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Eisenia arborea, an edible brown alga, is occasionally used as a folk medicine due to its anti-allergic e#ect. In the present study to identify the anti-allergic constituents in the alga, the extract of the alga was purified by partition between solvents and by reversed phase chromatography. Separation of the extract was guided by the inhibitory activity upon b-hexosaminidase release from the rat basophilic leukemia-,Hcells. HPLC purification a#orded six active compounds. Spectral analyses clarified their structures as eckol, 0,0῎-bieckol, 0,2῎-bieckol, 2,2῎-bieckol, phlorofucofuroeckol-A, and phlorofucofuroeckol-B. Most of the phlorotannins exhibited activities similar to or greater than the typical inhibitor, epigallocatechin gallate. Phlorofucofuroeckol-B showed the greatest activity among the tested phlorotannins at ,.2 times greater than epigallocatechin gallate.

Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks. BCAA supplementation significantly improved hepatic steatosis, inflammation, fibrosis, and tumors in Ath+HF mice at 68 weeks. GeneChip analysis demonstrated the significant resolution of pro-fibrotic gene expression by BCAA supplementation. The anti-fibrotic effect of BCAA was confirmed further using platelet-derived growth factor C transgenic mice, which develop hepatic fibrosis and tumors. In vitro, BCAA restored the transforming growth factor (TGF)-β1-stimulated expression of pro-fibrotic genes in hepatic stellate cells (HSC). In hepatocytes, BCAA restored TGF-β1-induced apoptosis, lipogenesis, and Wnt/β-Catenin signaling, and inhibited the transformation of WB-F344 rat liver epithelial stem-like cells. BCAA repressed the promoter activity of TGFβ1R1 by inhibiting the expression of the transcription factor NFY and histone acetyltransferase p300. Interestingly, the inhibitory effect of BCAA on TGF-β1 signaling was mTORC1 activity-dependent, suggesting the presence of negative feedback regulation from mTORC1 to TGF-β1 signaling. Thus, BCAA induce an anti-fibrotic effect in HSC, prevent apoptosis in hepatocytes, and decrease the incidence of HCC; therefore, BCAA supplementation would be beneficial for patients with advanced liver fibrosis with a high risk of HCC.

We used human peripheral lung from 8 mildly asthmatic patients and 11 normal donors to study the expression of muscarinic and beta-adrenergic receptors in asthma. There was no significant difference in the affinity or the density of muscarinic (labeled with [N-methyl-3H]scopolamine) and beta 1- and beta 2-adrenergic receptors (labeled with [125I]iodocyanopindolol) in peripheral lung from asthmatics compared with nonasthmatics. Only the muscarinic m1 receptor mRNA was detected in human lung using Northern blot analysis. Additionally, peripheral lung cellular mRNA hybridized to human beta 1 and beta 2 cDNA probes, giving 3.2- and 2.2-kb hands corresponding to beta 1 and beta 2-adrenergic receptors mRNA, respectively. Densitometric scanning of the autoradiograms suggests that there was no significant difference in the relative abundance of muscarinic m1 and beta 1- and beta 2-adrenergic receptor mRNA in asthmatic compared with nonasthmatic lungs. Functional experiments obtained in trachea suggest that there was an increase in the cholinergic neural response evoked by electrical field stimulation in asthmatic compared with nonasthmatic tissues which was not due to a reduction in inhibitory noncholinergic nonadrenergic relaxations.

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