The Probiotic, ID-JPL934, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice Through Inhibition of Proinflammatory Cytokines Expression.

Despite the increasing prevalence of inflammatory bowel disease (IBD), classified as immune-mediated disorders, the exact biological mechanisms leading to its development are undetermined, and treatment strategies remain elusive. Probiotics have been proposed as potential alternatives for treating IBD. The purpose of this research was to find therapeutic candidates of probiotics for colitis. We adopted dextran sulfate sodium (DSS)-induced colitis model to demonstrate the therapeutic effects of ID-JPL934, a mixture of three live bacterial strains at a 1:1:1 ratio: Lactobacillus johnsonii IDCC9203, Lactobacillus plantarum IDCC3501, and Bifidobacterium animalis subspecies lactis IDCC4301, on IBD. The severity was scored according to the disease activity index (DAI) for colitis by observing body weight (BW) and stool status of each mouse once a day. BALB/c mice given 3.5% DSS in drinking water suffered from symptoms of colitis such as weight loss, diarrhea, and bloody excrement. In our study, administration of ID-JPL934 reduced the DAI scores in a dose-dependent manner, and treatments with ID-JPL934 108 and 109 colony-forming unit per mouse per day showed similar inhibition compared with those of sulfasalazine 500 mg per kg BW per day. Moreover, the contraction of colon length improved. ID-JPL934 also suppressed inflammatory lesions such as infiltration of immune cells in mucosa and submucosa, severe crypt damage, and loss of goblet and epithelial cells on the histological analysis. These results might be due to downregulation of the expression of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. From these results, ID-JPL934 might be an effective therapeutic candidate for IBD.

Chemical Constituents of the Root of Angelica tenuissima and their Anti-allergic Inflammatory Activity.

A phthalide, levistolide A (1), and six coumarins, demethylsuberosin (2), fraxetin (3), (-)-marmesinin (4), 3'(S)-O-P-D-glucopyranosyl-3',4'-dihydroxanthyletin (5), 3'(R)-O-P-D-glucopyranosyl-3',4'-dihydroxanthyletin (6), and isopraeroside IV (7) were isolated from the methanolic extract of the roots of Angelica tenuissima Nakai. Their chemical structures were confirmed by comparing spectroscopic and reported data. All seven compounds were isolated for the first time from this plant source. The anti-allergic activities of compounds 1-7 were examined using human mast cells, and compounds 1-3 at 10 liM potently suppressed IL-6 expression and inhibited histamine release from human mast cells by more than 30%.

Anti-allergic and anti-inflammatory effects of aqueous extract of Pogostemon cablin.

Allergic disease is caused by exposure to normally innocuous substances that activate mast cells. Mast cell-mediated allergic inflammation is closely related to a number of allergic disorders, such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for treating allergic disease is an interesting subject and important to human health. The aim of the present study was to investigate the anti­allergic and anti-inflammatory effects of the aqueous extract of Pogostemon cablin (Blanco) Benth (AEPC) (a member of the Labiatae family) using mast cells, and also to determine its possible mechanisms of action. An intraperitoneal injection of compound 48/80 or a serial injection of immunoglobulin E and antigen was used to induce anaphylaxis in mice. We found that AEPC inhibited compound 48/80­induced systemic and immunoglobulin E-mediated cutaneous anaphylaxis in a dose-dependent manner. The release of histamine from mast cells was reduced by AEPC, and this suppressive effect was associated with the regulation of calcium influx. In addition, AEPC attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated expression of pro-inflammatory cytokines in mast cells. The inhibitory effects of AEPC on pro-inflammatory cytokines were dependent on the activation of nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK). AEPC blocked the PMACI-induced translocation of NF-κB into the nucleus by hindering the degradation of IκBα and the phosphorylation of p38 MAPK. Our results thus indicate that AEPC inhibits mast cell­mediated allergic inflammation by suppressing mast cell degranulation and the expression of pro-inflammatory cytokines caused by reduced intracellular calcium levels and the activation of NF-κB and p38 MAPK.

Inhibitory effect of 1,2,4,5-tetramethoxybenzene on mast cell-mediated allergic inflammation through suppression of IκB kinase complex.

As the importance of allergic disorders such as atopic dermatitis and allergic asthma, research on potential drug candidates becomes more necessary. Mast cells play an important role as initiators of allergic responses through the release of histamine; therefore, they should be the target of pharmaceutical development for the management of allergic inflammation. In our previous study, anti-allergic effect of extracts of Amomum xanthioides was demonstrated. To further investigate improved candidates, 1,2,4,5-tetramethoxybenzene (TMB) was isolated from methanol extracts of A. xanthioides. TMB dose-dependently attenuated the degranulation of mast cells without cytotoxicity by inhibiting calcium influx. TMB decreased the expression of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-4 at both the transcriptional and translational levels. Increased expression of these cytokines was caused by translocation of nuclear factor-κB into the nucleus, and it was hindered by suppressing activation of IκB kinase complex. To confirm the effect of TMB in vivo, the ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and IgE-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA model, hypothermia was decreased by oral administration of TMB, which attenuated serum histamine, OVA-specific IgE, and IL-4 levels. Increased pigmentation of Evans blue was reduced by TMB in a dose-dependent manner in the PCA model. Our results suggest that TMB is a possible therapeutic candidate for allergic inflammatory diseases that acts through the inhibition of mast cell degranulation and expression of pro-inflammatory cytokines.

Anti-allergic inflammatory activities of compounds of amomi fructus.

Activity-guided isolation of compounds from the fruits of Amomum xanthioides resulted in the purification of fourteen phenolic compounds, 4-hydroxy-benzaldehyde (1), 3,4-dihydroxybenzaldehyde (2), 3,5-dimethoxy-4-methylbenzaldehyde (3), syringic aldehyde (4), benzoic acid (5), 3,4-dihydroxy benzoic acid (6), vanillic acid (7), 3-hydroxy-2-methoxybenzoic acid (8), o-vanillic acid (9), phenylacetic acid (10), tyrosol (11), pyrocatechol (12), 1,2,4,5-tetramethoxybenzene (13), and 3,3',5,5'-tetramethoxybiphenyl-4,4'-diol (14). To evaluate the anti-allergic inflammatory activities of these compounds, we examined the inhibitory effects of the isolates (1-14) on histamine release and on the expressions of tumor necrosis factor (TNF)-ca and interleukin (IL)-6 genes by using human mast cells. Of the tested compounds, 9, 11, and 13 suppressed histamine release from mast cells, and all isolates attenuated the expressions of the pro-inflammatory cytokines, TNF-α and IL-6 genes in human mast cells.