Tithonia diversifolia-derived orizabin suppresses cell adhesion, differentiation, and oxidized LDL accumulation by Akt signaling suppression via PTEN promotion in THP-1 cells

Masahiro Ide, Izumi Yoshida, Momochika Kumagai, Takashi Mishima, Yushi Takahashi, Kazuhiro Fujita, Tomoji Igarashi, Eiji Matsuura

    Research output: Contribution to journalArticlepeer-review

    Abstract

    As a Japanese folk medicine, Tithonia diversifolia is used for cardiovascular disease prevention and health maintenance. We isolated T. diversifolia-derived orizabin based on the nitric oxide production inhibitory effect. This study aimed to consider orizabin as a novel functional compound with anti-atherosclerotic activity. Orizabin significantly inhibited the adhesion of THP-1 cells to human umbilical vein endothelial cells (HUVECs) and suppressed the mRNA expression of adhesion molecules in HUVECs. In Phorbol 12-myristate 13-acetate stimulated THP-1 cells, orizabin suppressed macrophage differentiation, CD36 expression (1% at 10 μM), and NFκB transcriptional activity. Furthermore, orizabin suppressed oxidized low-density lipoprotein (oxLDL) uptake in macrophages and the Akt phosphorylation. On the contrary, we revealed that phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN) mRNA and protein expression were promoted significantly by orizabin (mRNA, 270-fold at 10 μM). Our study presented the possibility that T. diversifolia-derived orizabin is novel anti-atherosclerotic compound via the suppression of Akt phosphorylation, and T. diversifolia may be effective as a new crop for vascular health maintenance. Practical applications: In this study, the differentiation of monocytes was suppressed without any toxicity, it was obvious in the image, and the oxLDL uptake in monocytes was clearly suppressed by orizabin. Our findings presented that T. diversifolia-derived compound orizabin specifically contributes to the promotion of PTEN expression and suppression of Akt signal in cells, and acts to suppress inflammation by suppression of NFκB transcriptional activity. As a component derived from food, it has a strong function and can be used to maintain the health for blood vessels. It is also a finding that deserves to expand production currently being carried out on a small scale. Furthermore, the promoting effect of PTEN known as a cancer suppressor in orizabin may result in further use for pharmaceuticals research. Orizabin can be safely used as a food-derived compound for maintaining human health.

    Original languageEnglish
    Article numbere13268
    JournalJournal of Food Biochemistry
    Volume44
    Issue number7
    DOIs
    Publication statusPublished - Jul 1 2020

    Keywords

    • Akt
    • PTEN
    • THP-1
    • Tithonia diversifolia
    • atherosclerosis
    • orizabin

    ASJC Scopus subject areas

    • Food Science
    • Biophysics
    • Pharmacology
    • Cell Biology

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