Kaixuan Jiedu Core Prescription Ameliorates Imiquimod-induced Psoriasis-like Skin Lesions in Mice by Inhibiting Neuroinflammation Mediated by NGF-TrkA/TRPV1-PAR-2 Signaling Pathway
10.13422/j.cnki.syfjx.20261121
- VernacularTitle:开玄解毒核心方通过抑制NGF-TrkA/TRPV1-PAR-2信号通路介导的神经炎症治疗咪喹莫特诱导的银屑病样小鼠
- Author:
Mengyao JIANG
1
;
Jiaqi LI
1
;
Huan LIU
1
;
Xue XIAO
1
;
Ningxin ZHANG
1
;
Bin YANG
1
;
Ping SONG
1
Author Information
1. Xiyuan Hospital， China Academy of Chinese Medical Sciences， Beijing 100091， China
- Publication Type:Journal Article
- Keywords:
Kaixuan Jiedu core prescription;
psoriasis;
neuroinflammation;
nerve growth factor-tropomyosin receptor kinase A/transient receptor potential vanilloid 1-protease-activated receptor-2 （NGF-TrkA/TRPV1-PAR-2） signaling pathway;
p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor-κB （NF-κB） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(19):111-119
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects and molecular mechanisms of Kaixuan Jiedu core prescription （KXJD） on neuroinflammation and immuno-inflammation in the mouse model of imiquimod （IMQ）-induced psoriasis-like skin lesions by regulating the nerve growth factor （NGF）-tropomyosin receptor kinase A （TrkA）/transient receptor potential vanilloid 1 （TRPV1）-protease-activated receptor-2 （PAR-2） signaling pathway. MethodsA psoriasis-like skin lesion model was established in male C57BL/6J mice with IMQ. A total of 24 mice were randomized into four groups （n=6 per group）： Blank control， model， methotrexate （MTX， 1 mg·kg-1）， and KXJD （30.42 g·kg-1）. Immunohistochemistry was employed to detect the expression of cluster of differentiation 3 （CD3）， EGF-like module-containing mucin-like hormone receptor-like 1 （F4/80）， lymphocyte antigen 6 complex locus G （Ly-6G）， substance P （SP）， calcitonin gene-related peptide （CGRP）， NGF， phosphorylated TrkA （p-TrkA）， phosphorylated TRPV1 （p-TRPV1）， and PAR-2 in skin lesions. Serum levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23） were measured by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence assay and Western blot were employed to determine the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65）. Reverse transcription quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and C-X-C motif chemokine ligand 1 （CXCL1） in skin lesions. Correlation analysis was performed. ResultsCompared with the blank control group， the model group showed increased positive areas of CD3+， F4/80+， and Ly-6G+ in skin lesions （P<0.05）， elevated serum levels of IL-17A and IL-23 （P<0.05）， increased positive areas of SP and CGRP in skin lesions （P<0.05）， increased positive areas of NGF， p-TrkA， p-TRPV1， and PAR-2 （P<0.05）， elevated ratios of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.05）， and upregulated mRNA levels of IL-1β， TNF， IL-6， and CXCL1 （P<0.05）. Compared with those in the model group， all the above indicators were reversed in the KXJD group （P<0.05）. MTX only downregulated the expression of p-TRPV1 and PAR-2 （P<0.05）， with no significant effects on the expression of NGF， p-TrkA， or CGRP. ConclusionKXJD inhibits the NGF-TrkA/TRPV1-PAR-2 signaling pathway to reduce neuropeptide release and simultaneously downregulates the p38 MAPK/NF-κB signaling pathway and the expression of downstream pro-inflammatory factors to ameliorate psoriasis-like neuroinflammation and immuno-inflammation. The therapeutic effect of KXJD on psoriasis-like inflammation is closely associated with the inhibition of the NGF-TrkA/TRPV1-PAR-2 signaling pathway. This study provides experimental evidence for the modern interpretation of the Xuanfu theory.
