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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