Anti-Inflammatory and Anti-Allergic Effects of Saponarin and Its Impact on Signaling Pathways of RAW 264.7, RBL-2H3, and HaCaT Cells

Saponarin{5-hydroxy-2-(4-hydroxyphenyl)-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one}, a flavone found in young green barley leaves, is known to possess antioxidant, antidiabetic, and hepatoprotective effects. In the present study, the anti-inflammatory, anti-allergic, and skin-protective effects of saponarin were investigated to evaluate its usefulness as a functional ingredient in cosmetics. In lipopolysaccharide-induced RAW264.7 (murine macrophage) cells, saponarin (80 mu M) significantly inhibited cytokine expression, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, inducible nitric oxide synthase, and cyclooxygenase (COX)-2. Saponarin (80 mu M) also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 involved in the mitogen-activated protein kinase signaling pathway in RAW264.7 cells. Saponarin (40 mu M) significantly inhibited beta-hexosaminidase degranulation as well as the phosphorylation of signaling effectors (Syk, phospholipase C gamma 1, ERK, JNK, and p38) and the expression of inflammatory mediators (tumor necrosis factor [TNF]-alpha, IL-4, IL-5, IL-6, IL-13, COX-2, and Fc epsilon RI alpha/gamma) in DNP-IgE- and DNP-BSA-stimulated RBL-2H3 (rat basophilic leukemia) cells. In addition, saponarin (100 mu M) significantly inhibited the expression of macrophage-derived chemokine, thymus and activation-regulated chemokine, IL-33, thymic stromal lymphopoietin, and the phosphorylation of signaling molecules (ERK, p38 and signal transducer and activator of transcription 1 [STAT1]) in TNF-alpha- and interferon (IFN)-gamma-stimulated HaCaT (human immortalized keratinocyte) cells. Saponarin (100 mu M) also significantly induced the expression of hyaluronan synthase-3, aquaporin 3, and cathelicidin antimicrobial peptide (LL-37) in HaCaT cells, which play an important role as skin barriers. Saponarin remarkably inhibited the essential factors involved in the inflammatory and allergic responses of RAW264.7, RBL-2H3, and HaCaT cells, and induced the expression of factors that function as physical and chemical skin barriers in HaCaT cells. Therefore, saponarin could potentially be used to prevent and relieve immune-related skin diseases, including atopic dermatitis.

Automated summary

Saponarin, a flavone found in young green barley leaves, demonstrates anti-inflammatory, anti-allergic, and skin-protective effects, making it a potential functional ingredient in cosmetics. Its inhibitory effects on cytokine expression and signaling pathways in different types of cells suggest utility in preventing and treating immune-related skin diseases like atopic dermatitis.