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Efficacy and Mechanism of Action of Ermiao Situ Decoction in Modulating JAK/STAT Pathway in Rats with Damp-heat Eczema

  • role： First author第一作者
  • Affiliation：

    Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine，School of Pharmacy， Hubei University of Chinese Medicine，Wuhan 430065，China

  • Email：1968359096@qq.com
  • Introduction：韩康宁，在读硕士，从事中药药效物质基础研究，E-mail：1968359096@qq.com
HAN Kangning1,  
  • Affiliation：

    Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine，School of Pharmacy， Hubei University of Chinese Medicine，Wuhan 430065，China

HU Junjie1,  
  • Affiliation：

    Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine，School of Pharmacy， Hubei University of Chinese Medicine，Wuhan 430065，China

LI Juan1,  
  • Affiliation：

    Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine，School of Pharmacy， Hubei University of Chinese Medicine，Wuhan 430065，China

ZHANG Min1,  
  • Affiliation：

    Clinical College of Chinese Medicine，Hubei University of Chinese Medicine，Wuhan 430060，China

ZHOU Xian2,  
  • role： Corresponding author通信作者
  • Affiliation：

    Clinical College of Chinese Medicine，Hubei University of Chinese Medicine，Wuhan 430060，China

  • Email：newforest@163.com
  • Introduction：刘松林，博士，教授，从事经方防治消化及心血管疾病的临床基础研究，E-mail：newforest@163.com； *
LIU Songlin2*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine，School of Pharmacy， Hubei University of Chinese Medicine，Wuhan 430065，China

  • Email：chenxin30172@hotmail.com
  • Introduction：陈新，博士，副研究员，从事中药药效物质基础研究，E-mail：chenxin30172@hotmail.com
CHEN Xin1*

Resümee

ObjectiveUltra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS） coupled with network pharmacology and molecular docking was utilized to explore the efficacy and mechanism of action of Ermiao Situ decoction on rats with damp-heat eczema.MethodsA rat model of damp-heat eczema was established by artificial climate chamber intervention combined with sensitization induction by dinitrochlorobenzene （DNCB）， and it was randomly divided into the normal group， the model group， the medium- and high-dose groups of Ermiao Situ decoction （3.40 g·kg-1 and 6.80 g·kg-1）， and the prednisone acetate group （2.51 mg·kg-1）， with eight rats in each group， totalling 46 rats， of which six rats were tested with the drug-containing serum. The chemical analysis of drug-containing serum from rats was carried out by UPLC-Q-TOF-MS/MS， combined with network pharmacology for the prediction of key components， core targets， and signaling pathways， and molecular docking experiments were performed by CB-Dock2 online website. The pharmacological effects of Ermiao Situ decoction in the treatment of damp-heat eczema were investigated by epitaxial indexes combined with the pathologic tissue staining method. The serum levels of gastrin （GAS）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured by enzyme-linked immunosorbent assay （ELISA）. Interleukin-6 （IL-6）， Janus kinase 1 （JAK1）， phosphorylated （p）-JAK1， signal transduction and activation of transcription factor 3 （STAT3）， and p-STAT3 protein expression level was determined by Western bolt.ResultsA total of 19 active ingredients were detected in drug-containing serum samples of rats， which were predicted to act on 198 targets for the treatment of damp-heat eczema， among which the key ingredients included rhodopsin， huangpai alkaloids， and quercetin， and the main core targets included STAT3， tumor necrosis factor （TNF）， and IL-6， which were mainly involved in the cancer signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase （Akt） signaling pathway， T helper 17 （Th17） cell differentiation signaling pathway， and JAK/STAT signaling pathway. The molecular docking results suggested that the key components had strong binding activities with the core targets IL-6， JAK1， and STAT3 in the JAK/STAT signaling pathway. The results of animal experiments showed that compared with those in the normal group， rats in the model group were depressed. They had loose hair， loose stools， epidermal oozing， vesiculation， and generation of thick scabs in the form of scales， decreased body weight， increased anus temperature and water intake， and increased indexes of the spleen， thymus gland， and stomach （P<0.05， P<0.01）， and the lesion tissue could be seen to be hyperkeratotic， with the aggregation of inflammatory cells and nonsignificant separation of epidermis and dermis. The gastric mucosa was thinned， deficient， and structurally disorganized， and obvious inflammatory cell aggregation was seen. The levels of GAS， IL-4， and IL-13 in serum were significantly reduced （P<0.05， P<0.01）， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the lesion tissue were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， rats in each administration group had stable mental states， formed feces， a clean perianal area， and basically normal epidermis. Only a small amount of scaly scabs existed， and the rats had body weight increased， with decreased anal temperature and water intake， as well as decreased spleen， thymus， and gastric indexes （P<0.05， P<0.01）. Epidermal thickness was decreased， and epidermal and dermal separation boundaries were obvious， but hyperkeratotic and accumulation of inflammatory cells could still be seen. The thickness of gastric mucosa increased， and the structure was restored to varying degrees. The levels of GAS， IL-4， and IL-13 content in the serum of rats were increased to varying degrees， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the dermal lesion tissue were significantly decreased （P<0.05， P<0.01）.ConclusionErmiao Situ decoction may exert therapeutic effects on rats with damp-heat eczema by modulating the JAK/STAT signaling pathway.

Schlüsselwort

Ermiao Situ decoction;damp-heat eczema;ultra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）;network pharmacology;Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway

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