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

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.

Metabolomics Analysis Reveals the Differences Between Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd.

“…In our study, we found significantly increased amounts of saponarin, prunetin, 3- O -acetylpinobanksin, methylhesperidin, and other flavonoids in BsR than in BcR. Saponarin, which is the sole flavonoid present in barley sprout leaves ( Kim et al, 2022 ), possesses potent antioxidant ( Kamiyama and Shibamoto, 2012 ) and hepatoprotective activities ( Simeonova et al, 2013 ), and can be potentially used to prevent and relieve immune-related skin diseases ( Min et al, 2021 ). Prunetin has anti-inflammatory effects ( Abusaliya et al, 2022 ), prevents hepatocellular carcinogenesis by improving functions of the liver ( Li G. et al, 2022 ), and suppresses high-fat diet (HFD)-induced adipogenesis in the liver tissues of mice by regulating gene expression in liver tissue ( Ahn et al, 2013 ).…”

Daphnetin contributes to allergen-induced Th2 cytokine expression and type 2-immune responses in atopic dermatitis and asthma

“…The β-hexosaminidase release was chosen as the index of degranulation. 20,21 As shown in Fig. 9B, the β-hexosaminidase release was inhibited after adding Dap., and the inhibitory effects were expressed dose-dependently by Dap.…”

“…The signaling cascade activation regulates the degranulation and production of allergic and inflammatory cytokines. 21 The inhibitory effect on the degranulation of antigen-stimulated RBL-2H3 cells was investigated. The β-hexosaminidase release was determined as an index of degranulation.…”

Extraction and Fractionation of Bioactives from Dipsacus fullonum L. Leaves and Evaluation of Their Anti-Borrelia Activity

“…Although flavonoids such as apigenin and luteolin have shown to be cytotoxic, their glycosides were much less so [23]. Previously, the phenolic extracts from D. sativus containing saponarin, isoorientin and isovitexin have been proven to reveal antioxidant activities [17], and moreover, saponarin has been recently shown to possess anti-inflammatory and anti-allergic effects [24]. The other main constituents were chlorogenic acid (NP8) and dichlorogenic acid isomers (NP7).…”