›› 2019, Vol. 46 ›› Issue (2): 608-620.doi: 10.16431/j.cnki.1671-7236.2019.02.033

• Basic Veterinary Medicine • Previous Articles     Next Articles

Pharmacodynamics and Molecular Mechanism Analysis of Zixiekang Oral Liquid

LUO Lirong1,2, CUI Dongan2, WANG Hui2, HAO Zhihui1, WANG Shengyi2   

  1. 1. Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Animal Husbandry and Pharmaceutical Science, Lanzhou 730000, China;
    2. College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830000, China
  • Received:2018-08-10 Online:2019-02-20 Published:2019-02-20

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Abstract:

The purpose of the experiment was to explore the pharmacodynamics and molecular mechanism of Zixiekang oral liquid in treating piglet diarrhea,and provide experimental basis for the further development of the drug.The pharmacological effects of Zixiekang oral liquid were verified by small intestinal propulsion test,diarrhea control test,ear swelling inhibition test,analgesic test and in vitro bacteriostasis test.Meanwhile,the active components of Zixiekang oral liquid were screened by network pharmacology.Target prediction and bioinformatics were used to determine the specific target of Zixiekang oral liquid for treating diarrhea.The molecular mechanism of the treatment of diarrhea was discussed by signal pathway enrichment analysis.The results showed that the anti-inflammatory and analgesic effects of Zixiekang oral liquid increased with the increase of dosage,and low dose of Zixiekang oral liquid had significant difference compared with blank control group (P<0.05);Compared with blank control group,the low,middle and high dose groups could all inhibit the propelling distance and pushing rate of small intestine carbon ink in mice,and the low dose group had significant difference (P<0.05).Zixiekang oral liquid had bacteriostasis effect on both Escherichia coli and Staphylococcus aureus,and had the more obvious effect on Escherichia coli.In this experiment,the antidiarrhea mechanism of Zixiekang oral liquid was predicted by network pharmacology,and it participated in Wnt signaling pathway to regulate the bacterial invasive epithelial cells,and also affected pathogenic Escherichia coli infection signal pathway;MAPK signaling pathway regulated the production of other inflammatory mediators by promoting or inhibiting the transcription of genes.At the same time,inflammatory mediators could increase the expression of various adhesion molecules on the cell surface by activating the MAPK pathway,and promote the progress of intercellular adhesion and inflammation.NRG/ErbB signal was involved in many aspects of neuropathic pain.In the central nervous system,microglia were activated by MEK/ERK pathway and a series of cytokines and inflammatory mediators were released to promote neuropathic pain.Neuropathic pain was also involved in neuropathic pain by regulating synaptic plasticity and central disinhibition.Peripheral nervous system,NRG/ErbB signal played an important role in analgesia by regulating the function of non-myelin forming cells and myelin forming Schwann cells and participating in ErbB signal of peripheral neuralgia.In summary,Zixiekang oral liquid might inhibit diarrhea from four aspects:Intestinal peristalsis,anti-inflammation,analgesia and bacteriostasis.

Key words: Zixiekang oral liquid; piglet diarrhea; systemic pharmacology; network pharmacology; molecular mechanism

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