Effect of kaempferol on hedgehog signaling pathway in rats with ‐‐chronic atrophic gastritis – Based on network pharmacological screening and experimental verification

Abstract

The effect of active ingredients of Chaishaoliujun Decoction (CD) on chronic atrophic gastritis (CAG) was screened by network pharmacological method and verified by preliminary experiment.Firstly, the active ingredients and drug targets of CD were retrieved in TCMSP database; CAG-related targets from PharmGkb, OMIM, GeneCards and DrugBank databases were collected as well. Secondly, the drug targets and disease targets were mapped to obtain the intersection targets. PPI network and active ingredient-common target network were constructed for the intersection targets obtained and KEGG enrichment analysis was also carried out. Finally, the core active ingredient (kaempferol), effective targets (IL-1β、IL-6) and hedgehog signaling pathway were verified by animal experiments.There were 137 active ingredients, 243 potential target so and 48 intersection targets with CAG in CD. 147 KEGG enrichment pathways were obtained, mainly involving JAK/STAT signaling pathway, PI3K/Akt signaling pathway, hedgehog signaling pathway, etc. The results of animal experiments showed: The content of IL-1β and IL-6 in model group was significantly increased compared with the normal group, while the mRNA and protein expressions of Shh, Ptch1 and Gli1 were also significantly decreased (P < 0.05); compared with model group, the content of IL-1β and IL-6 in the vitacoenzyme group, the CD group and the kaempferol group were significantly decreased, while the mRNA and protein expressions of Shh, Ptch1 and Gli1 were significantly increased (P < 0.05).Kaempferol, the active ingredient of CD, could reduce the levels of IL-6 and IL-1β by regulating hedgehog signaling pathway so as to play a role in the treatment of CAG. Hence this paper could provide the methodological basis and theoretical basis for further revealing the pharmacological mechanism of CD.