In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 9 ( 2021-9-28), p. e0255736-
Abstract:
Dalbergia Odorifera (DO) has been widely used for the treatment of cardiovascular and cerebrovascular diseasesinclinical. However, the effective substances and possible mechanisms of DO are still unclear. In this study, network pharmacology and molecular docking were used toelucidate the effective substances and active mechanisms of DO in treating ischemic stroke (IS). 544 DO-related targets from 29 bioactive components and 344 IS-related targets were collected, among them, 71 overlapping common targets were got. Enrichment analysis showed that 12 components were the possible bioactive components in DO, which regulating 9 important signaling pathways in 3 biological processes including ‘oxidative stress’ (KEGG:04151, KEGG:04068, KEGG:04915), ‘inflammatory response’(KEGG:04668, KEGG:04064) and ‘vascular endothelial function regulation’(KEGG:04066, KEGG:04370). Among these, 5 bioactive components with degree≥20 among the 12 potential bioactive components were selected to be docked with the top5 core targets using AutodockVina software. According to the results of molecular docking, the binding sites of core target protein AKT1 and MOL002974, MOL002975, and MOL002914 were 9, 8, and 6, respectively, and they contained 2, 1, and 0 threonine residues, respectively. And some binding sites were consistent, which may be the reason for the similarities and differences between the docking results of the 3 core bioactive components. The results of in vitro experiments showed that OGD/R could inhibit cell survival and AKT phosphorylation which were reversed by the 3 core bioactive components. Among them, MOL002974 (butein) had a slightly better effect. Therefore, the protective effect of MOL002974 (butein) against cerebral ischemia was further evaluated in a rat model of middle cerebral artery occlusion (MCAO) by detecting neurological score, cerebral infarction volume and lactate dehydrogenase (LDH) level. The results indicated that MOL002974 (butein) could significantly improve the neurological score of rats, decrease cerebral infarction volume, and inhibit the level of LDH in the cerebral tissue and serum in a dose-dependent manner. In conclusion, network pharmacology and molecular docking predicate the possible effective substances and mechanisms of DO in treating IS. And the results are verified by the in vitro and in vivo experiments. This research reveals the possible effective substances from DO and its active mechanisms for treating IS and provides a new direction for the secondary development of DO for treating IS.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0255736
DOI:
10.1371/journal.pone.0255736.g001
DOI:
10.1371/journal.pone.0255736.g002
DOI:
10.1371/journal.pone.0255736.g003
DOI:
10.1371/journal.pone.0255736.g004
DOI:
10.1371/journal.pone.0255736.g005
DOI:
10.1371/journal.pone.0255736.g006
DOI:
10.1371/journal.pone.0255736.g007
DOI:
10.1371/journal.pone.0255736.g008
DOI:
10.1371/journal.pone.0255736.g009
DOI:
10.1371/journal.pone.0255736.g010
DOI:
10.1371/journal.pone.0255736.g011
DOI:
10.1371/journal.pone.0255736.g012
DOI:
10.1371/journal.pone.0255736.g013
DOI:
10.1371/journal.pone.0255736.g014
DOI:
10.1371/journal.pone.0255736.g015
DOI:
10.1371/journal.pone.0255736.t001
DOI:
10.1371/journal.pone.0255736.t002
DOI:
10.1371/journal.pone.0255736.t003
DOI:
10.1371/journal.pone.0255736.s001
DOI:
10.1371/journal.pone.0255736.s002
DOI:
10.1371/journal.pone.0255736.s003
DOI:
10.1371/journal.pone.0255736.r001
DOI:
10.1371/journal.pone.0255736.r002
DOI:
10.1371/journal.pone.0255736.r003
DOI:
10.1371/journal.pone.0255736.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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