Two novel ligans isolated from the Saururus chinensis and their anti-inflammatory effects by activation of Nrf2 and HO-1

Extracts of Saururus chinenesis were shown to have an anti-inflammatory effect by inhibition of nitric oxide in RAW264.7 cells. In our ongoing program to identify anti-inflammatory agents, bioassay-guided fractionation led to the isolation of two novel lignans (1 and 2) and six known lignans (3-8). Their chemical structures were elucidated by combination of spectroscopic methods and semi-synthesis [1,2]. Compounds 2 and 8 inhibited lipopolysaccharide (LPS)-induced production of NO with IC₅₀ values of 5.8 and 1.5µM, 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 administration of 2 and 8. These lignans (2 and 8) induced the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Treatments with 2 and 8 in RAW264.7 cells also induced nuclear translocation of nuclear-E2-related factor 2 (Nrf2), a key regulator of HO-1 protein expression [3]. In our study, lignans exerted anti-inflammatory effects in RAW264.7 cells through the Nrf2/HO-1 pathway, and may be potential HO-1 inducers for preventing or treating inflammation.

Acknowledgements: This research was supported by the Traditional Medicine R&D Program funded by the Ministry of Health & Welfare through the Korea Health industry Development Institute (2015-KDUDU-010).

Keywords: Saururus chinensis, 4-O-demethylmanassantin B, manassantin A, Mosher's method.

References:

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