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Lignans from Saururus chinensis exhibit anti-inflammatory activity by influencing the Nrf2/HO-1 activation pathway

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Abstract

As part of our ongoing program to develop anti-inflammatory agents, an extract derived from Saururus chinensis collected in Korea was found to inhibit nitric oxide (NO) production in RAW264.7 cells. Bioassay-guided fractionation led to the isolation two new (1 and 2) and six known dineolignans (3–8). To the best of our knowledge, manassatin B1 (3) was isolated from S. chinensis for the first time. All structures were elucidated using extensive spectroscopic analysis. Of these compounds, 2 and 8 inhibited lipopolysaccharide (LPS)-induced production of NO and showed IC50 values of 5.80 and 1.52 µM, respectively. LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) was also significantly suppressed by the administration of 2 and 8. In addition, these lignans induced the expression of heme oxygenase-1 (HO-1) in a concentration-dependent manner. Nuclear translocation of nuclear-E2-related factor 2 (Nrf2), a key regulator of HO-1 protein expression, was also induced in RAW264.7 cells treated with 2 and 8. These findings suggested that these lignans exerted anti-inflammatory effects in RAW264.7 cells through modulation of the Nrf2/HO-1 pathway and that they were potential HO-1 inducers for preventing or treating inflammation.

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Acknowledgements

This research was supported by the National Research Foundation of Korea (NRF-2016R1D1A1B03930246) by the Ministry of Education, Korea. We are grateful to the Korea Basic Science Institute (KBSI) for mass spectrometric measurements.

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Authors and Affiliations

  1. College of Pharmacy, Drug Research and Development Center, Daegu Catholic University, Gyeongbuk, 712-702, Republic of Korea

    Yeon Woo Jung, Bo Mi Lee, Manh Tuan Ha, Manh Hung Tran, Mi Hee Woo & Byung Sun Min

  2. College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 702-701, Republic of Korea

    Jeong Ah Kim

  3. Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do, 200-701, Republic of Korea

    Suhyun Lee & Jeong Hyung Lee

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  1. Yeon Woo Jung
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Jung, Y.W., Lee, B.M., Ha, M.T. et al. Lignans from Saururus chinensis exhibit anti-inflammatory activity by influencing the Nrf2/HO-1 activation pathway. Arch. Pharm. Res. 42, 332–343 (2019). https://doi.org/10.1007/s12272-018-1093-4

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