4'‑O‑Methylalpinumisoflavone inhibits the activation of monocytes/macrophages to an immunostimulatory phenotype induced by 27‑hydroxycholesterol

Lee,Jeonga; Kim,Bo   Young; Son,Yonghae; Giang,Do   Hoang; Lee,Dongho; Eo,Seong‑Kug; Kim,Koanhoi

doi:10.3892/ijmm.2019.4135

4'‑O‑Methylalpinumisoflavone inhibits the activation of monocytes/macrophages to an immunostimulatory phenotype induced by 27‑hydroxycholesterol

Authors:
- Jeonga Lee
- Bo Young Kim
- Yonghae Son
- Do Hoang Giang
- Dongho Lee
- Seong‑Kug Eo
- Koanhoi Kim
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Affiliations: Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 50612, Republic of Korea, Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea, College of Veterinary Medicine and Bio‑Safety Research Institute, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea
Published online on: March 18, 2019 https://doi.org/10.3892/ijmm.2019.4135
Pages: 2177-2186

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Abstract

The epidemiological, animal and cell effects of plant metabolites suggest versatile health benefits of flavonoids. However, whether flavonoids affect the deleterious biological activity of oxygenated cholesterol molecules remains to be elucidated. The present study investigated the effects of 4'‑O‑methylalpinumisoflavone (mAI) isolated from Maclura tricuspidata (Cudrania tricuspidata) on the 27‑hydroxycholesterol (27OHChol)‑induced activation of monocytes/macrophages using human THP‑1 cells. mAI dose‑dependently impaired the expression of C‑C motif chemokine ligand (CCL)2 chemokine and the migration of monocytic cells enhanced by 27OHChol. mAI downregulated the surface and cellular levels of CD14 and inhibited the release of soluble CD14. This isoflavone significantly weakened the lipopolysaccharide responses that were enhanced in the presence of 27OHChol, and inhibited the transcription and secretion of the active gene product of matrix metalloproteinase‑9. mAI also suppressed the expression of C‑C motif chemokine receptor 5 ligands, including CL3 and CCL4, and M1‑phenotype markers induced by 27OHChol. Furthermore, mAI impaired phosphorylation of the nuclear factor‑κB p65 subunit without affecting the phosphorylation of Akt. These results indicate that mAI inhibits the activation of monocytes/macrophages to the immunostimulatory phenotype in a milieu rich in 27OHChol, suggesting potential benefits of the flavonoid for the treatment of diseases in which the pathogenesis is linked to 27OHChol‑induced inflammatory responses.

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