<i>Salvia miltiorrhiza</i> Root Extract as a Potential Therapeutic Agent for IgE/Ag-Induced Allergic Reactions and Atopic Dermatitis via the Syk/MAPK Pathway

<b>Background/Objectives</b>: Allergens can trigger severe immune responses in hypersensitive individuals, with mast cells releasing inflammatory mediators via IgE-FcɛRI signaling. Spleen tyrosine kinase (Syk) is a key regulator in this pathway, making it a promising therapeutic target....

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Main Authors: Min-ah Kim, Jin-Ho Lee, Keunjung Woo, Eunwoo Jeong, Tack-Joong Kim
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/7/1547
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author Min-ah Kim
Jin-Ho Lee
Keunjung Woo
Eunwoo Jeong
Tack-Joong Kim
author_facet Min-ah Kim
Jin-Ho Lee
Keunjung Woo
Eunwoo Jeong
Tack-Joong Kim
author_sort Min-ah Kim
collection DOAJ
description <b>Background/Objectives</b>: Allergens can trigger severe immune responses in hypersensitive individuals, with mast cells releasing inflammatory mediators via IgE-FcɛRI signaling. Spleen tyrosine kinase (Syk) is a key regulator in this pathway, making it a promising therapeutic target. Natural modulators of Syk-mediated mast cell activation remain underexplored. This study investigated the anti-allergic effects of a 70% ethanol extract of <i>Salvia miltiorrhiza</i> (SME) using in vitro and in vivo models. <b>Methods</b>: SME was evaluated using IgE-sensitized RBL-2H3 cells, a passive cutaneous anaphylaxis model, and a DNCB-induced atopic dermatitis-like mouse model. Allergic responses were assessed via degranulation assays, histopathology, serum IgE levels, and the spleen index. <b>Results</b>: SME significantly inhibited mast cell degranulation by 44.4 ± 1.6% in RBL-2H3 cells at 100 µg/mL following 30 min of treatment compared to the untreated control. Western blot analysis demonstrated dose-dependent suppression of protein kinase B (PKB, also known as AKT), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and spleen tyrosine kinase (Syk) phosphorylation, indicating inhibition of key allergic signaling pathways. In an IgE/Ag-induced passive cutaneous anaphylaxis model in ICR mice, SME (100 mg/kg, orally) significantly attenuated vascular permeability, as evidenced by a 20.6 ± 9.7% reduction in Evans blue extravasation relative to the Ag-treated group. In a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD)-like model, six treatments of SME significantly improved the skin condition, reduced spleen enlargement associated with allergic inflammation, and decreased serum IgE levels by 43.3 ± 11.2% compared to the DNCB group. <b>Conclusions</b>: These findings suggest that SME may help to alleviate allergic responses and AD by modulating key immune signaling pathways.
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spelling doaj-art-79cd93498db64d04a64a8d98b271f4952025-08-20T03:36:02ZengMDPI AGBiomedicines2227-90592025-06-01137154710.3390/biomedicines13071547<i>Salvia miltiorrhiza</i> Root Extract as a Potential Therapeutic Agent for IgE/Ag-Induced Allergic Reactions and Atopic Dermatitis via the Syk/MAPK PathwayMin-ah Kim0Jin-Ho Lee1Keunjung Woo2Eunwoo Jeong3Tack-Joong Kim4Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea<b>Background/Objectives</b>: Allergens can trigger severe immune responses in hypersensitive individuals, with mast cells releasing inflammatory mediators via IgE-FcɛRI signaling. Spleen tyrosine kinase (Syk) is a key regulator in this pathway, making it a promising therapeutic target. Natural modulators of Syk-mediated mast cell activation remain underexplored. This study investigated the anti-allergic effects of a 70% ethanol extract of <i>Salvia miltiorrhiza</i> (SME) using in vitro and in vivo models. <b>Methods</b>: SME was evaluated using IgE-sensitized RBL-2H3 cells, a passive cutaneous anaphylaxis model, and a DNCB-induced atopic dermatitis-like mouse model. Allergic responses were assessed via degranulation assays, histopathology, serum IgE levels, and the spleen index. <b>Results</b>: SME significantly inhibited mast cell degranulation by 44.4 ± 1.6% in RBL-2H3 cells at 100 µg/mL following 30 min of treatment compared to the untreated control. Western blot analysis demonstrated dose-dependent suppression of protein kinase B (PKB, also known as AKT), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and spleen tyrosine kinase (Syk) phosphorylation, indicating inhibition of key allergic signaling pathways. In an IgE/Ag-induced passive cutaneous anaphylaxis model in ICR mice, SME (100 mg/kg, orally) significantly attenuated vascular permeability, as evidenced by a 20.6 ± 9.7% reduction in Evans blue extravasation relative to the Ag-treated group. In a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD)-like model, six treatments of SME significantly improved the skin condition, reduced spleen enlargement associated with allergic inflammation, and decreased serum IgE levels by 43.3 ± 11.2% compared to the DNCB group. <b>Conclusions</b>: These findings suggest that SME may help to alleviate allergic responses and AD by modulating key immune signaling pathways.https://www.mdpi.com/2227-9059/13/7/1547<i>Salvia miltiorrhiza</i>allergyanaphylaxisatopic dermatitis
spellingShingle Min-ah Kim
Jin-Ho Lee
Keunjung Woo
Eunwoo Jeong
Tack-Joong Kim
<i>Salvia miltiorrhiza</i> Root Extract as a Potential Therapeutic Agent for IgE/Ag-Induced Allergic Reactions and Atopic Dermatitis via the Syk/MAPK Pathway
Biomedicines
<i>Salvia miltiorrhiza</i>
allergy
anaphylaxis
atopic dermatitis
title <i>Salvia miltiorrhiza</i> Root Extract as a Potential Therapeutic Agent for IgE/Ag-Induced Allergic Reactions and Atopic Dermatitis via the Syk/MAPK Pathway
title_full <i>Salvia miltiorrhiza</i> Root Extract as a Potential Therapeutic Agent for IgE/Ag-Induced Allergic Reactions and Atopic Dermatitis via the Syk/MAPK Pathway
title_fullStr <i>Salvia miltiorrhiza</i> Root Extract as a Potential Therapeutic Agent for IgE/Ag-Induced Allergic Reactions and Atopic Dermatitis via the Syk/MAPK Pathway
title_full_unstemmed <i>Salvia miltiorrhiza</i> Root Extract as a Potential Therapeutic Agent for IgE/Ag-Induced Allergic Reactions and Atopic Dermatitis via the Syk/MAPK Pathway
title_short <i>Salvia miltiorrhiza</i> Root Extract as a Potential Therapeutic Agent for IgE/Ag-Induced Allergic Reactions and Atopic Dermatitis via the Syk/MAPK Pathway
title_sort i salvia miltiorrhiza i root extract as a potential therapeutic agent for ige ag induced allergic reactions and atopic dermatitis via the syk mapk pathway
topic <i>Salvia miltiorrhiza</i>
allergy
anaphylaxis
atopic dermatitis
url https://www.mdpi.com/2227-9059/13/7/1547
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