Anti-allergic effects of Rosae multiflorae fructus via inhibition of T cell proliferation and the mast cell function

누엔티민누엣,Maria Lomunova,신희순,손동화,김영호,황인규 한국응용생명화학회 2017 Applied Biological Chemistry (Appl Biol Chem) Vol.60 No.4

Anti-allergic effects of the hot water extract of Rosae multiflorae fructus (Rosae extract), which has long been used in oriental medicine for treatment of various diseases, were explored with a chicken ovalbumin (cOVA)-induced mouse model of food allergy. Compared to the sham mice to show severe allergic symptoms (i.e., anaphylaxis, diarrhea and decrease in the body temperature) following oral cOVA challenge, the Rosae extracttreated mice showed a marked improvement in those symptoms. Histology data demonstrated that Rosae extract treatment resulted in a amelioration in the intestinal inflammatory lesion and a reduction in the numbers of mast cells and eosinophils in the small intestine. Studies using DO11.10 TCR transgenic T cells indicated that Rosae extract had an activity to subdue the antigen-specific T cell activation/proliferation in vivo and thereby to lower the level of Th2 cytokine production by T cells during the antigen-specific immune response. Moreover, passive systemic anaphylaxis study showed that the extract also had an activity to inhibit the mast cells function in vivo, i.e., release of granules triggered by specific IgE-antigen interaction. Altogether, the results from this study not only imply a potential clinical application of Rosae extract in prevention and treatment of food allergy but also clearly elucidate the immunoregulatory mechanisms of Rosae extract underlying its anti-allergic effect.

Anti-allergic effects of the ethanol extract of <i>Syzygium formosum</i> (Wall.) Masam leaves and its immunoregulatory mechanisms

Nguyen, Thi Minh Nguyet,Lomunova, Maria,Vu, Thi Phuong Duyen,Le, Ba Vinh,Kim, Young Ho,Kang, Jong Seong,Hwang, Inkyu Elsevier 2018 Journal of Ethnopharmacology Vol.211 No.-

<P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P>As documented in a Vietnamese traditional medical encyclopedia, <I>Syzygium formosum</I> (Wall.) Masam leaves have been routinely used among indigenous Vietnamese people for treatment of various allergy-like symptoms including dermatitis and rhinitis.</P> <P><B>Aim of the study</B></P> <P>Anti-allergic activity of <I>S. formosum</I> leaves was examined with a mouse model of chicken ovalbumin (cOVA)-induced food allergy, and mechanisms underlying the anti-allergic effect were explored.</P> <P><B>Material and methods</B></P> <P>BALB/c mice were administered i.p. cOVA (20μg) plus alum (2mg) twice on day 0 and 14 for sensitization (immunization). Two weeks after the second immunization, the mice were administered cOVA (50mg) p.o. 5 times every 3 days to induce food allergy symptoms (i.e., anaphylaxis, diarrhea, and drop in the body temperature). Ethanol extract of dried leaves of <I>S. formosum</I> (80mg/kg or 200mg/kg body weight) was administered p.o. daily during the induction (challenge) period.</P> <P><B>Results</B></P> <P>Treatment with the <I>S. formosum</I> leaves ethanol extract ameliorated the allergic symptoms to a significant extent and in a dose-dependent manner. The treatment also resulted in a significant improvement in the inflammatory lesion in the small intestine and reduction in the numbers of mast cells and eosinophils recruited to the lesion. The treatment also brought about a significant reduction in the levels of Th2 cytokines produced by the mesenteric lymph node cells cultured ex vivo with cOVA. The passive anaphylaxis experiment also showed that the extract treatment impaired the mast cell function.</P> <P><B>Conclusion</B></P> <P>Our study provides a scientific basis for the traditional (indigenous) use of the <I>S. formosum</I> leaves extract for the treatment of various allergy symptoms in Vietnam. In addition, the results show that the extract has activities to suppress antigen-specific Th2 T cell immune responses and the mast cell function, which are directly related with its anti-allergic effect.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

The mast cell stabilizing activity of Chaga mushroom critical for its therapeutic effect on food allergy is derived from inotodiol

Nguyet, Thi Minh Nguyen,Lomunova, Maria,Le, Ba Vinh,Lee, Ji Sun,Park, Seol Kyu,Kang, Jong Seong,Kim, Young Ho,Hwang, Inkyu Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.54 No.-

<P><B>Abstract</B></P> <P>While an anti-allergic effect of Chaga mushroom (<I>Inonotus obliquus</I>) has been indicated, its therapeutic effect on allergy and immunoregulatory mechanisms and chemical constituents directly responsible for that are hardly known. We examined the effect of 70% ethanol extract of Chaga mushroom (EE) and its dichloromethane (DF) and aqueous (AF) fractions using a mouse model of chicken ovalbumin (cOVA)-induced food allergy, and found that only EE and DF ameliorated allergy symptoms to a significant extent. The in vivo mast cell-stabilizing activity was also found only in EE and DF whereas the activities to suppress Th2 and Th17 immune responses and cOVA-specific IgE production in the small intestine were observed in all three treatment regimens, implying that inhibition of the mast cell function by lipophilic compounds was vital for the therapeutic effect. Results also indicated that inotodiol, a triterpenoid predominantly present in DF, played an active role as a mast cell stabilizer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 70% EtOH extract of Chaga mushroom has a good therapeutic effect on food allergy. </LI> <LI> A Mast cell stabilizing activity is key for the effect of Chaga mushroom. </LI> <LI> Only CH<SUB>2</SUB>Cl<SUB>2</SUB> fraction, but not H<SUB>2</SUB>O fraction, has the mast cell stabilizing activity. </LI> <LI> Inotodiol, a tetracyclic triterpenoid, is predominantly present in CH<SUB>2</SUB>Cl<SUB>2</SUB> fraction. </LI> <LI> Inotodiol holds a strong mast cell stabilizing activity. </LI> </UL> </P>

Potentiation of T Cell Stimulatory Activity by Chemical Fixation of a Weak Peptide-MHC Complex

황인규,김광미,최소진,Maria Lomunova 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.1

The stability of peptide-MHC complex (pMHC) is an important factor to shape the fate of peptide-specific T cell immune response, but how it influences on T cell activation process is poorly understood. To better understand that, we investigated various T cell activation events driven by Ld MHCI loaded with graded concentrations of P2Ca and QL9 peptides, respectively, with 2C TCR Tg T cells; the binding strength of P2Ca for Ld is measurably weaker than that of QL9, but either peptides in the context of Ld interact with 2C TCR with a similar strength. When their concentrations required for early T cell activation events, which occur within several minutes to an hour, were concerned, EC50s of QL9 were about 100 folds lower than those of P2Ca, which was expected from their association constants for Ld. When EC50s for late activation events, which takes over several hours to occur, were concerned, the differences grew even larger (> 300 folds), suggesting that, due to weak binding, Ld/P2Ca dissociate from each other more easily to lose its antigenicity in a short time. Accordingly, fixation of Ld/P2Ca with paraformaldehyde resulted in a significant improvement in its immunogenicity. These results imply that binding strength of a peptide for a MHC is a critical factor to determine the duration of pMHC-mediated T cell activation and thus the attainment of productive T cell activation. It is also suggested that paraformaldehyde fixation should be an effective tool to ameliorate the immunogenicity of pMHC with a poor stability.

Potentiation of T Cell Stimulatory Activity by Chemical Fixation of a Weak Peptide-MHC Complex

Hwang, Inkyu,Kim, Kwangmi,Choi, Sojin,Lomunova, Maria Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.1

The stability of peptide-MHC complex (pMHC) is an important factor to shape the fate of peptide-specific T cell immune response, but how it influences on T cell activation process is poorly understood. To better understand that, we investigated various T cell activation events driven by $L^d$ MHCI loaded with graded concentrations of P2Ca and QL9 peptides, respectively, with 2C TCR Tg T cells; the binding strength of P2Ca for $L^d$ is measurably weaker than that of QL9, but either peptides in the context of $L^d$ interact with 2C TCR with a similar strength. When their concentrations required for early T cell activation events, which occur within several minutes to an hour, were concerned, $EC_{50}s$ of QL9 were about 100 folds lower than those of P2Ca, which was expected from their association constants for $L^d$. When $EC_{50}s$ for late activation events, which takes over several hours to occur, were concerned, the differences grew even larger (> 300 folds), suggesting that, due to weak binding, $L^d/P2Ca$ dissociate from each other more easily to lose its antigenicity in a short time. Accordingly, fixation of $L^d/P2Ca$ with paraformaldehyde resulted in a significant improvement in its immunogenicity. These results imply that binding strength of a peptide for a MHC is a critical factor to determine the duration of pMHC-mediated T cell activation and thus the attainment of productive T cell activation. It is also suggested that paraformaldehyde fixation should be an effective tool to ameliorate the immunogenicity of pMHC with a poor stability.