Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk

Hui Yang,1 Wei Sun,2 Pei Ma,1 Chunsuo Yao,1 Yannan Fan,1 Shuyi Li,1 Jiqiao Yuan,1 Ziqian Zhang,1 Xuyu Li,1 Mingbao Lin,1 Qi Hou1 1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union M...

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Autores principales:	Yang H, Sun W, Ma P, Yao C, Fan Y, Li S, Yuan J, Zhang Z, Li X, Lin M, Hou Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	allergic airway inflammation multi-component ple syk synergistic effect Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/71fedd6e4285444485a188390fc244b6
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spelling	oai:doaj.org-article:71fedd6e4285444485a188390fc244b62021-12-02T13:40:27ZMultiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk1178-7031https://doaj.org/article/71fedd6e4285444485a188390fc244b62020-11-01T00:00:00Zhttps://www.dovepress.com/multiple-components-rapidly-screened-from-perilla-leaves-attenuate-ast-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Hui Yang,1 Wei Sun,2 Pei Ma,1 Chunsuo Yao,1 Yannan Fan,1 Shuyi Li,1 Jiqiao Yuan,1 Ziqian Zhang,1 Xuyu Li,1 Mingbao Lin,1 Qi Hou1 1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Mingbao Lin; Qi Hou Tel +86-10-63165192; +86-10-63165191Email mingbaolin@imm.cams.cn; houq@imm.ac.cnBackground: Perilla frutescens (L.) Britt., a classic medicinal plant, has been demonstrated to have anti-inflammatory and anti-allergic effects in asthma. Perilla leaves extract (PLE) exerted significant therapeutic effect against allergic asthma inflammation through Syk inhibition. But the active chemical ingredients from PLE are complex and unclear, it is difficult to fully elucidate its pharmacological mechanisms.Methods: A method was established for rapid screening and characterization of active ingredients from PLE that targeted Syk, with which three potential active ingredients were identified. By using OVA-induced allergic asthma mouse model in vivo, OVA-induced human PBMCs inflammation model and DNP-IgE/BSA-induced RBL-2H3 cells model in vitro, the effects and mechanisms of PLE and its active components were evaluated.Results: Using Syk-affinity screening method, roseoside (RosS), vicenin-2 (Vic-2) and rosmarinic acid (RosA) were identified from PLE. In vitro, PLE and its ingredients showed significant inhibitory activities against Syk, with their mixture (Mix, prepared by RosS, Vic-2 and RosA in accordance with their ratio in Syk-conjugated beads bound fraction) showing a stronger inhibitory activity. RosS, Vic-2 and RosA also showed significant effects on allergic asthma, and a synergistic effect of Mix was observed. Moreover, treatment with PLE, RosS, Vic-2, RosA, and Mix significantly inhibited the expression and phosphorylation of Syk, PKC, NF-κB p65, and cPLA2 in allergic mice lung tissue and in RBL-2H3 cells.Conclusion: PLE may alleviate allergic airway inflammation partly through the multiple components synergistic targeting on Syk and its downstream inflammatory pathway.Keywords: allergic airway inflammation, multi-component, PLE, Syk, synergistic effectYang HSun WMa PYao CFan YLi SYuan JZhang ZLi XLin MHou QDove Medical Pressarticleallergic airway inflammationmulti-componentplesyksynergistic effectPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 13, Pp 897-911 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	allergic airway inflammation multi-component ple syk synergistic effect Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	allergic airway inflammation multi-component ple syk synergistic effect Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Yang H Sun W Ma P Yao C Fan Y Li S Yuan J Zhang Z Li X Lin M Hou Q Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk
description	Hui Yang,1 Wei Sun,2 Pei Ma,1 Chunsuo Yao,1 Yannan Fan,1 Shuyi Li,1 Jiqiao Yuan,1 Ziqian Zhang,1 Xuyu Li,1 Mingbao Lin,1 Qi Hou1 1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Mingbao Lin; Qi Hou Tel +86-10-63165192; +86-10-63165191Email mingbaolin@imm.cams.cn; houq@imm.ac.cnBackground: Perilla frutescens (L.) Britt., a classic medicinal plant, has been demonstrated to have anti-inflammatory and anti-allergic effects in asthma. Perilla leaves extract (PLE) exerted significant therapeutic effect against allergic asthma inflammation through Syk inhibition. But the active chemical ingredients from PLE are complex and unclear, it is difficult to fully elucidate its pharmacological mechanisms.Methods: A method was established for rapid screening and characterization of active ingredients from PLE that targeted Syk, with which three potential active ingredients were identified. By using OVA-induced allergic asthma mouse model in vivo, OVA-induced human PBMCs inflammation model and DNP-IgE/BSA-induced RBL-2H3 cells model in vitro, the effects and mechanisms of PLE and its active components were evaluated.Results: Using Syk-affinity screening method, roseoside (RosS), vicenin-2 (Vic-2) and rosmarinic acid (RosA) were identified from PLE. In vitro, PLE and its ingredients showed significant inhibitory activities against Syk, with their mixture (Mix, prepared by RosS, Vic-2 and RosA in accordance with their ratio in Syk-conjugated beads bound fraction) showing a stronger inhibitory activity. RosS, Vic-2 and RosA also showed significant effects on allergic asthma, and a synergistic effect of Mix was observed. Moreover, treatment with PLE, RosS, Vic-2, RosA, and Mix significantly inhibited the expression and phosphorylation of Syk, PKC, NF-κB p65, and cPLA2 in allergic mice lung tissue and in RBL-2H3 cells.Conclusion: PLE may alleviate allergic airway inflammation partly through the multiple components synergistic targeting on Syk and its downstream inflammatory pathway.Keywords: allergic airway inflammation, multi-component, PLE, Syk, synergistic effect
format	article
author	Yang H Sun W Ma P Yao C Fan Y Li S Yuan J Zhang Z Li X Lin M Hou Q
author_facet	Yang H Sun W Ma P Yao C Fan Y Li S Yuan J Zhang Z Li X Lin M Hou Q
author_sort	Yang H
title	Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk
title_short	Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk
title_full	Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk
title_fullStr	Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk
title_full_unstemmed	Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk
title_sort	multiple components rapidly screened from perilla leaves attenuate asthma airway inflammation by synergistic targeting on syk
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/71fedd6e4285444485a188390fc244b6
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Multiple Components Rapidly Screened from Perilla Leaves Attenuate Asthma Airway Inflammation by Synergistic Targeting on Syk

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