A fraction from Dojuksan 30% ethanol extract exerts its anti-inflammatory effects through Nrf2-dependent heme oxygenase-1 expression

Lee,Dong-Sung; Kim,Kyoung-Su; Ko,Wonmin; Bae,Gi-Sang; Park,Sung-Joo; Jang,Jun-Hyeog; Oh,Hyuncheol; Kim,Youn-Chul

doi:10.3892/ijmm.2015.2424

A fraction from Dojuksan 30% ethanol extract exerts its anti-inflammatory effects through Nrf2-dependent heme oxygenase-1 expression

Authors:
- Dong-Sung Lee
- Kyoung-Su Kim
- Wonmin Ko
- Gi-Sang Bae
- Sung-Joo Park
- Jun-Hyeog Jang
- Hyuncheol Oh
- Youn-Chul Kim
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Affiliations: Department of Biomedical Chemistry, College of Health and Biomedical Science, Konkuk University, Chungju 380-701, Republic of Korea, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea, College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 570-749, Republic of Korea, Department of Biochemistry, Inha University School of Medicine, Incheon 400-712, Republic of Korea
Published online on: December 7, 2015 https://doi.org/10.3892/ijmm.2015.2424
Pages: 475-484

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Abstract

Dojuksan is a traditional herbal medicine used in Korea and China to treat urinary diseases. In the present study, we aimed to examine the anti-inflammatory effects of an ethanol solvent extract of Dojuksan and a fraction (by bioassay-guided fractionation) derived from this extract, and to elucidate the specific mechanisms involved. The Dojuksan 30% ethanol extract (DEE) had a more significant and potent anti-inflammatory effect than the Dojuksan water extract (DWE). DEE markedly inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), as well as nuclear factor-κB (NF-κB) binding activity. We found that the anti-inflammatory effects of DEE were mediated by the induction of nuclear factor E2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). To further explore the anti-inflammatory effects of DEE, we generated 6 different fractions of DEE. Of these, DEE-5 decreased the production of NO more significantly than the other fractions. DEE-5 also significantly decreased the expression of iNOS and COX-2, and the production of NO, PGE2, TNF-α and IL-1β. In addition, DEE-5 also significantly increased HO-1 levels; HO-1 significanlty contributed to the inhibitory effects of DEE-5 on the production of pro-inflammatory mediators. In this study, we determined whether the choice of extraction solvent affects the biological activity of Dojuksan, a traditional herbal formula. Our findings demonstrate that DEE and a fraction derived from this extract exerts anti-inflammatory effects through Nrf2‑dependent HO-1 expression, and that DEE may thus have greater potential therapeutic application than DWE.

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