Effects of Osthol Isolated from Cnidium monnieri Fruit on Urate Transporter 1

Molecules

Hirotaka Matsuo¹  Yuusuke Tashiro²  Toshiaki Makino²  Ryo Sakai²  Hiroshi Suzuki³  Tappei Takada³  Yukio Kato⁴  Tomoko Hirose-Sugiura⁴ 

[1] Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan;Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan;Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan;Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan;

关键词: urate transporter 1;    uric acid;    traditional Japanese Kampo medicine;    Cnidium monnieri;    osthol;    coumarins;   

DOI  :  10.3390/molecules23112837

来源: DOAJ

【 摘 要 】

(1) Background: Crude drugs used in traditional Japanese Kampo medicine or folk medicine are major sources of new chemical entities for drug discovery. We screened the inhibitory potential of these crude drugs against urate transporter 1 (URAT1) to discover new drugs for hyperuricemia. (2) Methods: We prepared the MeOH extracts of 107 different crude drugs, and screened their inhibitory effects on URAT1 by measuring the uptake of uric acid by HEK293/PDZK1 cells transiently transfected with URAT1. (3) Results: We found that the extract of the dried mature fruit of Cnidium monnieri inhibited urate uptake via URAT1. We isolated and identified osthol as the active ingredient from this extract. Osthol noncompetitively inhibited URAT1 with an IC₅₀ of 78.8 µM. We evaluated the effects of other coumarins and found that the prenyl group, which binds at the 8-position of coumarins, plays an important role in the inhibition of URAT1. (4) Conclusions: Cnidium monnieri fruit may be useful for the treatment of hyperuricemia or gout in traditional medicine, and its active ingredient, osthol, is expected to be a leading compound for the development of new drugs for hyperuricemia.

【 授权许可】

Unknown