Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.

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 s...

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Autores principales:	Kedi Liu, Xingru Tao, Jing Su, Fei Li, Fei Mu, Shi Zhao, Xinming Lu, Jing Li, Sha Chen, Taiwei Dong, Jialin Duan, Peifeng Wei, Miaomiao Xi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/efe2123a54dd45fbbcbc14bb2737ca06
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spelling	oai:doaj.org-article:efe2123a54dd45fbbcbc14bb2737ca062021-12-02T20:07:58ZNetwork pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.1932-620310.1371/journal.pone.0255736https://doaj.org/article/efe2123a54dd45fbbcbc14bb2737ca062021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255736https://doaj.org/toc/1932-6203Dalbergia 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.Kedi LiuXingru TaoJing SuFei LiFei MuShi ZhaoXinming LuJing LiSha ChenTaiwei DongJialin DuanPeifeng WeiMiaomiao XiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0255736 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kedi Liu Xingru Tao Jing Su Fei Li Fei Mu Shi Zhao Xinming Lu Jing Li Sha Chen Taiwei Dong Jialin Duan Peifeng Wei Miaomiao Xi Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.
description	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.
format	article
author	Kedi Liu Xingru Tao Jing Su Fei Li Fei Mu Shi Zhao Xinming Lu Jing Li Sha Chen Taiwei Dong Jialin Duan Peifeng Wei Miaomiao Xi
author_facet	Kedi Liu Xingru Tao Jing Su Fei Li Fei Mu Shi Zhao Xinming Lu Jing Li Sha Chen Taiwei Dong Jialin Duan Peifeng Wei Miaomiao Xi
author_sort	Kedi Liu
title	Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.
title_short	Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.
title_full	Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.
title_fullStr	Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.
title_full_unstemmed	Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.
title_sort	network pharmacology and molecular docking reveal the effective substances and active mechanisms of dalbergia odoriferain protecting against ischemic stroke.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/efe2123a54dd45fbbcbc14bb2737ca06
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Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.

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