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Soluble epoxide hydrolase inhibitory activity by rhizomes of Kaempferia parviflora Wall. ex Baker

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Abstract

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the rhizomes of Kaempferia parviflora Wall. ex Baker (Zingiberaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of dichloromethane fraction of K. parviflora rhizomes, we isolated sixteen compounds (1–16), including flavonoid derivatives (1–12), anthraquinones (13 and 14), triterpene (15), and triterpene glycoside (16). The structures of the isolated compounds were established in an extensive 1D and 2D NMR, as well as MS analysis. The sEH inhibitory activities of all isolated compounds were evaluated. Among the isolated flavonoid derivatives, 4, 6, 8, 10, and 12 were identified as potent inhibitors of sEH, with IC50 values ranging from 0.9 ± 0.1 to 4.5 ± 0.1 μM. In addition, a kinetic analysis of the flavonoid derivatives (1–12) revealed that the inhibitory activity of flavonoid derivatives 1–4 and 6–12 is mixed with K i values ranging from 0.1 ± 0.0 to 14.3 ± 0.3 μM, whereas compound 8 was a non-competitive with K i = 0.3 ± 0.0 μM. These findings suggest that flavonoid derivatives from K. parviflora rhizomes are potential novel sEH inhibitors.

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Abbreviations

AUDA:

12-(3-Adamantan-1-yl-ureido)-dodecanoic acid

DHETs:

Dihydroxyeicosatrienoic acids

EETs:

Epoxyeicosatrienoic acids

PHOME:

3-Phenyl-cyano(6-methoxy-2-naphthalenyl)methyl ester-2-oxiraneacetic acid

sEH:

Soluble epoxide hydrolase

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Acknowledgments

This study was supported by the Priority Research Center Program (2009–0093815) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology, Republic of Korea. The authors are grateful to Ok Nam Kim for the sample gift.

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Authors and Affiliations

  1. College of Pharmacy, Chungnam National University, Daejeon, 305–764, Republic of Korea

    Nguyen Phuong Thao, Bui Thi Thuy Luyen, Jang Hoon Kim, Ah Reum Jo, Seo Young Yang & Young Ho Kim

  2. Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18-Hoang Quoc Viet, Nghiado, Caugiay, Hanoi, Vietnam

    Nguyen Phuong Thao, Nguyen Tien Dat & Chau Van Minh

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  1. Nguyen Phuong Thao
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  2. Bui Thi Thuy Luyen
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Correspondence to Young Ho Kim.

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Thao, N.P., Luyen, B.T.T., Kim, J.H. et al. Soluble epoxide hydrolase inhibitory activity by rhizomes of Kaempferia parviflora Wall. ex Baker. Med Chem Res 25, 704–711 (2016). https://doi.org/10.1007/s00044-016-1525-y

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