Publications

@article{Lee2023,

title = {Rg3-enriched Korean red ginseng alleviates chloroquine-induced itch and dry skin pruritus in an MrgprA3-dependent manner in mice},

author = {Wook-Joo Lee and Won-Sik Shim},

doi = {10.1016/j.imr.2022.100916},

issn = {2213-4220},

year  = {2023},

date = {2023-03-00},

urldate = {2023-03-00},

journal = {Integrative Medicine Research},

volume = {12},

number = {1},

publisher = {Elsevier BV},

abstract = {Background: Previous studies have found that Korean red ginseng extract (KRG) has antipruritic effects, which can be attributed to the presence of Rg3, one of the most potent ginsenosides. Therefore, Rg3-enriched KRG extract (Rg3EKRG) is anticipated to have enhanced antipruritic effects. The present study was conducted to examine the effects of Rg3EKRG in acute chloroquine (CQ)-induced and chronic dry skin pruritus.



Methods: Calcium imaging technique was used in HE293T cells expressing MrgprA3 and TRPA1 ("MrgprA3/TRPA1") and in primary cultures of mouse dorsal root ganglia (DRG) neurons. Mouse scratching behavior tests were performed on dry skin models. To verify the altered expression of itch-related genes, real-time RNA sequencing analysis and PCR were performed on DRG sections obtained from dry skin models.



Results: Rg3EKRG suppressed CQ-induced intracellular calcium changes to a greater degree than KRG. Rg3EKRG dose-dependently inhibited CQ-induced responses in MrgprA3/TRPA1 cells. Rg3EKRG likely targeted MrgprA3 rather than TRPA1 to exert its inhibitory effect. Further, Rg3EKRG strongly inhibited the scratching behavior in mice induced by acute CQ injection. Importantly, DRG neurons obtained from dry skin mice models showed increased mRNA levels of MrgprA3, and treatment with Rg3EKRG alleviated chronic dry skin conditions and suppressed spontaneous scratching behaviors.



Conclusion: The results of the present study imply that Rg3EKRG has a stronger antipruritic effect than KRG, inhibiting both acute CQ-induced and chronic dry skin pruritus in an MrgprA3-dependent manner. Therefore, Rg3EKRG is a potential antipruritic agent that can suppress acute and chronic itching at the peripheral sensory neuronal level.},

keywords = {Dry skin, Itch, Korean Red Ginseng, MrgprA3, RNA-seq, Scratching behavior, TRPA1},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2021,

title = {Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus},

author = {Wook-Joo Lee and Won-Sik Shim},

doi = {10.3389/fimmu.2021.772941},

issn = {1664-3224},

year  = {2021},

date = {2021-12-02},

urldate = {2021-12-02},

journal = {Front. Immunol.},

volume = {12},

publisher = {Frontiers Media SA},

abstract = {<jats:p>Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in <jats:italic>Trpv4</jats:italic> knockout (KO) mice following treatment with AEW. The increase in the intracellular calcium levels by TSLP in the dorsal root ganglia (DRG) of <jats:italic>Trpv4</jats:italic> KO mice was also significantly attenuated. The spontaneous scratching bouts were significantly decreased in both the HC067047-treated and <jats:italic>Trpv4</jats:italic> KO AEW mice. Importantly, the TSLP-dependent release of tryptase from the mast cells was significantly reduced in both the HC067047-treated mice and <jats:italic>Trpv4</jats:italic> KO AEW mice. Notably, inhibition of the TSLP-induced signaling pathway in DRG selectively reduced the spontaneous scratching bouts in AEW mice. Overall, the results demonstrated that the cutaneous neuroimmune interactions of TSLP and TRPV4 play pivotal roles in dry skin-induced pruritus.</jats:p>},

keywords = {Calcium imaging, Dorsal root ganglia, Dry skin, Itch, TSLP},

pubstate = {published},

tppubtype = {article}

}