Journal of the Society of Cosmetic Scientists of Korea (대한화장품학회지)

Society of Cosmetic Scientists of Korea (대한화장품학회)
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Skin Protective Effect of Methylated Marliolide through Induction of NRF2/ARE

메틸말리올라이드의 NRF2/ARE 유도를 통한 피부 세포 보호 효과

  • Received : 2018.07.30
  • Accepted : 2018.11.12
  • Published : 2018.12.30
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Abstract

In the present study, we have investigated whether methylated marliolide could induce NRF2 thereby exerting anti-oxidant effects. MTT assay showed that methylated marliolide did not exhibit cytotoxicity on HaCaT cells. Methylated marliolide induced a higher ARE-dependent luciferase activation in HaCaT ARE-GFP-luciferase cells, compared with resveratrol. In addition, exposure of methylated marliolide to HaCaT cells significantly induced NRF2 and transcriptionally activated HO-1 and NQO1, both of which are target genes of NRF2. Finally, methylated marliolide protected HaCaT cells against TPA-induced oxidative damages on nucleotides and lipids. Together, results shows that methylated marliolide could suppress oxidative damages through induction of NRF2 which implies that methylated marliolide might serve as a good candidate for novel cosmetic ingredient with anti-oxidant effects.

본 연구진은 메틸말리올라이드가 인간 피부 세포주인 HaCaT 세포에서 NRF2를 유도하고 이를 통하여 항산화 효과를 나타내는지 알아보았다. MTT assay를 통하여 메틸말리올라이드는 $10{\mu}M$ 농도에서 24 h 동안 HaCaT 세포에 처리하여도 HaCaT 세포 독성을 나타내지 않는 것을 확인하였다. 본 연구진이 구축한 HaCaT-ARE-GFP-luciferase 세포에 메틸말리올라이드를 처리하고 루시퍼라아제 활성을 측정한 결과 메틸말리올라이드는 양성 대조군인 레스베라트롤보다 ARE 결합에 따른 루시퍼라아제 활성을 더욱 강하게 증가시키는 것을 확인하였다. 또한 HaCaT 세포에 메틸말리올라이드 처리 시 NRF2에 의하여 유도되는 항산화 단백질인 HO-1과 NQO1 mRNA 및 단백질 발현이 통계적으로 유의하게 증가하였다. 마지막으로 메틸말리올라이드는 HaCaT 세포에서 TPA에 의해서 유도된 DNA 및 지질의 산화를 강력하게 억제하였다. 결론적으로 본 연구는 메틸말리올라이드가 NRF2 유도를 통하여 피부 산화적 스트레스를 억제하며 이는 메틸말리올라이드가 신규 항산화 화장품의 소재로 적합하다는 것을 시사한다.

Keywords

HJPHBN_2018_v44n4_375_f0001.png 이미지

Figure 1. A single step synthesis of methylated marliolide from marliolide whose synthetic scheme was previously reported[8].

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Figure 2. MTT assay shows that methylated marliolide does not affect the viability of HaCaT cells.

HJPHBN_2018_v44n4_375_f0003.png 이미지

Figure 3. Luciferase assay shows that methylated marliolide significantly activates ARE-luciferase activity in HaCaT-ARE-GFP-luciferase cells. Resveratrol was included as a positive control.

HJPHBN_2018_v44n4_375_f0004.png 이미지

Figure 4. Western blot shows that methylated marliolide induces HO-1, NQO1, and NRF2 in HaCaT cells. Resveratrol was included as a positive control.

HJPHBN_2018_v44n4_375_f0005.png 이미지

Figure 5. Methylated marliolide transcriptionally induces HO-1 and NQO1 in HaCaT cells.

HJPHBN_2018_v44n4_375_f0006.png 이미지

Figure 6. Immunofluorescence study shows that methylated marliolide suppress TPA-induced generation of 4-hydroxynonenal (4-HNE, Left Panel) and 8-oxodeoxyguanosine (8-OHdG, Right Panel) in HaCaT cells.

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