Ohno Osamu, Ye Mao, Koyama Tomoyuki, Yazawa Kazunaga, Mura Emi, Matsumoto Hiroshi, Ichino Takao, Yamada Kaoru, Nakamura Kazuhiko, Ohno Tomohiro, Yamaguchi Kohji, Ishida Junji, Fukamizu Akiyoshi, Uemura Daisuke
Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8602, Japan.
Bioorg Med Chem. 2008 Aug 15;16(16):7843-52. doi: 10.1016/j.bmc.2008.03.056. Epub 2008 Mar 27.
Hypertension is a lifestyle-related disease which often leads to serious conditions such as heart disease and cerebral hemorrhage. Angiotensin II (Ang II) plays an important role in regulating cardiovascular homeostasis. Consequently, antagonists that block the interaction of Ang II with its receptors are thought to be effective in the suppression of hypertension. In this study, we searched for plant compounds that had antagonist-like activity toward Ang II receptors. From among 435 plant samples, we found that EtOH extract from the resin of sweet gum Liquidambar styraciflua strongly inhibited Ang II signaling. We isolated benzyl benzoate and benzyl cinnamate from this extract and found that those compounds inhibited the function of Ang II in a dose-dependent manner without cytotoxicity. An in vivo study showed that benzyl benzoate significantly suppressed Ang II-induced hypertension in mice. In addition, we synthesized more than 40 derivatives of benzyl benzoate and found that the meta-methyl and 3-methylbenzyl 2'-nitrobenzoate derivatives showed about 10-fold higher activity than benzyl benzoate itself. Thus, benzyl benzoate, its derivatives, and benzyl cinnamate may be useful for reducing hypertension.
