Abstract
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 μM) significantly inhibited cytokine expression, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, inducible nitric oxide synthase, and cyclooxygenase (COX)-2. Saponarin (80 μM) 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 μM) significantly inhibited β-hexosaminidase degranulation as well as the phosphorylation of signaling effectors (Syk, phospholipase Cγ1, ERK, JNK, and p38) and the expression of inflammatory mediators (tumor necrosis factor [TNF]-α, IL-4, IL-5, IL-6, IL-13, COX-2, and FcεRIα/γ) in DNP-IgE- and DNP-BSA-stimulated RBL-2H3 (rat basophilic leukemia) cells. In addition, saponarin (100 μM) 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-α- and interferon (IFN)-γ-stimulated HaCaT (human immortalized keratinocyte) cells. Saponarin (100 μM) 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.
Highlights
Protein was significantly decreased by saponarin. These results suggest that saponarin can modulate the expression of T helper 2 cells (Th2) chemokines (MDC and TARC) and cytokines (IL-33 and Thymic stromal lymphopoietin (TSLP)) in tumor necrosis factor (TNF)-α- and IFN-γ-stimulated HaCaT cells
Previous studies reported that the JAK/STAT (Janus tyrosine kinase/signal transducers and activators of transcription) signaling pathway, along with mitogen-activated protein protein kinase kinase (MAPK), is involved in the production of TARC and MDC in TNF-α- and IFN-γ-stimulated HaCaT cells [12,16]
We evaluated the effects of saponarin on the factors associated with inflammation, allergy, and atopic dermatitis (AD) in RAW264.7, RBL-2H3, and HaCaT cells
Summary
In RAW264.7 cells, inducible nitric oxide synthase (iNOS) is expressed by stimuli such as lipopolysaccharides (LPS), cytokines, and bacterial toxins, inducing nitric oxide (NO) production, which plays an important role in the immune response [27,28,29]. TNF-α plays an important role in inducing the inflammatory response and inducing the expression of pro-inflammatory cytokines, and IL-6 is a crucial inflammatory mediator secreted by LPS [31,32]. In order to utilize natural resources in various fields such as functional foods, medicines, and cosmetics, determining the physiological activities and mechanisms of the main ingredients contained in the resources is essential. In this study, we investigated the anti-inflammatory and anti-allergic effects of saponarin, the main component of barley sprouts, as well as the effects on factors related to AD. We believe that the detailed mechanism of saponarin identified in this study provides a fundamental basis for various future uses of this flavonoid
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