scholarly journals Immunosuppressive effect of hispidulin in allergic contact dermatitis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Premrutai Thitilertdecha ◽  
Panwadee Pluangnooch ◽  
Sunita Timalsena ◽  
Kitipong Soontrapa

Abstract Background Long-term use of most immunosuppressants to treat allergic contact dermatitis (ACD) generates unavoidable severe side effects, warranting discovery or development of new immunosuppressants with good efficacy and low toxicity is urgently needed to treat this condition. Hispidulin, a flavonoid compound that can be delivered topically due to its favorable skin penetrability properties, has recently been reported to possess anti-inflammatory and immunosuppressive properties. However, no studies have investigated the effect of hispidulin on Th1 cell activities in an ACD setting. Methods A contact hypersensitivity (CHS) mouse model was designed to simulate human ACD. The immunosuppressive effect of hispidulin was investigated via ear thickness, histologic changes (i.e., edema and spongiosis), and interferon-gamma (IFN-γ) gene expression in 1-fluoro-2,4-dinitrobenzene (DNFB)-sensitized mice. Cytotoxicity, total number of CD4+ T cells, and percentage of IFN-γ-producing CD4+ T cells were also investigated in vitro using isolated CD4+ T cells from murine spleens. Results Topically applied hispidulin effectively inhibited ear swelling (as measured by reduction in ear thickness), and reduced spongiosis, IFN-γ gene expression, and the number of infiltrated immune cells. The inhibitory effect of hispidulin was observed within 6 h after the challenge, and the observed effects were similar to those effectuated after dexamethasone administration. Hispidulin at a concentration up to 50 μM also suppressed IFN-γ-producing CD4+ T cells in a dose-dependent manner without inducing cell death, and without a change in total frequencies of CD4+ T cells among different concentration groups. Conclusion The results of this study, therefore, suggest hispidulin as a novel compound for the treatment of ACD via the suppression of IFN-γ production in Th1 cells.

Author(s):  
Martin Raemond Brondial Mallabo ◽  
Mary Jho - Anne T. Corpuz ◽  
Reginald B. Salonga ◽  
Ross D. Vasquez

Purpose: Sulfated polysaccharide (SP) from Codium species has been reported for its anti-inflammatory activities. However, the effect of SP from C. edule on allergic responses has not been studied. The study was conducted to determine the effect of SP (F1) from C. edule on allergic contact dermatitis (ACD) induced by 2,4-dinitrofluorobenzene (DNFB) in female BALB/c mice. Methods: F1 was isolated using DEAE Sepharose Gel Chromatography and chemically identified by LC-MS analyses. The effects of F1 on changes in ear thickness, allergic responses, and histology were evaluated. The effects of F1 on the production of inflammatory cytokines IFN- γ and TNF-α in serum were also quantified and compared with standard prednisolone therapy. Results: F1 was identified as a heteropolysaccharide with β-D-galactans and β-L-arabinans units. F1 was non-toxic at 2000 mg/kg. Administration of F1 in DNFB-challenged mice significantly suppressed the increase in ear thickness, erythema, desquamation, and proliferation of inflammatory cells. F1 significantly decreased the production of inflammatory markers, IFN- γ and TNF-α in a dose-dependent manner when compared to the untreated group (p<0.05). Conclusion: Results suggest that F1 from C. edule is a bioactive sulfated heteropolysaccharide with anti-inflammatory activity and might be a valuable candidate molecule for the treatment of allergic diseases such as ACD.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 839
Author(s):  
Boguen Kwon ◽  
SooYeon Hong ◽  
Eun-Young Kim ◽  
Jae-Hyun Kim ◽  
Minsun Kim ◽  
...  

Cone of Pinus densiflora (CP), or Korean red pinecone, is a cluster of Pinus densiflora fruit. CP has also been verified in several studies to have anti-oxidation, anti-fungal, anti-bacterial, and anti-melanogenic effects. However, anti-inflammatory effects have not yet been confirmed in the inflammatory responses of pinecones to allergic contact dermatitis. The purpose of this study is to prove the anti-inflammatory effect of CP on allergic contact dermatitis (ACD) in vitro and in vivo. CP inhibited the expression of TSLP, TARC, MCP-1, TNF-α, and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells and MCP-1, GM-CSF, TNF-α, IL-6, and IL-8 in PMACI (phorbol-12-myristate-13-acetate plus A23187)-stimulated HMC-1 cells. CP inhibited the phosphorylation of mitogen-activated protein kinase (MAPKs), as well as the translocation of NF-κB on TNF-α/IFN-γ stimulated in HaCaT cells. In vivo, CP decreased major symptoms of ACD, levels of IL-6 in skin lesion, thickening of the epidermis and dermis, infiltration of eosinophils and mast cells, and the infiltration of CD4+ T cells and CD8+ T cells. This result suggests that CP represents a potential alternative medicine to ACD for diseases such as chronic skin inflammation.


2005 ◽  
Vol 1 (1) ◽  
pp. 75-86 ◽  
Author(s):  
Marc Vocanson ◽  
Ana Hennino ◽  
Cyril Chavagnac ◽  
Pierre Saint-Mezard ◽  
Bertrand Dubois ◽  
...  

2017 ◽  
Vol 118 (1) ◽  
pp. 619-624 ◽  
Author(s):  
Lintao Qu ◽  
Kai Fu ◽  
Steven G. Shimada ◽  
Robert H. LaMotte

Persistent itch often accompanies allergic contact dermatitis (ACD), but the underlying mechanisms remain largely unexplored. We previously demonstrated that CXCL10/CXCR3 signaling activated a subpopulation of cutaneous primary sensory neurons and mediated itch response after contact hypersensitivity (CHS), a murine model of ACD, induced by squaric acid dibutylester. The purpose of this study was to determine the ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch. In whole cell recordings, CXCL10 triggered a current in dorsal root ganglion (DRG) neurons innervating the area of CHS. This current was modulated by intracellular Cl− and blocked by the general Cl− channel inhibitors. Moreover, increasing Ca2+ buffering capacity reduced this current. In addition, blockade of Cl− channels significantly suppressed CXCL10-induced Ca2+ response. In behavioral tests, injection of CXCL10 into CHS site exacerbated itch-related scratching behaviors. Moreover, the potentiating behavioral effects of CXCL10 were attenuated by either of two Cl− channel blockers. Thus we suggest that the Cl− channel acts as a downstream target mediating the excitatory and pruritic behavioral effects of CXCL10. Cl− channels may provide a promising therapeutic target for the treatment of allergic itch in which CXCL10/CXCR3 signaling may participate. NEW & NOTEWORTHY The ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch are largely unexplored. This study revealed that CXCL10 evoked an ionic current mainly carried by Cl− channels. We suggest that Cl− channels are likely key molecular candidates responsible for the CXCL10-evoked neuronal activation and itch-like behaviors in a murine model of allergic contact dermatitis induced by the antigen squaric acid dibutylester. Cl− channels may emerge as a promising drug target for the treatment of allergic itch in which CXCL10/CXCR3 signaling may participate.


2007 ◽  
Vol 127 (11) ◽  
pp. 2585-2595 ◽  
Author(s):  
Malene B. Pedersen ◽  
Lone Skov ◽  
Torkil Menné ◽  
Jeanne D. Johansen ◽  
Jørgen Olsen

2007 ◽  
Vol 127 (6) ◽  
pp. 1419-1429 ◽  
Author(s):  
Philippe Azam ◽  
Ananthakrishnan Sankaranarayanan ◽  
Daniel Homerick ◽  
Stephen Griffey ◽  
Heike Wulff

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