Page 12 - H. Cell signaling

[H. Cell signaling-6]

9-Hydroxy-Isoegomaketone Inhibits Anti-Inflammatory

Activity in LPS-Stimulated RAW 264.7 Macrophages through

the Activation of Nrf2 and Induction of HO-1

Hyun Mi Kim¹˙², Bomi Nam¹, Sunil Babu Paudel³, Joo- Won Nam³, Ah- Reum Han¹, Hye Gwang Jeong²,

Chang Hyun Jin¹˙*

¹Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si 56212, Republic of

Korea, ²College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea, ³College of
Pharmacy, Yeungnam University, Gyeongsan-si 38541, Republic of Korea

9-hydroxy-isoegomaketone (9-HIK), a new compound, was isolated from the radiation mutant cultivar Perilla

frutescens var. crispa. In this study, we aimed to confirm anti-inflammatory effects of 9-HIK. The results showed that
9-HIK reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated

RAW 264.7 cells. 9-HIK also inhibited the production of inflammatory mediators, including interleukin 6 (IL-6),
interleukin 1β (IL-1β), and interferon β (IFN-β) in LPS-stimulated RAW 264.7 cells in a dose-dependent manner.

Furthermore, 9-HIK induced the expression of heme oxygenase-1 (HO-1) that showed anti-oxidant and anti-
inflammatory activities through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). 9-HIK led to an

increase in HO-1 protein levels, showing a maximal level at 4 h after treatment. Treatment with N-acetyl-L-cysteine
(NAC), a ROS scavenger, suppressed the 9-HIK induced HO-1 mRNA expression level and it reversed the 9-HIK-

induced suppression of NO production. Taken together, 9-HIK inhibits NO production in LPS-stimulated RAW 264.7
cells through activation of Nrf2 and induction of HO-1.