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 µM) significantly inhibited cytokine expression, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, 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 ß-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.

Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-Allergic, Anti-Inflammatory, and Skin-Protective Activities.

Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 µM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1ß, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase [iNOS]), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 µM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human ß-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.

Squamous cell carcinoma of head and neck: what internists should know.

Squamous cell carcinoma of head and neck (SCCHN) is a group of cancer arising from mucosal surfaces of the head and neck. Optimal management of SCCHN requires a multidisciplinary team of surgical oncologists, radiation oncologists, medical oncologists, nutritionist, and speech-language pathologists, due to the complexity of anatomical structure and importance of functional outcome. Human papilloma virus (HPV)-related SCCHN represents a distinct subset from HPV negative SCCHN which is associated with carcinogen exposure such as cigarette smoking, betel nut use and alcohol. HPV related SCCHN responds better to concurrent chemoradiation and has better overall prognosis, compared to HPV negative SCCHN. Radiation therapy has been introduced to the treatment of SCCHN, administered concurrently with systemic chemotherapy for locoregional SCCHN, as well as a palliative measure for recurrent and/or metastatic (R/M) SCCHN. Recently, immune checkpoint inhibitors have been shown to improve overall survival in R/M-SCCHN and have been incorporated into the standard of care. Combination approaches with immune therapy and targeted therapy for biomarker enriched population based on genomics are being actively investigated and will shape the future of SCCHN treatment.

A genetic association analysis of polymorphisms, rs2282695 and rs12373539, in the FOSB gene and papillary thyroid cancer.

The FOSB gene is involved in cell proliferation, differentiation and transformation in several tumor types. We investigated whether coding single-nucleotide polymorphisms (cSNPs) and promoter SNPs of FOSB contribute to the development of papillary thyroid cancer (PTC). We also assessed the associations between FOSB SNPs and the clinicopathological characteristics of PTC. One coding SNP (rs2282695, Ala39Ala) and one promoter SNP (rs12373539, -158) in the FOSB gene were genotyped using direct sequencing in 94 PTC patients and 213 healthy controls. Genetic data were analyzed using SNPStats, HelixTree and SNPAnalyzer. PTC patients were dichotomized and compared with respect to clinicopathological characteristics of PTC. We detected an association between PTC and cSNP (rs2282695) in FOSB [codominant model 1 (C/C vs. G/C); OR=1.75; 95% CI, 1.04-2.94; P=0.024; codominant model 2 (C/C vs. G/G): OR=2.55; 95% CI, 1.15-5.64; P=0.045; dominant model: OR=1.89; 95% CI, 1.16-3.08; P=0.010; Log-additive model: OR=1.64; 95% CI, 1.15-2.35; P=0.007]. The G allele was a risk allele in the geno-type and allele analyses of cSNP (rs2282695) in the FOSB gene (OR=1.57; 95% CI, 1.10-2.24; P=0.012). A promoter SNP (rs12373539) in FOSB was associated with cervical lymph node metastasis of PTC [codominant model 1 (G/G vs. A/G): OR=0.23; 95% CI, 0.07-0.72; P=0.016; codominant model 2 (G/G vs. A/A): OR=0.21; 95% CI, 0.02-1.96; P=0.0.05; dominant model: OR=0.22; 95% CI, 0.08-0.66; P=0.004; overdominant model: OR=0.27; 95% CI, 0.09-0.84; P=0.02; log-additive model: OR=0.31; 95% CI, 0.12-0.78; P=0.006]. The A allele was a protective allele in the genotype and allele analyses of SNP (rs12373539) in the FOSB gene promoter (OR=0.34; 95% CI, 0.14-0.83; P=0.017). Variation in a FOSB cSNP (rs2282695) may be associated with risk of PTC. The FOSB promoter SNP (rs12373539) may be associated with lymph node metastasis of PTC.