The Mechanism of Xiaoluo Pills Combined with Codonopsis Radix in the Treatment of Goiter Based on Network Pharmacology and Animal Experiments
Objective To explore the mechanism of Xiaoluo pills combined with Codonopsis Radix in the treat-ment of goiter based on animal experiments and network pharmacology.Methods(1)Active ingredients and potential tar-gets of Xiaoluo pills combined with Codonopsis Radix were screened through the TCMSP database,while goiter(GR)-rel-evant targets were retrieved from the GeneCards database.The intersecting targets between the active ingredients and GR disease targets were identified using Venny 2.1.0,resulting in the intersecting targets for Xiaoluo pills combined with Codonopsis Radix in treating GR.A"Xiaoluo pills combined with Codonopsis Radix-active ingredients-intersecting tar-gets"network was constructed using Cytoscape 3.8.0 to analyze key active ingredients.The intersecting targets were impor-ted into the STRING database to build a protein-protein interactions(PPI)network,from which core targets were screened.GO function and KEGG enrichment analyses were performed using the R package,and PyMol software was used to show the binding conformations between the best active ingredients and all the targets.(2)The predicted results were verified through animal experiments.Thirty-four male Wistar rats(6-8 weeks old,SPF-grade)were purchased,with 8 rats ser-ving as the normal group.The remaining rats were administered with propylthiouracil(PTU)solution to induce the GR rat model.After successful modeling,the rats were randomly divided into the model group,positive drug group,Xiaoluo pills group,Xiaoluo pills combined with Codonopsis Radix group,with 6 rats in each group.The normal group was given daily gavage with an equal amount of distilled water.After modeling,the model group was given distilled water by gavage;the positive drug group was given Euthyrox solution by gavage;the Xiaoluo pills group was given Xiaoluo pills solution by ga-vage;Xiaoluo pills combined with Codonopsis Radix was given both Xiaoluo pills and Codonopsis Radix by gavage.After 6 weeks of intervention,the rats were sacrificed following isoflurane anesthesia.Pathological tissue observations were conduc-ted,and enzyme-linked immunosorbent assay(ELISA)was used to measure levels of triiodothyronine(T3),tetraiodothyro-nine(T4),and thyroid-stimulating hormone(TSH).Western blot(WB)analysis was performed to detect the protein ex-pression of phosphoinositide 3-kinase(PI3 K),protein kinase B(Akt),and B-cell lymphoma-2(Bel-2).Results(1)42 active ingredients and 96 intersecting targets were identified for Xiaoluo pills combined with Codonopsis Radix in treating GR.KEGG enrichment analysis showed that Xiaoluo pills combined with Codonopsis Radix may exert effects through the Akt/PI3K signaling pathway and apoptosis.(2)Animal experiment data showed that in the positive drug group,Xiaoluo pills group,and Xiaoluo pills combined with Codonopsis Radix group,thyroid follicular swelling,surrounding hyperplasia,stromal congestion,and the internal papillary structures were reduced,with the most significant thyroid follicu-lar recovery and epithelial cell restoration observed in the Codonopsis Radix group.Compared with the normal group,TSH levels,PI3 K,Akt,and Bel-2 protein expression in the model group,were significantly elevated,with a statistically signifi-cant difference(P＜0.05).Compared to the model group,TSH levels,PI3K,and Bel-2 protein expression in the Codo-nopsis Radix group were significantly reduced,with statistically significant differences(P＜0.05);T3 and T4 hormone lev-els in the Codonopsis Radix group were increased.Conclusion Xiaoluo pills combined with Codonopsis Radix can exert therapeutic effects on GR by targeting Bcl-2 and participating in the PI3K/Akt signaling pathway.
GoiterNetwork PharmacologyAnimal ExperimentsXiaoluo Pills Combined with Codonopsis Radix
万方数据
维普
