2. Academic Validation
  3. Inhibition of cholesteryl ester synthesis by polyacetylenes from Atractylodes rhizome

Inhibition of cholesteryl ester synthesis by polyacetylenes from Atractylodes rhizome

  • Bioorg Med Chem Lett. 2020 Apr 1;30(7):126997. doi: 10.1016/j.bmcl.2020.126997.
Elyza Aiman Azizah Nur 1,  Taichi Ohshiro 2,  Keisuke Kobayashi 3,  Jing Wu 4,  Elly Wahyudin 5,  Huiping Zhang 6,  Fumiaki Hayashi 6,  Hirokazu Kawagishi 4,  Hiroshi Tomoda 7
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Faculty of Pharmacy, Hasanuddin University, Perintis Kemerdekaan Tamalanrea, Makassar 90245, South Sulawesi, Indonesia.
  • 2 Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: tohshiro@med.nagoya-u.ac.jp.
  • 3 Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
  • 4 Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan.
  • 5 Faculty of Pharmacy, Hasanuddin University, Perintis Kemerdekaan Tamalanrea, Makassar 90245, South Sulawesi, Indonesia.
  • 6 NMR Science and Development Division, RIKEN Spring-8 Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • 7 Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: tomodah@pharm.kitasato-u.ac.jp.
PMID: 32035699 DOI: 10.1016/j.bmcl.2020.126997
Abstract

Using activity guided purification, four known compounds, sesquiterpene atractylenolide III (1), and the polyacetylenes 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol (2), 14-acetoxy-12-α-methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol (3), and 14-acetoxy-12-β -methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol (4), were isolated from a traditional herbal medicine, Atractylodes rhizome. Structurally similar 3 and 4 (3/4 mixture) were obtained as a mixture. In intact Chinese hamster ovary (CHO) K1 cell assays, 1, 2, and a 3/4 mixture selectively inhibited Cholesterol [14C]oleate synthesis from [14C]oleate with IC50 values of 73.5 µM, 35.4 µM, and 10.2 µM, respectively, without any effects on cytotoxicity. As a potential target of these inhibitors involved in cholesteryl ester (CE) synthesis, effects on sterol O-acyltransferase (SOAT) activity were investigated using microsomes prepared from CHO-K1 cells as an Enzyme source. Hence, these compounds inhibit SOAT activity with IC50 values (211 µM for 1, 29.0 µM for 2, and 11.8 µM for 3/4 mixture) that correlate well with those measured from intact cell assays. Our results strongly suggest that these compounds inhibit CE synthesis by blocking SOAT activity in CHO-K1 cells.

Keywords

Cholesteryl ester synthesis; Inhibitor; Polyacetylene; Sesquiterpene; Sterol O-acyltransferase.

Figures