Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria.

Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.

Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling.

Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepatocellular carcinoma. Herein, we investigated the pharmacological properties and underlying mechanisms of Gardeniae Fructus (GF) against thioacetamide (TAA)-induced liver fibrosis of mice model. GF not only attenuated hepatic tissue oxidation but also improved hepatic inflammation. We further confirmed that GF led to ameliorating liver fibrosis by ECMs degradations. Regarding the possible underlying mechanism of GF, we observed GF regulated epigenetic regulator, Sirtuin 1 (SIRT1), in TAA-injected liver tissue. These alterations were well supported by SIRT1 related signaling pathways through regulations of its downstream proteins including, AMP-activated protein kinase (AMPK), p47phox, NADPH oxidase 2, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1, respectively. To validate the possible mechanism of GF, we used HepG2 cells with hydrogen peroxide treated oxidative stress and chronic exposure conditions via deteriorations of cellular SIRT1. Moreover, GF remarkably attenuated ECMs accumulations in transforming growth factor-ß1-induced LX-2 cells relying on the SIRT1 existence. Taken together, GF attenuated liver fibrosis through AMPK/SIRT1 pathway as well as Nrf2 signaling cascades. Therefore, GF could be a clinical remedy for liver fibrosis patients in the future.

Characterization of a Novel Fibrinolytic Enzyme, BsfA, from Bacillus subtilis ZA400 in Kimchi Reveals Its Pertinence to Thrombosis Treatment.

Recently, the cardiovascular disease has been widely problematic in humans probably due to fibrin formation via the unbalanced Western style diet. Although direct (human plasmin) and indirect methods (plasminogen activators) have been available, bacterial enzyme methods have been studied because of their cheap and mass production. To detect a novel bacterial fibrinolytic enzyme, 111 bacterial strains with fibrinolytic activity were selected from kimchi. Among them, 14 strains were selected because of their stronger activity than 0.02 U of plasmin. Their 16S rRNA sequence analysis revealed that they belong to Bacillus, Leuconostoc, Propionibacterium, Weissella, Staphylococcus, and Bifidobacterium. The strain B. subtilis ZA400, with the highest fibrinolytic activity, was selected and the gene encoding fibrinolytic enzyme (bsfA) was cloned and expressed in the E. coli overexpression system. The purified enzyme was analyzed with SDS-PAGE, western blot, and MALDI-TOF analyses, showing to be 28.4 kDa. Subsequently, the BsfA was characterized to be stable under various stress conditions such as temperature (4-40°C), metal ions (Mn(2+), Ca(2+), K(2+), and Mg(2+)), and inhibitors (EDTA and SDS), suggesting that BsfA could be a good candidate for development of a novel fibrinolytic enzyme for thrombosis treatment and may even be useful as a new bacterial starter for manufacturing functional fermented foods.

Weissella jogaejeotgali sp. nov., isolated from jogae jeotgal, a traditional Korean fermented seafood.

Strain FOL01T was isolated from traditionally fermented Korean jogae jeotgal (fermented clams). Phylogenetic sequence analysis of the 16S rRNA gene from FOL01T revealed that it is closely related to Weissella thailandensis FS61-1T and Weissella paramesenteroides ATCC 33313T with 99.39 % and 98.50 % 16S rRNA gene sequence similarities, respectively. API and VITEK analyses showed that strain FOL01T could be separated from its nearest phylogenetic relatives with respect to carbohydrate fermentation and antibiotic resistance. Subsequent amplified rRNA gene restriction analysis of 16S rRNA genes and HaeIII-restriction enzyme profiling of genomic DNAs revealed different band patterns. In addition, DNA-DNA hybridization of genomic DNAs showed 63.9 % relatedness. Analysis of the composition of cellular fatty acids confirmed that strain FOL01T differs from its close relatives and supports the proposal to assign this organism to a novel species of the genus Weissella. Based on these results, strain FOL01T could be classified as a novel species of the genus Weissella, for which the name Weissella jogaejeotgali sp. nov. is proposed. The type strain is FOL01T ( = KCCM 43128T = JCM 30589T).