Therapeutic effect of Baoyuan Decoction on ISO-induced chronic heart failure in rats based on network pharmacology and experimental validation
OBJECTIVE To explore the therapeutic effect of Baoyuan Decoction(BYD)on isoproterenol(ISO)-induced chronic heart failure(CHF)rats based upon fingerprinting-network pharmacology-molecular docking technique and experimental validations.METHODS High performance liquid chromatography(HPLC)was utilized for establishing the baseline fingerprints and determining the contents of BYD.Network pharmacology was employed for constructing the"active ingredient-target-disease"network,GO enrichment analysis and KEGG pathway enrichment analysis and molecular docking validation of key active ingredi-ents and key targets.Using Autodock Tools software,the authors initially determined the active ingredient and the potential thera-peutic mechanism of BYD for CHF.CHF model of Sprague-Dawley rats was established by ISO dose gradient decreasing method.The rats were grouped and received the corresponding drugs by a 4-week gavage.All parameters were recorded.The animals were sacrificed at the end of drug dosing.The samples were subjected to the detection of cardiac enzyme-related factors,myocardial histopathology and immunohistochemistry.RESULTS The similarity of baseline fingerprints of 10 batches of BYD was greater than 0.900.It indicated that the established fingerprint method could be used for identification and quality control of BYD.The network pharmacology results showed 5 key active ingredients and 11 key targets in BYD,involving the major signal-ing pathways of cellular responses to chemical stress and AGE-RAGE in diabetic complications and apoptosis.Molecular docking results showed that quercetin,kaempferol and isorhamnetin and key compounds in BYD had potent binding activities with all key targets.The results of cardiac weight index,enzyme-linked immunosorbent assay(ELISA)kit and hematoxylin-eosin/Masson stain showed the same results of marked myocardial injury after modeling.It proved that modeling was successful and injury less-ened in dosing group.There was no significant difference in low-dose group.The efficacy of high-dose group was significantly bet-ter than that of low-dose group.There was a significant difference in the ratio of model group.Immunohistochemical results revealed that ISO modeling group showed a significant up-regulation of Bax and caspase-3 protein expression and a down-regulation of Bcl-2 expression as compared to blank group.There was non-significant improvement in low-dose group.The expressions of Bax and caspase-3 were down-regulated while the expression of Bcl-2 was up-regulated in high-dose group.CONCLUSION The mechanisms of action of active ingredients of BYD for CHF are mediated through multi-target regulation and participating in multiple information pathways and biological processes.
NETL
NSTL
万方数据
