Sphingoid base in pineapple glucosylceramide suppresses experimental allergy by binding leukocyte mono-immunoglobulin-like receptor 3.

BACKGROUND: The increase in patients suffering from type I hypersensitivity, including hay fever and food allergy, is a serious public health issue around the world. Recent studies have focused on allergy prevention by food factors with fewer side effects. The purpose of this study was to evaluate the effect of dietary glucosylceramide from pineapples (P-GlcCer) on type I hypersensitivity and elucidate mechanisms. RESULTS: Oral administration of P-GlcCer inhibited ear edema in passive cutaneous anaphylaxis reaction. In a Caco-2/RBL-2H3 co-culture system, P-GlcCer inhibited ß-hexosaminidase release from RBL-2H3 cells. The direct treatment of P-GlcCer on RBL-2H3 did not affect ß-hexosaminidase release, but sphingoid base moiety of P-GlcCer did. These results predicted that sphingoid base, a metabolite of P-GlcCer, through the intestine inhibited type I hypersensitivity by inhibiting mast cell degranulation. In addition, the inhibitory effects of P-GlcCer on ear edema and degranulation of RBL-2H3 cells were canceled by pretreatment of leukocyte mono-immunoglobulin-like receptor 3 (LMIR3)-Fc, which can block LMIR3-mediated inhibitory signals. CONCLUSION: It was demonstrated that a sphingoid base, one of the metabolites of P-GlcCer, may inhibit mast cell degranulation by binding to LMIR3. The oral administration of P-GlcCer is a novel and attractive food factor that acts directly on mast cells to suppress allergy. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Lactiplantibacillus plantarum 22A-3-induced TGF-ß1 secretion from intestinal epithelial cells stimulated CD103+ DC and Foxp3+ Treg differentiation and amelioration of colitis in mice.

In the present study, we evaluated the anti-inflammatory properties of Lactiplantibacillus plantarum 22A-3 (LP22A3) and attempted to elucidate the underlying molecular mechanism. The oral administration of LP22A3 significantly inhibited body weight reduction and decreased colon shortening and colitis score in mice with dextran sulfate sodium (DSS)-induced colitis. It was demonstrated that the production of the active-form of TGF-ß tended to increase in both the intestinal epithelial cells (IECs) of the ileum and serum but not in the colon of non-DSS-treated mice by LP22A3. IL-10 level in serum was also elevated by LP22A3-treatment. The mRNA expression of TGF-ß, IL-10 and Foxp3 increased only in the small intestines of LP22A3-treated mice. Both the aldehyde dehydrogenase 1 family member A2 (Aldh1a2) mRNA expression and population of CD103+ dendritic cells (DCs) in the small intestine significantly increased in the LP22A3-treated group. LP22A3 induced TGF-ß secretion from the IECs of the small intestine with retinoic acid production probably through TLR2, resulting in an increase in CD103+ DCs and the Foxp3+ Treg population. Both cells secrete a high level of anti-inflammatory cytokines, TGF-ß and IL-10 contributing to the protective condition in the intestine and thus making it less susceptible to inflammation. This suggested that oral administration of LP22A-3 may be an alternative therapeutic strategy for IBD.

Lactiplantibacillus plantarum 22A-3 isolated from pickle suppresses ovalbumin-induced food allergy in BALB/c mice and 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice.

In the previous study, pickle-derived Lactiplantibacillus plantarum 22A-3 (LP22A3) suppressed ear edema in passive cutaneous anaphylaxis by its oral administration. Moreover, LP22A3 treatment directly to RBL-2H3 cells shows no effect on ß-hexosaminidase release from RBL-2H3 but inhibited its release using the Caco-2/RBL-2H3 cells co-culture system stimulated with LP22A3 from the apical side. In this study, oral administration of LP22A3 decreased total IgE and ovalbumin (OVA) specific IgE contents in blood of BALB/c mice induced food allergy by OVA. Moreover, its oral administration suppressed the development of dermatitis induced by 2,4-dinitrochlorobenzene (DNCB) which was used to develop atopic dermatitis-like lesions in NC/Nga mice. This alleviation was further correlated with a reduction of elevated serum total IgE, transepidermal water loss and elevated acanthosis in the LP22A3-treated group compared with vehicle-treated positive group. In co-culture system composed of Caco-2 and RBL-2H3 cells, LP22A3 treatment on apical side before or after the sensitization with anti-dinitrophenyl (DNP) IgE antibody indicated the different effect on ß-hexosaminidase release from RBL-2H3. Its treatment before the sensitization decreased ß-hexosaminidase release, but not after sensitization, indicating that LP22A3 affected mast cells sensitized with allergen through intestinal epithelial cells. These results suggest that LP22A3 may have a potential therapeutic property for Type 1 hypersensitivity and atopic dermatitis.

Lactobacillus plantarum 22A-3 exerts anti-allergic activity through TGF-ß secretion in passive cutaneous anaphylaxis of mice.

Allergy is a global issue, however, medical intervention for allergy treatment is limited. Recent studies have focussed on allergy prevention with food factors. In this study, Lactobacillus plantarum 22 A-3 (LP22A3) exerted an anti-allergic effect in passive cutaneous anaphylaxis (PCA) reaction and increased transforming growth factor (TGF)-ß contents in blood. The increase of TGF-ß contents in blood by exogenous TGF-ß injection intraperitoneally decreased Evans blue release into mice ears to the same level as LP22A3 treatment in PCA reaction. LP22A3 treatment directly to RBL-2H3 cells shows no effect on ß-hexosaminidase release from RBL-2H3 but inhibited its release using the Caco-2/RBL-2H3 cells co-culture system stimulated with LP22A3 from the apical side. Moreover, TGF-ß treatment to RBL-2H3 inhibited ß-hexosaminidase release from RBL-2H3. However, ß-hexosaminidase release was cancelled by TGF-ß neutralising antibody without the influence of TGF-ß mRNA expression in Caco-2 cells. These results showed that LP22A3 ameliorates allergy by TGF-ß secretion through the intestine.

Toxicological evaluation of standardized Kaempferia parviflora extract: Sub-chronic and mutagenicity studies.

Kaempferia parviflora (KP), also known as Krachai-dam in Thailand, belongs to the family Zingiberaceae and has been used traditionally to improve blood flow and treat inflammatory, allergic, and gastrointestinal disorders. The objective of this study was to investigate the safety profile of a standardized hydroalcoholic KP rhizome extract via mutagenicity and sub-chronic toxicity evaluations using in vitro and in vivo techniques. The in vitro mutagenicity of KP extract was assessed via reverse mutation tests using Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and Escherichia coli WP2 uvrA. The sub-chronic toxicity profile was evaluated after daily oral administration of KP extract to Sprague-Dawley rats for 90 days. General toxicological parameters were monitored weekly. After the treatment period, blood was collected for hematological and biochemical analyses and certain organs were removed for macroscopic and histopathological analyses. Reverse mutation tests revealed that KP extract did not induce gene mutations at any of the concentrations tested. In the sub-chronic toxicity test, a few changes were observed, including increased salivation in the animals administered high-dose KP extract (249 mg/kg body weight (bw)/day). No toxicologically relevant changes were observed in the biochemical analysis. Sub-chronic administration of KP extract increased platelet levels in animals administered low-dose KP extract (25 mg/kg bw/day). However, the hematological and biochemical parameters remained within normal physiological ranges for the animal species. No toxicological changes were observed in the macroscopic and histopathological analyses performed in this study. These results demonstrate that KP extract is not genotoxic and that 90-day oral administration of the doses tested did not result in toxicity. Therefore, KP extract has a high safety margin for daily use.

Kohki tea protects the rabbit bladder from ischemia/reperfusion-induced contractile dysfunction.

OBJECTIVES: Results of several studies indicated that ischemia/reperfusion is an etiological factor in obstructive bladder dysfunction. Kohki tea pretreatment was shown to reduce the dysfunctions induced by partial outlet obstruction in rabbits. The current study was designed to determine if pretreatment of rabbits with Kohki tea could prevent the contractile dysfunctions induced by bilateral ischemia followed by reperfusion. METHODS: New Zealand white rabbits were separated into several groups; one half of each group was pretreated by oral gavage for 3 weeks with Kohki tea and the other half was treated with vehicle (water). Experimental groups were subjected to bilateral ischemia for either 1 or 3 h followed by reperfusion for either 1 h or 1 week (4 groups). The results from the experimental groups were compared to the groups of rabbits receiving sham operations. RESULTS: Under all experimental conditions, Kohki tea significantly reduced the contractile dysfunctions induced by ischemia and ischemia followed by reperfusion. CONCLUSIONS: This data is consistent with the concept that Kohki tea acts by protecting the bladder smooth muscle and mucosa from cellular damage caused by ischemia/reperfusion.