Publications

@article{Kim2026,

title = {Vitexin alleviates atopic dermatitis–associated itch via TRPV4 inhibition in sensory neurons and MRGPRX2/MrgprB2 blockade in mast cells},

author = {Yejoon Kim and Junhyeok Choi and Minjun Kim and Diwas Rawal and Wook-Joo Lee and Won-Sik Shim},

doi = {10.1016/j.intimp.2025.115757},

issn = {1567-5769},

year  = {2026},

date = {2026-01-00},

urldate = {2026-01-00},

journal = {International Immunopharmacology},

volume = {168},

publisher = {Elsevier BV},

abstract = {Chronic itch is a debilitating symptom in atopic dermatitis (AD), often resistant to current antipruritic therapies. Here, we demonstrate that vitexin (VTX) exerts antipruritic effects through modulation of neuronal and mast cell pathways. Calcium imaging in TRPV4-transfected HEK293T cells and primary mouse dorsal root ganglion neurons demonstrated that VTX substantially inhibited TRPV4-dependent calcium influx, reducing both peak responses and the proportion of agonist-responsive neurons. Parallel assays in HEK293T cells expressing human MRGPRX2 and murine MrgprB2 revealed dose-dependent suppression of compound 48/80-induced calcium signaling. Mast-cell degranulation assays indicated that VTX markedly decreased β-hexosaminidase release from primary mouse peritoneal mast cells and HMC1.2 cells upon compound 48/80 stimulation. In silico molecular docking analysis showed that VTX occupied overlapping binding regions with known agonists in TRPV4 and MRGPRX2/MrgprB2, suggesting direct receptor interactions. In an MC903-induced murine model of AD, VTX reduced scratching behavior, mast cell activation, and transcriptional upregulation of Trpv4 and MrgprB2. Notably, antipruritic effects were enhanced in Trpv4-deficient mice, indicating the contribution of MRGPRX2/MrgprB2 suppression. These findings identify VTX as a promising antipruritic candidate for AD-associated pruritus, and mechanistic insights provide a rationale for further exploration of VTX in advanced AD models and eventual translation to clinical therapies.},

keywords = {Atopic dermatitis, Itch, Mast cell, MrgprB2, MRGPRX2, Sensory neurons, TRPV4},

pubstate = {published},

tppubtype = {article}

}

@article{Sanjel2025,

title = {Identification of KMH-45, a novel MRGPRX2 inhibitor with enhanced anti-pruritic properties},

author = {Babina Sanjel and Mahesh kumar Teli and Surendra Kumar and Ji-Hoon Oh and Han-Joo Maeng and Won-Sik Shim and Mi-hyun Kim},

doi = {10.1016/j.biopha.2025.118371},

issn = {0753-3322},

year  = {2025},

date = {2025-09-00},

urldate = {2025-09-00},

journal = {Biomedicine & Pharmacotherapy},

volume = {190},

publisher = {Elsevier BV},

keywords = {Itch, MRGPRX2, Scratching behavior},

pubstate = {published},

tppubtype = {article}

}

@article{Cha2024,

title = {Antipruritic effect of ursolic acid through MRGPRX2/MrgprB2-dependent inhibition of mast cell degranulation and reduced TSLP production},

author = {Jieun Cha and Juhee Ryu and Diwas Rawal and Wook-Joo Lee and Won-Sik Shim},

doi = {10.1016/j.ejphar.2024.176896},

issn = {0014-2999},

year  = {2024},

date = {2024-10-00},

urldate = {2024-10-00},

journal = {European Journal of Pharmacology},

volume = {981},

publisher = {Elsevier BV},

keywords = {Mast cell, MrgprB2, MRGPRX2, TSLP, Ursolic acid},

pubstate = {published},

tppubtype = {article}

}

@article{Adhikari2024,

title = {A phytosphingosine derivative mYG-II-6 inhibits histamine-mediated TRPV1 activation and MRGPRX2-dependent mast cell degranulation},

author = {Nisha Adhikari

Wook-Joo Lee

Soojun Park

Sanghee Kim 

Won-Sik Shim},

doi = {10.1016/j.intimp.2024.112113},

issn = {1567-5769},

year  = {2024},

date = {2024-05-00},

urldate = {2024-05-00},

journal = {International Immunopharmacology},

volume = {133},

publisher = {Elsevier BV},

keywords = {Histamine, Mast cell, MRGPRX2, TRPV1},

pubstate = {published},

tppubtype = {article}

}

@article{Adhikari2022,

title = {Caffeic acid phenethyl ester inhibits pseudo-allergic reactions via inhibition of MRGPRX2/MrgprB2-dependent mast cell degranulation},

author = {Nisha Adhikari and Won-Sik Shim},

doi = {10.1007/s12272-022-01405-2},

issn = {1976-3786},

year  = {2022},

date = {2022-09-00},

urldate = {2022-09-00},

journal = {Arch. Pharm. Res.},

volume = {45},

number = {9},

pages = {644--657},

publisher = {Springer Science and Business Media LLC},

abstract = {Mast cells play essential role in allergic reactions through the process called mast cell degranulation. Recent studies have found that a basic secretagogue compound 48/80 (C48/80) induces non-IgE-mediated mast cell degranulation via activation of human Mas-related G protein-coupled receptor X2 (MRGPRX2) and mouse MrgprB2. Although previous studies have revealed that caffeic acid (CA) and its derivatives possess anti-allergic effects via IgE-dependent manner, it is largely elusive whether these compounds have impact on MRGPRX2/MrgprB2 to exert inhibitory effects. Therefore, the present study investigated whether CA as well as its derivatives - rosmarinic acid (RA) and caffeic acid phenethyl ester (CAPE) - has the ability to inhibit the activity of MRGPRX2/MrgprB2 to evoke pseudo-allergic effects. As a result, it was found that CAPE inhibits C48/80-induced activation of MRGPRX2/MrgprB2, but neither CA nor RA showed discernible inhibition. Furthermore, the β-hexosaminidase release assay showed that CAPE inhibits mouse peritoneal mast cell degranulation in both IgE-dependent and MrgprB2-dependent manners. Additionally, mouse paw edema induced by C48/80 was dramatically suppressed by co-treatment of CAPE, suggesting that CAPE possesses a protective effect on C48/80-evoked pseudo-allergic reactions. The pretreatment of CAPE also significantly decreased scratching bouts of mice evoked by C48/80, demonstrating that CAPE also has an anti-pruritic effect. Therefore, these data implicate that CAPE can suppress pseudo-allergic reactions evoked by C48/80 via MrgprB2-dependent manner. Finally, molecular docking analysis showed that CAPE is predicted to bind to human MRGPRX2 in the region where C48/80 also binds, implying that CAPE can be a competitive inhibitor of MRGPRX2. In conclusion, it is found that CAPE has the ability to inhibit MRGPRX2/MrgprB2, leading to the prevention of mast cell degranulation and further to the alleviation of mast cell reactions. These results indicate that CAPE as a CA derivative could be developed as a new protective agent that exerts dual inhibition of mast cell degranulation mediated by IgE and MRGPRX2/MrgprB2.},

keywords = {Allergy, Calcium imaging, Mast cell, MrgprB2, MRGPRX2},

pubstate = {published},

tppubtype = {article}

}