Dehydrodiconiferyl alcohol suppresses monocyte adhesion to endothelial cells by attenuation of JNK signaling pathway.
Several clinical studies have shown that the intake of aged garlic extract improves endothelial dysfunction. Lignan compounds, (+)-(2S,3R)-dehydrodiconiferyl alcohol (DDC) and (-)-(2R,3S)-dihydrodehydrodiconiferyl alcohol (DDDC), have been isolated as antioxidants in aged garlic extract. There is evidence showing the importance of oxidative stress in endothelial dysfunction. In the present study, we examined whether DDC and DDDC enhance endothelial cell function in vitro. Cell adhesion assay was performed using THP-1 monocyte and human umbilical vein endothelial cells (HUVECs) which were activated by lipopolysaccharide (LPS) or advanced glycation end products (AGEs)-BSA. Cellular ELISA method was used for the evaluation of vascular cell adhesion molecule 1 (VCAM-1) expression on HUVECs. DDC and DDDC suppressed the adhesion of THP-1 to HUVECs which was activated by LPS or AGEs-BSA. DDC and DDDC also inhibited VCAM-1 expression induced by LPS or AGEs-BSA, but DDDC was less effective than DDC. In addition, the inhibitory effect of DDC on VCAM-1 expression involved suppressing JNK/c-Jun pathway rather than NF-κB pathway. DDC has an inhibitory effect on VCAM-1 expression via JNK pathway in endothelial cells and therefore may serve as a novel pharmacological agent to improve endothelial dysfunction.
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co. Ltd., 1624 Shimokotachi, Kodacho, Akitakata, Hiroshima 739-1195, Japan. Electronic address: tsuneyoshi_td@wakunaga.co.jp.
Tadamitsu
T
Tsuneyoshi
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co. Ltd., 1624 Shimokotachi, Kodacho, Akitakata, Hiroshima 739-1195, Japan. Electronic address: kanamori_y@wakunaga.co.jp.
Yuta
Y
Kanamori
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co. Ltd., 1624 Shimokotachi, Kodacho, Akitakata, Hiroshima 739-1195, Japan. Electronic address: Matsutomo_t@wakunaga.co.jp.
Toshiaki
T
Matsutomo
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co. Ltd., 1624 Shimokotachi, Kodacho, Akitakata, Hiroshima 739-1195, Japan. Electronic address: morihara_n@wakunaga.co.jp.
Naoaki
N
Morihara
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D010636:Phenols / Q000008:administration & dosage*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D010636:Phenols; D019010:Vascular Cell Adhesion Molecule-1; C080686:dehydrodiconiferyl alcohol
Advanced glycation end products; Aged garlic extract; Dehydrodiconiferyl alcohol; JNK pathway; Lignans; VCAM-1