Kaixuan Jiedu Core Prescription Alleviates Restraint Stress-exacerbated Imiquimod-induced Psoriasis-like Skin Lesions via Regulation of HPA Axis and Neuroinflammation
10.13422/j.cnki.syfjx.20260631
- VernacularTitle:开玄解毒核心方通过调控HPA轴与神经炎症缓解束缚应激加重的IMQ诱导银屑病样皮损
- Author:
Ningxin ZHANG
1
;
Haoruo YANG
2
;
Jiaqi LI
1
;
Mengyao JIANG
3
;
Jiarong WU
1
;
Xinqian LIU
1
;
Bin YANG
1
;
Ping SONG
1
Author Information
1. Xiyuan Hospital of China Academy of Chinese Medical Sciences， Beijing 100091， China
2. Tianjin University of Traditional Chinese Medicine， Tianjin 301617， China
3. Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Beijing 100053， China
- Publication Type:Journal Article
- Keywords:
Kaixuan Jiedu core prescription （KXJD）;
psoriasis;
restraint stress;
hypothalamic-pituitary-adrenal axis;
inflammation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(19):79-88
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the ameliorative effect and potential mechanisms of Kaixuan Jiedu core prescription （KXJD） on imiquimod （IMQ）-combined restraint stress-induced psoriasis-like skin lesions in mice. MethodsA total of 36 C57BL/6J mice were randomly assigned to six groups （n=6 per group）： Normal group， restraint stress blank group， model group， restraint stress model group， KXJD group （30.42 g·kg-1）， and methotrexate group （0.001 g·kg-1）. Psoriasis-like lesions were induced by topical IMQ application combined with restraint stress. After 5 days of intervention， the severity of skin lesions was evaluated using the Psoriasis Area and Severity Index （PASI）. The following parameters were assessed： Hypothalamic-pituitary-adrenal （HPA） axis-related hormones， including adrenocorticotropic hormone （ACTH）， corticotropin-releasing hormone （CRH）， and corticosterone （CORT）， central neuronal markers， including neuronal nuclei antigen （NeuN）， microtubule-associated protein 2 （MAP2）， and beta Ⅲ-tubulin （β-Ⅲ tubulin）， microglial activation markers， including ionized calcium-binding adapter molecule-1 （Iba-1） and cluster of differentiation 11b （CD11b）， and skin nerve fiber markers， including protein gene product 9.5 （PGP9.5） and serotonin （5-HT）， as well as the expression levels of inflammatory cytokines tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， and interleukin-1 beta （IL-1β）. ResultsCompared with the normal group， both the model group and the restraint stress model group exhibited more severe psoriasis-like skin lesions， with significantly elevated serum levels of ACTH， CRH， and CORT （P<0.01）. The expression of glucocorticoid receptor （GR） and corticotropin-releasing hormone receptor 1 （CRHR1） in the skin was significantly downregulated. The expression of NeuN， MAP2， β-Ⅲ tubulin， Iba-1， and CD11b in the hypothalamus and hippocampus was significantly upregulated， suggesting abnormal changes in neuronal number or structure and aberrant activation of glial cells （P<0.05， P<0.01）. In addition， the expression of PGP9.5 and 5-HT in the skin， as well as the mRNA levels of TNF-α， IL-6， and IL-1β were all markedly elevated （P<0.05， P<0.01）. Compared with the model group， the restraint stress model group showed further exacerbation in most parameters. Compared with the restraint stress model group， the KXJD group exhibited significantly reduced PASI scores （P<0.01）， significantly decreased serum CRH， ACTH， and CORT levels （P<0.05， P<0.01）， upregulated skin GR and CRHR1 expression， inhibited abnormal neuronal changes and microglial activation in the hypothalamus and hippocampus， attenuated skin nerve fiber hyperplasia and amine signaling molecule release， and significantly reduced pro-inflammatory cytokine mRNA expression （P<0.05， P<0.01）. ConclusionKaixuan Jiedu Core prescription can effectively ameliorate IMQ combined with restraint stress-induced psoriasis-like skin lesions in mice by modulating HPA axis function， inhibiting central neuropathological changes， and attenuating skin nerve fiber hyperplasia， amine signaling molecule （5‑HT） release and local inflammatory responses.
