Natural flavone kaempferol suppresses chemokines expression in human monocyte THP-1 cells through MAPK pathways

There is increasing evidence that daily intake of flavonoids reduced severity and prevalence of allergic diseases. However, the mechanism of its antiinflammatory effects in allergic diseases remains uncertain. Kaempferol, which belongs to the flavone group, is a strong antioxidant among natural flavonoids and is the essential component of many beverages and vegetables. Because chemokine is one of the key mediators in allergic inflammatory process, we investigated the effect of kaempferol on chemokines expression in monocytes. Our data demonstrated that kaempferol significantly inhibited the lipopolysaccharide (LPS)-induced production of monocyte-derived chemokine (MDC), interferon gamma-induced protein 10 (IP-10), and interleukin-8 (IL-8) in THP-1 cells. Growth-related oncogene-α (GRO-α) was also suppressed at a higher concentration. We also found that kaempferol was able to suppress LPS-induced mitogen-activated protein kinase (MAPK) pathways, as well as the phosphorylation of upstream c-raf and MEK1/2. In brief, kaempferol suppressed LPS-induced T helper 1 (Th1), T helper 2 (Th2), and neutrophil-related chemokines production in monocytes might be via the MAPK pathways.     

Monocyte Differentiation-Surveilling Nano-Shuttles for Activatable Targeted Inhibition of Atherosclerotic Plaque Progression

Atherosclerosis can form intimal plaques in the arteries and undergo plaque rupture with followed stroke or myocardial infarction under certain pathological conditions. However, suboptimal intraplaque accumulation, along with severe off-target effects, remain formidable obstacles for efficient pharmacotherapy of atherosclerosis. A characteristic feature of the progression of atherosclerosis is the continuous recruitment of inflammatory monocytes that differentiate into foamy macrophages with the generation of legumain in the plaques. In this study, a bio-activatable nano-shuttle based on human serum albumin is conceived that contained curcumin to allow the precise inhibition of atherosclerosis progression. Following intravenous injection, the nano-shuttles are almost exclusively engulfed by inflammatory monocytes in an efferocytosis-mimetic manner and selectively co-migrated with the monocytes towards the plaques. The nano-shuttles are readily activated to release the initially arrested curcumin in response to the generation of legumain upon the differentiation of monocytes into foamy macrophages within the plaques. Treatment assessments on atheroprone apolipoprotein-E-deficient mice indicated that the nano-shuttles substantially inhibit the progression of atherosclerosis by attenuating the plaque inflammation burden without any obvious adverse effects. The integration of highly selective accumulation and specific drug activation of the nano-shuttles in plaques can arouse an advanced therapeutic strategy to prevent atherosclerotic cardiovascular disease.