might be a prerequisite for cognitive impairment in aged animals. MCG-mediated cognition enhancement might be associated with the activations of Nrf2, ChAT, and ERK signaling cascade.

• Bulletin of the Korean Chemical Society
• /
• 제35권12호
• /
• pp.3623-3626
• /
• 2014

Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates the expression of over 200 genes of antioxidant and phase II drug-metabolizing enzymes, and is highly expressed in non-small cell lung cancer (NSCLC). Nine derivatives of 4-(2-cyclohexylethoxy)aniline were designed. Our previous study demonstrated that IM3829 increases radiosensitivity of several lung cancer cells in vitro and in vivo. Here, biological effects of IM3829 derivatives (2a-2i) were evaluated. Compound 2g derivative effectively inhibits mRNA and protein expression of Nrf2 and HO-1. In addition, we observed over two fold enhancement in IR-induced cell death, from $2.90{\pm}0.22$ to $6.02{\pm}0.87$, in H1299 cancer cell-line. Among the nine derivatives, compound 2g derivative exhibited the highest enhancement of radiosensitizing effect via inhibition of Nrf2 activity.

• 한국환경성돌연변이발암원학회:학술대회논문집
• /
• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
• /
• pp.180-180
• /
• 2003

• 한국식생활문화학회지
• /
• 제38권5호
• /
• pp.365-372
• /
• 2023

Ipomoea aquatic is a leafy vegetable of the Convolvulaceae family, and is a tropical plant widely inhabiting southern China and Southeast Asia, and is widely known as Morning Glory in the West. In this study, the anti-inflammatory effects of ethyl acetate extract from Ipomoea aquatic extracts (IAE) were tested against lipopolysaccharide (LPS)-induced activation microglia BV2 cells. The production of nitric oxide (NO) and cell viability were measured using the Griess reagent and MTT assay, respectively. Inflammatory cytokine [interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interleukin-1β (IL-1β)] were detected qPCR in LPS induced BV-2 cells. Subsequently, nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs), and nuclear factor erythroid-2-related factor 2 (Nrf2) were analyzed through western blot analyses and immunofluorescence. Ipomoea aquatic down-regulated of inflammatory markers and up-regulated anti-inflammatory and anti-oxidants in BV2 cells.