title: Inhibitory effects of hydroxylated cinnamoyl esters on lipid absorption and accumulation.
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.
authors.affiliation: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Imai
authors.affiliation: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Kumaoka
authors.affiliation: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Hosaka
authors.affiliation: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sudoh
authors.affiliation: Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tamada
authors.affiliation: Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yokoe
authors.affiliation: Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Setsu
authors.initials: S
authors.lastname: Saito
authors.affiliation: Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tsubuki
authors.affiliation: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. Electronic address: t-noriko@hoshi.ac.jp.
authors.forename: Noriko
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D002396:Catechols / Q000138:chemical synthesis / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003314:Corn Oil / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D007408:Intestinal Absorption / Q000187:drug effects*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D019440:Anti-Obesity Agents; D002109:Caffeic Acids; D002396:Catechols; D014280:Triglycerides; D003314:Corn Oil; D008049:Lipase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: Anti-obesity; Caffeic acid phenylethyl ester; Lipase; Lipid absorption; Lipid accumulation