Exploring Regulatory Effect of Kaixuan Jiedu Core Prescription on SPHK2/S1P/MCP-1 Pathway in Psoriasis-like Mouse Model Based on Sphingolipid Metabolism
10.13422/j.cnki.syfjx.20250237
- VernacularTitle:基于鞘脂代谢探索开玄解毒核心方对银屑病样小鼠皮损SPHK2/S1P/MCP-1通路的调控作用
- Author:
Yeping QIN
1
;
Wenhui LIU
2
;
Dan DAI
3
;
Jia XU
3
;
Chong LI
4
;
Bin YANG
1
;
Ping SONG
1
Author Information
1. Xiyuan Hospital， China Academy of Chinese Medical Sciences， Beijing 100091， China
2. Liaocheng People's Hospital， Liaocheng 252000， China
3. Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Beijing 100053， China
4. Institute of Biophysics， Chinese Academy of Sciences， Beijing 100101， China
- Publication Type:Journal Article
- Keywords:
Kaixuan Jiedu core prescription;
multi-omics analysis;
sphingolipid metabolism;
psoriasis vulgaris;
sphingosine kinase 2 （SPHK2）/sphingosine-1-phosphate （S1P）/monocyte chemotactic protein-1 （MCP-1） pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(17):60-68
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg-1） KXJD （n=5）， and high-dose （30.42 g·kg-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.
