RESUMEN
(-)-Epigallocatechin-3-O-(3-O-methyl) gallate (1, EGCG3â³Me), an antiallergic O-methylated catechin, is present in high quantities in the green tea cultivar "Benifuuki" (Camellia sinensis L.). Previous studies have shown that EGCG3â³Me inhibited basophil degranulation mediated through the cell-surface 67-kDa laminin receptor (67LR), but the mechanisms are not fully elucidated. This study aimed to investigate the mechanisms underlying the inhibitory effect of EGCG3â³Me on IgE/antigen (Ag)-mediated degranulation and the combined effect of EGCG3â³Me with eriodictyol (2), a bioactive flavanone. EGCG3â³Me inhibited ß-hexosaminidase release from the rat basophilic/mast cell line RBL-2H3 stimulated by IgE/Ag and induced acid sphingomyelinase (ASM) activity. This induction was inhibited by anti-67LR antibody treatment. The ASM-specific inhibitor desipramine inhibited EGCG3â³Me-induced suppression of degranulation. The soluble guanylate cyclase (sGC) inhibitor NS2028 weakened the potency of EGCG3â³Me, and the sGC activator BAY41-2272 suppressed degranulation. The ability of EGCG3â³Me to induce ASM activity and inhibit degranulation was amplified by eriodictyol. Furthermore, oral administration of the lemon-peel-derived eriodyctiol-7-O-glucoside (3) potentiated the suppressive effect of EGCG3â³Me-rich "Benifuuki" green tea on the IgE/Ag-induced passive cutaneous anaphylaxis (PCA) reaction in BALB/c mice. These results suggest that EGCG3â³Me inhibits IgE/Ag-mediated degranulation by inducing the 67LR/sGC/ASM signaling pathway, and eriodictyol amplifies this signaling.
Asunto(s)
Antialérgicos/farmacología , Catequina/farmacología , Flavanonas/farmacología , Receptores de Laminina/metabolismo , Animales , Camellia sinensis/química , Línea Celular , Femenino , Mastocitos/efectos de los fármacos , Ratones Endogámicos BALB C , Ratas , Transducción de Señal/efectos de los fármacos , TéRESUMEN
Many patients with allergies have anxiety about taking anti-allergic medicines due to their side effects and increased medical expenses. Thus, developing functional foods/agricultural products for allergy prevention is strongly desired. In this study, we revealed that a Citrus flavanone, hesperetin, amplified IgE/antigen-mediated degranulation-inhibitory potency of anti-allergic catechin, (-)-epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3''Me), in the rat basophilic/mast cell line RBL-2H3. Hesperetin also significantly elevated the activation of acid sphingomyelinase (ASM), essential for eliciting anti-allergic effect of EGCG3''Me through the cell surficial protein, 67-kDa laminin receptor (67LR). Furthermore, oral administration of the highly absorbent hesperidin, α-glucosyl hesperidin, also enhanced the inhibitory potency of EGCG3''Me-rich 'Benifuuki' green tea (Camellia sinensis L.) on passive cutaneous anaphylaxis (PCA) reaction evoked by IgE/antigen in BALB/c mice. These observations indicate that hesperetin amplifies the ability of EGCG3''Me to inhibit the IgE/antigen-mediated degranulation through activating ASM signaling.
Asunto(s)
Antialérgicos , Catequina , Flavanonas , Hesperidina , Ratas , Ratones , Animales , Antialérgicos/farmacología , Inmunoglobulina E , Anafilaxis Cutánea PasivaRESUMEN
(-)-epigallocatechin-3-O-gallate (EGCG) is a bioactive polyphenol in green tea. Previous studies have demonstrated the beneficial effects of EGCG on muscle mass and muscle atrophy. In the current study, we investigated the mechanisms underlying effect of EGCG on muscle atrophy. It was demonstrated that EGCG suppressed muscle-specific ubiquitin ligase, muscle RING Finger 1 (MuRF1) expression through 67-kDa laminin receptor (67LR). Previous studies have shown that eriodictyol potentiates the anti-tumor activities of EGCG by amplifying 67LR signaling. Therefore, we investigated the effects of EGCG and eriodictyol on the MuRF1 expression in C2C12 myotubes. The combined treatment of EGCG and eriodictyol significantly suppressed MuRF1 expression in dexamethasone-treated C2C12 myotubes. Tail suspension was maintained for 10 consecutive days using C57BL6/J mice, and during this time EGCG and eriodictyol were orally administered. In the gastrocnemius muscle, the muscle mass loss was inhibited by the combination of EGCG and eriodictyol. Therefore, EGCG may prevent muscle atrophy by inducing 67LR signaling and eriodictyol amplifies this pathway.
Asunto(s)
Catequina/análogos & derivados , Flavanonas/metabolismo , Proteínas Musculares/metabolismo , Plantas/química , Receptores de Laminina/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Catequina/química , Regulación hacia Abajo , Ratones , Transducción de SeñalRESUMEN
Green tea and its major polyphenol epigallocatechin-3-O-gallate (EGCG) have suppressive effect on dietary obesity. However, it remains unsolved what type of diet on which they exhibit high or low anti-obesity effect. In the present study, we investigated whether anti-obesity effect of green tea differs depending on composition of fats or fatty acids that consist high-fat (HF) diet in mouse model. Green tea extract (GTE) intake dramatically suppressed weight gain and fat accumulation induced by olive oil-based HF diet, whereas the effects on those induced by beef tallow-based HF diet were weak. GTE also effectively suppressed obesity induced by unsaturated fatty acid-enriched HF diet with the stronger effect compared with that induced by saturated fatty acid-enriched HF diet. These differences would be associated with the increasing action of GTE on expression of PPARδ signaling pathway-related genes in the white adipose tissue. Expressions of genes relating to EGCG signaling pathway that is critical for exhibition of physiological effects of EGCG were also associated with the different effects of GTE. Here, we show that anti-obesity effect of GTE differs depending on types of fats or fatty acids that consist HF diet and could be attenuated by saturated fatty acid.