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Calycosin and formononetin from astragalus root enhance dimethylarginine dimethylaminohydrolase 2 and nitric oxide synthase expressions in Madin Darby Canine Kidney II cells

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Abstract

Nitric oxide (NO) is a crucial vasodilator produced by nitric oxide synthase (NOS). Asymmetric dimethylarginine (ADMA) is an endogenous NOS inhibitor and mainly catabolized by dimethylarginine dimethylaminohydrolase (DDAH). As we reported, the antihypertensive effect of shichimotsukokato (SKT), a formula of Japanese traditional kampo medicine consisting of 7 crude drugs, in 5/6 nephrectomized rats, is mediated by the DDAH-ADMA-NO pathway. Our present study aimed to explore the effective compounds of SKT using Madin Darby Canine Kidney (MDCK) II cells. We isolated two isoflavones, calycosin and formononetin from astragalus root, one of the components of SKT, which can promote DDAH2 protein and mRNA expressions in MDCK II cells. The neuronal NOS levels were also upregulated by the treatment of calycosin and formononetin. These results suggest that calycosin and formononetin could be the active ingredients of astragalus root and SKT that cause antihypertensive effects. The increased levels of DDAH2 and NOS may enhance NO production, decrease ADMA level and improve endothelial and cardiovascular dysfunction.

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Acknowledgments

This research was supported by Grants-in-Aid for Scientific Research (KAKENHI) C, #21590172 (2009).

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Authors and Affiliations

  1. Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan

    Fan Bai, Toshiaki Makino, Keiko Kono, Takahiko Ono & Hajime Mizukami

  2. College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, 463-8521, Japan

    Akito Nagatsu

  3. Atami Hospital, International University of Health and Welfare, 13-1 Higashi-kaigan-cho, Atami, 413-0012, Japan

    Takahiko Ono

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  1. Fan Bai
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  2. Toshiaki Makino
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  6. Hajime Mizukami
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Correspondence to Toshiaki Makino.

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Bai, F., Makino, T., Kono, K. et al. Calycosin and formononetin from astragalus root enhance dimethylarginine dimethylaminohydrolase 2 and nitric oxide synthase expressions in Madin Darby Canine Kidney II cells. J Nat Med 67, 782–789 (2013). https://doi.org/10.1007/s11418-013-0749-0

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