Abstract
Ligation of the receptor for advanced glycation end products (RAGE) is critical for monocyte activation involved in diabetic inflammation. In this study, the effects of the geranyl flavonoid derivatives (6-geranyl-7,4′-dihydroxyflavanone, AC-1; 4,2′,4′-trihydroxy-3′-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone, AC-2; 3,4,2′,4′-tetrahydroxy-3′-geranyldihydrochalcone, AC-3; 4,2′,4′-trihydroxy-5′-geranyldihydrochalcone, AC-4) isolated from the fruit of Artocarpus communis (breadfruit) on the human THP-1 monocyte (THP-1) activation stimulated by S100B, a ligand of RAGE, were evaluated. The morphology of S100B-induced THP-1, which may be essential for the elucidation of the functional role of S100B in monocyte activation was investigated. We also directly demonstrated that S100B-induced THP-1 exhibited the morphological characteristics of inflammation, which were inhibited by the addition of AC-2, AC-3 or AC-4. Moreover, AC-2, AC-3 or AC-4 inhibited S100B-induced ROS generation, mRNA expression of inflammatory mediators (COX-2, TNF-α, IL-6 and RAGE) and IL-6 secretion. Thus, geranyl flavonoid derivatives of breadfruit may have potent implications to prevent diabetic inflammation.
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