Based on metabolomics and network pharmacology mechanism of Astragali Radix-Polygonati Odorati Rhizoma-Ganoderma in treatment of chronic bronchitis
Objective To investigate the mechanism of action of"Astragali Radix-Polygonati Odorati Rhizoma-Ganoderma"(HYL)in the treatment of chronic bronchitis(CB)using serum metabolomics,network pharmacology and molecular docking techniques.Methods A chronic bronchitis model was established in SD rats by smoking method,and the successful rats were randomly divided into the model group,the positive drug group(Ambroxol Hydrochloride Dispersible Tablets 0.92 mg·kg-1),the HYL high-,mid-,low-doses(10.71,3.57,1.19 g·kg-1)groups,and the enzyme-linked immunosorbent assay(ELISA)was used to determine the inflammatory factors interleukin 8(IL-8),tumor necrosis factor(TNF-α),and nitric oxide(NO)in the serum of the rats,substance P(SP)expression levels in lung tissues.The metabolic profiles of rat serum were analyzed by UPLC-Q/TOF-MS/MS,and the differential metabolites and related metabolic pathways were screened.The"ingredient-target-pathway-disease"diagram of HYL for CB treatment was constructed by network pharmacology.The molecular docking method was used to verify the interaction between the active ingredients and the core targets.Serum metabolomics and network pharmacology were combined to construct a"target-metabolic pathway-metabolite"network diagram.Results HYL significantly reduced the levels of IL-8,TNF-α and SP,and increased the level of NO in the serum of rats.Twenty differential metabolites were screened out from serum by metabolomics,and HYL was able to regulate the levels of these differential metabolites compared with those in the model group.Five key metabolic pathways(cytochrome P450,folate synthesis,sphingolipid metabolism,steroid hormone biosynthesis,and pentose and glucuronide interconversion)were screened.Network pharmacological analyses showed that HYL therapeutic CB mainly acted on target proteins such as PIK3CA,MAPK3 and MAPK1,which are closely related to signaling pathways such as cancer pathways,lipids and atherosclerosis.Integrative analysis showed that cytochrome P450 and steroid hormone biosynthesis metabolism were the key metabolic pathways in HYL treatment of CB.Conclusion HYL can play a therapeutic role in CB treatment by regulating serum metabolites to modulate the core target genes related to inflammation,reducing inflammation level and alleviating metabolic disorders in the body.
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