감송향이 TNF-α로 유도된 HaCaT 각질형성세포의 염증반응에 미치는 효과
Anti-inflammatory Effect of Nardostachys jatamansi on TNF-alpha-induced Inflammatory Response in HaCaT Cells
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초록
현재 다양한 피부문제 및 피부질환 개선을 위하여 스테로이 드제제 사용이 흔하게 이루어져 왔으나, 최근 천연물질로부터 얻어진 성분 등을 통하여 부작용 없이 문제를 보완하고 개선할 수 있는 천연물 개발에 대한 많은 연구가 진행되고 있다. 본 연구에서는 감송향 물 추출물을 사용하여 항염증 효과를 확인하 였으며, 다음과 같은 결론을 얻었다. 사람각질형성세포인 HaCaT 세포에 hTNF-α를 처리한 후 염증 매개인자 iNOS, COX2, PGE2의 발현양을 mRNA 및 단백질 수준에서 확인하였다. mRNA 수준에서 iNOS, COX2의 발현이 감송향 물 추출물의 농 도 의존적으로 유의하게 감소하였다. PGE2의 발현 또한 단백질 수준에서 감송향 물 추출물의 농도의존적으로 유의하게 감소하 였으며, hTNF-α 대조군에 비하여 감송향 50 μg/mL 농도에서 가 장 유의한 감소 (hTNF 대비 79.32% 억제)를 보였다. 전 염증성 사이토카인인 TNF-α와 IL-6의 생성을 mRNA 및 단백질 수준에 서 확인한 결과, mRNA 및 단백질 수준 모두에서 감송향 물 추 출물의 농도 의존적으로 TNF-α와 IL-6의 생성이 감소하였다. 단백질 수준에서 hTNF-α 대조군에 비하여 TNF-α의 생성이 감 송향 50 μg/mL 농도에서 가장 유의한 감소 (hTNF 대비 93.11% 억제)를 보였으며, IL-6의 생성 또한 감송향 50 μg/mL 농도에서 가장 유의한 감소 (hTNF 대비 66.87% 억제)를 보였다. HaCaT 세포에 hTNF-α를 처리한 후 ROS 생성을 확인하였 다. 그 결과 ROS의 발현이 감송향 물 추출물의 농도 의존적으 로 유의하게 감소하였으며, hTNF-α 대조군에 비하여 감송향 50 μg/mL 농도에서 가장 유의한 감소 (hTNF 대비 97.5% 억제)를 보였다. 이러한 감송향 물 추출물의 항염증 효과는 MAPKs 염 증신호전달기전 중 ERK와 JNK의 억제를 통하여 나타난 것을 확인하였다. 따라서 감송향 물 추출물은 피부미용관련 제품 개 발의 원료로서 화장품 소재로 활용이 가능할 것으로 사료된다.
Abstract
Nardostachys jatamansi (NJ) is a medical herb used to treat inflammatory diseases. This study sought to ascertain the beneficial effects of NJ on human tumor necrosis factor (hTNF)-α induced skin inflammation. HaCaT cells were pretreated with NJ for 1 h and stimulated with hTNF-α (10 ng/mL). After 24 h cells were harvested to measure inflammatory mediators, pro-inflammatory cytokine production, and reactive oxygen species (ROS). When HaCaT cells were treated only with hTNF-α, production of inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX) 2 and prostaglandin E2 (PGE2), and pro-inflammatory cytokines (such as TNF-α and interleukin (IL)-6) were increased dramatically. Also, hTNF-α treatment resulted in increased ROS production. However, the ROS and inflammatory mediaters production were inhibited by NJ extract treatment in hTNF-α treated HaCaT cells. To investigate the regulatory mechanisms of NJ extract, this study also assessed mitogen activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling pathways in HaCaT cells. NJ extract significantly inhibited hTNF-α induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal protein kinase (JNK), but not phosphorylation of p38 or inhibitor of kappa (Iκ)-Bα degradation. This could indicate that the NJ extract shows anti-inflammatory activity mainly through ERK and JNK. In conclusion, these results suggest that NJ exhibited anti-inflammatory activities against hTNFα-induced skin damage by inhibiting phosphorylation of ERK and JNK. Thus, we propose that NJ may be a promising skin protector, which could suggest the clinical basis for cosmetics development.
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