Studies on lymphangiogenesis inhibitors from Korean and Japanese crude drugs

Dami Jeong, Kousuke Watari, Takayuki Shirouzu, Mayumi Ono, Keiichi Koizumi, Ikuo Saiki, Youn Chul Kim, Chiaki Tanaka, Ryuichi Higuchi, Tomofumi Miyamoto

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Metastasis occurs when cancer cells detach from a tumor, travel to distant sites in the body and develop into tumors in these new locations. Most cancer patients die from metastases. Among the various forms of cancer metastasis, lymphatic metastasis is an important determinant in cancer treatment and staging. In this study, we investigated lymphangiogenesis inhibitors from crude drugs used in Japan and Korea. The three crude drugs Saussureae Radix, Psoraleae Semen and Aurantti Fructus Immaturus significantly inhibited the proliferation of temperature-sensitive rat lymphatic endothelial (TR-LE) cells in vitro. By a chromatographic method using bioassay-guided fractionation methods, costunolide (1) and dehydrocostus lactone (2) from S. Radix, p-hydroxybenzaldehyde (3), psoralen (4), angelicin (5), psoracorylifol D (6), isobavachalone (7), bavachinin (8) Δ3,2-hydroxybakuchiol (9) and bakuchiol (10) from P. Semen and cis-octadecyl ferulate (11), (2R)-3β,7,4′- trihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (12), (2S)-7,4′-dihydroxy-5-methoxy-8-( γ,γ-dimethylallyl)-flavanone (13) and umbelliferone (14) from A. F. Immaturus were obtained. Three compounds (compounds 11-13) from A. F. Immaturus were isolated for the first time from this medicinal plant. Among isolated compounds, ten compounds (compounds 1, 2, 6-12, 13) showed an inhibitory effect on the proliferation and the capillary-like tube formation of TR-LE cells. In addition, all compounds except compound 12 showed selective inhibition of the proliferation of TR-LE cells compared to Hela and Lewis lung carcinoma (LLC) cells. These compounds might offer clinical benefits as lymphangiogenesis inhibitors and may be good candidates for novel anti-cancer and anti-metastatic agents.

Original languageEnglish
Pages (from-to)152-157
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Issue number1
Publication statusPublished - Jan 2013

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science


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