Mechanism of Elian Granules modulating JAK2/STAT3 pathway for treatment of chronic atrophic gastritis
Objective To explore the effect of Elian Granules on the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in rats with chronic atrophic gastritis(CAG)using transcriptomic sequencing,and to elucidate the mechanisms behind its therapeutic action.Methods Eighteen 6-week-old male Sprague-Dawley(SD)rats were acclimatized for one week and then divided into three groups:a normal group,a model group,and an Elian Granules group.Apart from the normal control group,the model group and the Elian Granules group were induced with chronic atrophic gastritis using the N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)synthesis method.The Elian Granules group was administered an oral gavage of Elian Granules solution at a dosage of 3.24 g/kg.The intervention lasted for 40 weeks.The pathological morphology of rat gastric tissues was detected using Hematoxylin-Eosin(HE)staining;transcriptomics was performed for library sequencing and raw signal analysis,and JAK2,phosphorylated Janus kinase 2(p-JAK2),STAT3,phosphorylated signal transducer and activator of transcription 3(p-STAT3),suppressor of cytokine signaling 3(SOCS3),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)protein expression were detected using Western blot in each group of rat gastric sinus tissues.Results The epithelial structure of the gastric mucosa was intact in the control group of rats,and the glands had normal morphology and were arranged in a neat and regular manner.In the model group,the gastric mucosal glands of rats were atrophied,with disorderly arrangement.In contrast,in the Elian Granules group,the glandular morphology was maintained relatively intact with regular arrangement.Compared to the normal group,the model group expressed 3,595 differentially regulated genes(DEGs),including 1,203 upregulated and 2,392 downregulated genes.Compared to the model group,the Elian Granules group exhibited 561 DEGs,including 174 upregulated and 387 downregulated genes.Enrichment analysis through Kyoto Encyclopedia of Genes and Genomes(KEGG)suggested that the mechanisms of CAG intervention by Elian Granules might be closely associated with signaling pathways such as chemokine signaling pathway,PI3K-Akt signaling pathway,and oncogenic pathways.Western blot results indicated that compared to the control group,the model group had significantly higher expression of p-JAK2,p-STAT3,and Bcl-2 proteins(P<0.01,P<0.001),and significantly lower SOCS3 and Bax proteins(P<0.01).The Elian Granules group showed significant reductions in p-JAK2,p-STAT3,and Bcl-2 protein expressions compared to the model group(P<0.01,P<0.001),with a significant increase in SOCS3 and Bax protein expressions(P<0.05).Conclusion In this study,we successfully replicated the CAG rat model using the MNNG synthesis method,and with the help of transcriptomic sequencing and validation,we found and empirically demonstrated that Elian granules may be able to treat CAG by inhibiting the JAK2/STAT3 pathway.
chronic atrophic gastritisElian granulesmechanism of actionrat modeltraditional Chinese herbal medicine research
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