Anti-Allergic Inflammatory Effect of Agarum cribrosum and Its Phlorotannin Component, Trifuhalol A, against the Ovalbumin-Induced Allergic Asthma Model.

Asthma is a chronic inflammatory disease involving structural changes to the respiratory system and severe immune responses mediated by allergic cytokines and pro-inflammatory mediators. Agarum cribrosum (AC) is a kind of seaweed which contains a phlorotannin, trifuhalol A. To evaluate its anti-allergic inflammatory effect against asthma, an ovalbumin inhalation-induced mouse asthma model was used. Histologic observations proved that trifuhalol A is minimizing the lung and tracheal structure changes as well as the infiltration of eosinophils and mast cells against ovalbumin inhalation challenge. From the serum and bronchoalveolar lavage fluid, ovalbumin-specific IgE and Th2-specific cytokines, IL-4, -5, and -13, were reduced with trifuhalol A treatment. In addition, IL-1ß, IL-6, and TNF-α concentrations in lung homogenate were also significantly reduced via trifuhalol A treatment. Taken together, trifuhalol A, isolated from AC, was able to protect lung and airways from Th2-specific cytokine release, and IgE mediated allergic inflammation as well as the attenuation of IL-1ß, IL-6, and TNF-α in lung, which results in the suppression of eosinophils and the mast cells involved asthmatic pathology.

Trifuhalol A Suppresses Allergic Inflammation through Dual Inhibition of TAK1 and MK2 Mediated by IgE and IL-33.

The activation and degranulation of immune cells play a pivotal role in allergic inflammation, a pathological condition that includes anaphylaxis, pruritus, and allergic march-related diseases. In this study, trifuhalol A, a phlorotannin isolated from Agarum cribrosum, inhibited the degranulation of immune cells and the biosynthesis of IL-33 and IgE in differentiated B cells and keratinocytes, respectively. Additionally, trifuhalol A suppressed the IL-33 and IgE-mediated activation of RBL-2H3 cells through the regulation of the TAK1 and MK2 pathways. Hence, the effect of trifuhalol A on allergic inflammation was evaluated using a Compound 48/80-induced systemic anaphylaxis mouse model and a house dust mite (HDM)-induced atopic dermatitis (AD) mouse model. Trifuhalol A alleviated anaphylactic death and pruritus, which appeared as an early-phase reaction to allergic inflammation in the Compound 48/80-induced systemic anaphylaxis model. In addition, trifuhalol A improved symptoms such as itching, edema, erythema, and hyperkeratinization in HDM-induced AD mice as a late-phase reaction. Moreover, the expression of IL-33 and thymic stromal lymphopoietin, inflammatory cytokines secreted from activated keratinocytes, was significantly reduced by trifuhalol A administration, resulting in the reduced infiltration of immune cells into the skin and a reduction in the blood levels of IgE and IL-4. In summarizing the above results, these results confirm that trifuhalol A is a potential therapeutic candidate for the regulation of allergic inflammation.

Trifuhalol A, a phlorotannin from the brown algae Agarum cribrosum, reduces adipogenesis of human primary adipocytes through Wnt/ß-catenin and AMPK-dependent pathways.

Trifuhalol A, a fucol-type phlorotannin, was extracted and identified from the brown algae Agarum cribrosum. The total yield and purity of trifuhalol A from A. cribrosum were 0.98% and 86%, respectively. Trifuhalol A at 22 and 44 µM inhibited lipid accumulation in human primary adipocytes. Consistently trifuhalol A suppressed the expression of adipogenesis-related genes, such as proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein-alpha (C/EBP-α), fatty acid synthase (FAS), and sterol regulatory element-binding protein-1 (SREBP-1), in a dose-dependent manner. Trifuhalol A increased the level of proteins such as wingless/integrated (Wnt)10b, nuclear-ß-catenin, total-ß-catenin, phospho-AMP-activated protein kinase (pAMPK), and phospho-liver kinase B1 (pLKB1) as well as the expression of genes such as Wnt10b, Frizzled 1, and low-density lipoprotein receptor-related protein 6 (LRP6). Additionally, trifuhalol A decreased the expression of the glycogen synthase kinase-3beta (GSK3ß) gene. These results suggest that trifuhalol A reduces fat accumulation in human adipocytes via the Wnt/ß-catenin- and AMPK-dependent pathways.

Antioxidant and antidiabetic activities of vanadium-binding protein and trifuhalol A.

The antioxidant and antidiabetic activities of vanadium-binding protein (VBP) and trifuhalol A, alone or combined, were investigated. Both VBP and trifuhalol A showed potent radical scavenging activity (RSA) on 2,2'-azinobis (3-ethylbenzothiazoline)-6-sulfonic acid (ABTS), hydrogen peroxide, and ferric-reducing antioxidant power. Their combination at a concentration of 100 µg/ml VBP and 40 µg/ml trifuhalol A exhibited more than 99% RSA against ABTS. Additionally, VBP and trifuhalol A, alone or combined, displayed potential antidiabetic activities against Saccharomyces cerevisiae α-glucosidase. The highest inhibition of 70.26% against S. cerevisiae α-glucosidase was observed in the case of the combination of 250 µg/ml VBP and 1.75 µg/ml trifuhalol A. Kinetics study revealed that VBP and trifuhalol A were noncompetitive inhibition type against S. cerevisiae α-glucosidase, while VBP and trifuhalol A combined treatment was a mixed inhibition type against S. cerevisiae α-glucosidase. These results indicated that VBP and trifuhalol A, alone or combined, had high free radical scavenging activity and inhibitory activity against S. cerevisiae a-glucosidase, suggesting that VBP and trifuhalol A could be used as candidates for the development of natural antidiabetic drugs or functional food. PRACTICAL APPLICATIONS: The present study showed that VBP and trifuhalol A, alone or combined, had potential antioxidant and antidiabetic activities, suggesting that VBP and trifuhalol A could be developed to a novel nutraceutical or natural antidiabetic drugs in the management of obesity or diabetes. This finding will be beneficial for all peoples who are directly or indirectly associated with obesity or diabetes.