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Coumarins from Angelica decursiva inhibit lipopolysaccharide-induced nitrite oxide production in RAW 264.7 cells

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Abstract

Angelica decursiva has long been used in Korean traditional medicine as an antitussive, analgesic, antipyretic, and cough remedy. In this study, the anti-inflammatory activity of 9 coumarin derivatives isolated from a 90 % methanol fraction was evaluated via inhibition of production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Among the tested compounds, edulisin II (1) exhibited the most potent NO production inhibitory activity, followed by decursidin (2), Pd–C-III (3), 4-hydroxy Pd–C-III (4), Pd–C-I (5), and Pd–C-II (6). In contrast, (+)-trans-decursidinol (7) did not exhibit NO suppressive effects on LPS-stimulated RAW 264.7 cells. Structure-activity relationships revealed that esterification of the hydroxyl at C-3′ or C-4′ of 7 with an angeloyl/senecioyl/acetyl group is essential for its inhibitory activity against NO production, while the number of angeloyl or senecioyl groups, and their positions greatly affect the potency of these coumarins. Coumarins 1-6 also inhibited TNF-α production and iNOS protein expression, while compounds 1-4 inhibited COX-2 protein expression in LPS-stimulated RAW 264.7 cells. These results suggest that coumarins isolated from A. decursiva might be used as potential leads for the development of therapeutic agents for inflammation-associated disorders.

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2014R1A1A3051684 and 2012R1A6A1028677).

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Authors and Affiliations

  1. Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea

    Ishrat Jahan Ishita & Jae Sue Choi

  2. Department of Pharmacy, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902, Bangladesh

    Md. Nurul Islam

  3. College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea

    Yeong Shik Kim

  4. Angiogenesis & Chinese Medicine Laboratory, Department of Pharmacology, University of Cambridge, Cambridge, UK

    Ran Joo Choi

  5. Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea

    Hee Sook Sohn & Hyun Ah Jung

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  1. Ishrat Jahan Ishita
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Correspondence to Hyun Ah Jung or Jae Sue Choi.

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Ishita, I.J., Nurul Islam, M., Kim, Y.S. et al. Coumarins from Angelica decursiva inhibit lipopolysaccharide-induced nitrite oxide production in RAW 264.7 cells. Arch. Pharm. Res. 39, 115–126 (2016). https://doi.org/10.1007/s12272-015-0668-6

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