2. Academic Validation
  3. Inhibitory effects of hydroxylated cinnamoyl esters on lipid absorption and accumulation

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

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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