Dataset Information

Deciphering Pharmacological Mechanism of Buyang Huanwu Decoction for Spinal Cord Injury by Network Pharmacology Approach.

ABSTRACT:

Objective

The purpose of this study was to investigate the mechanism of action of the Chinese herbal formula Buyang Huanwu Decoction (BYHWD), which is commonly used to treat nerve injuries, in the treatment of spinal cord injury (SCI) using a network pharmacology method.

Methods

BYHWD-related targets were obtained by mining the TCMSP and BATMAN-TCM databases, and SCI-related targets were obtained by mining the DisGeNET, TTD, CTD, GeneCards, and MalaCards databases. The overlapping targets of the abovementioned targets may be potential therapeutic targets for BYHWD anti-SCI. Subsequently, we performed protein-protein interaction (PPI) analysis, screened the hub genes using Cytoscape software, performed Gene Ontology (GO) annotation and KEGG pathway enrichment analysis, and finally achieved molecular docking between the hub proteins and key active compounds.

Results

The 189 potential therapeutic targets for BYHWD anti-SCI were overlapping targets of 744 BYHWD-related targets and 923 SCI-related targets. The top 10 genes obtained subsequently included AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN. Fifteen signaling pathways were also screened out after enrichment analysis and literature search. The results of molecular docking of key active compounds and hub target proteins showed a good binding affinity for both.

Conclusion

This study shows that BYHWD anti-SCI is characterized by a multicomponent, multitarget, and multipathway synergy and provides new insights to explore the specific mechanisms of BYHWD against SCI.

SUBMITTER: Xiong Z

PROVIDER: S-EPMC8087484 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Buyang Huanwu Decoction (BYHWD) is used to promote blood circulation and is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used to treat ischemic stroke are not well understood. The current study aimed to identify the potential active components of BYHWD and explore its mechanism using network pharmacology and bioinformatics analyses. The compounds of BYHWD were obtained from public databases. Oral bioavailability and drug-likeness were screened using the absorption, distribution, metabolism and excretion (ADME) criteria. Components of BYHWD, alongside the candidate targets of each component and the known therapeutic targets of ischemic stroke were collected. A network of target gene compounds and cerebral ischemia compounds was established using network pharmacology data sources. The enrichment of key targets and pathways was analyzed using STRING and DAVID databases. Moreover, three of key targets [IL6, VEGFA and hypoxia-inducible-factor-1α (HIF-1α)] were verified using western blot analysis. Network analysis determined 102 compounds in seven herbal medicines that were subjected to ADME screening. A total of 42 compounds as well as 79 genes formed the principal pathways associated with ischemic stroke. The 16 key compounds identified were baicalein, beta-carotene, baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, bifendate, formononetin, calycosin, astragaloside IV, stigmasterol, sitosterol, Z-ligustilide, and dihydrocapsaicin. The core genes in this network were IL6, TNF, VEGFA, HIF-1α, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. Furthermore, the TNF, IL17, apoptosis, PI3K-Akt, toll-like receptor, MAPK, NF-κB and HIF-1 signaling pathways were identified to be associated with ischemic stroke. Compared with the control group (no treatment), BYHWD significantly inhibited the expression of IL6 and increase the expression of HIF-1α and VEGFA. Network pharmacology analyses can help to reveal close interactions between multi-components and multi-targets and enhance understanding of the potential effects of BYHWD on ischemic stroke.