Inhibitory effects of hydroxylated cinnamoyl esters on lipid absorption and accumulation

  • Bioorg Med Chem. 2015 Jul 1;23(13):3788-95. doi: 10.1016/j.bmc.2015.03.086.
Masahiko Imai  1 ,  Takaya Kumaoka  1 ,  Makiko Hosaka  1 ,  Yui Sato  1 ,  Chuan Li  1 ,  Masashi Sudoh  2 ,  Yoshiko Tamada  2 ,  Hiromasa Yokoe  2 ,  Setsu Saito  2 ,  Masayoshi Tsubuki  2 ,  Noriko Takahashi  3
Affiliations
  • 1. Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
  • 2. Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
  • 3. Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. Electronic address: [email protected].
PMID: 25910587 DOI: 10.1016/j.bmc.2015.03.086
Abstract

Obesity is a risk factor associated with several lifestyle-related diseases, for example, diabetes, high blood pressure, hyperlipidemia and Cancer. Caffeic acid 2-phenylethyl ester (CAPE, 1), a naturally-occurring compound found in various Plants and propolis, which exhibits anti-inflammatory, immunomodulatory and cytotoxic activities and inhibits 3T3-L1 differentiation to adipocytes. As part of our efforts to moderate lifestyle-related diseases, we synthesized analogs of 1 and studied their effects on pancreatic Lipase activities, lipid absorption, and 3T3-L1 differentiation. We found that catechols 1-4 show inhibitory activities against pancreatic Lipase in a dose-dependent manner in vitro. Compounds 1-3 proved to be more potent inhibitors of pancreatic Lipase than 5, 6, 8, and 9, which have one hydroxyl group, respectively. Compound 7 has three aromatic hydroxyl groups and restrains greater Lipase inhibitory activity than the Other compounds. In addition, 7 and 3 significantly suppress a rise in blood triglyceride (TG) levels in mice given corn oil orally. Furthermore, 2 and 3 are more potent at preventing 3T3-L1 differentiation (lipid accumulation) than 1, while 7 is more potent than 3, 8, and 9 in these assays. Compounds 2, 3, and 7 inhibit lipid absorption and accumulation, with new compound 7 being the most potent. These results indicate that 7 may have potential benefits as a health agent with anti-obesity properties.

Keywords
Anti-obesity; Caffeic acid phenylethyl ester; Lipase; Lipid absorption; Lipid accumulation.
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