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从紫苏叶中快速筛选出的多种成分通过协同靶向脾酪氨酸激酶减轻哮喘气道炎症。

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

作者信息

Yang Hui, Sun Wei, Ma Pei, Yao Chunsuo, Fan Yannan, Li Shuyi, Yuan Jiqiao, Zhang Ziqian, Li Xuyu, Lin Mingbao, Hou Qi

机构信息

State 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.

Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.

出版信息

J Inflamm Res. 2020 Nov 13;13:897-911. doi: 10.2147/JIR.S281393. eCollection 2020.

DOI:10.2147/JIR.S281393
PMID:33223845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7671475/
Abstract

BACKGROUND

(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 cPLA 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.

摘要

背景

紫苏（L.）Britt. 是一种经典的药用植物，已被证明在哮喘中具有抗炎和抗过敏作用。紫苏叶提取物（PLE）通过抑制脾酪氨酸激酶（Syk）对过敏性哮喘炎症发挥显著治疗作用。但PLE中的活性化学成分复杂且不明确，难以充分阐明其药理机制。

方法

建立了一种快速筛选和鉴定PLE中靶向Syk的活性成分的方法，借此鉴定出三种潜在活性成分。通过体内卵清蛋白（OVA）诱导的过敏性哮喘小鼠模型、体外OVA诱导的人外周血单个核细胞（PBMCs）炎症模型以及二硝基苯基 - 免疫球蛋白E（DNP-IgE）/牛血清白蛋白（BSA）诱导的大鼠嗜碱性粒细胞白血病（RBL-2H3）细胞模型，评估PLE及其活性成分的作用和机制。

结果

采用Syk亲和筛选法从PLE中鉴定出玫瑰糖苷（RosS）、异荭草苷（Vic-2）和迷迭香酸（RosA）。在体外，PLE及其成分对Syk表现出显著抑制活性，其混合物（Mix，由RosS、Vic-2和RosA按照它们在与Syk结合的珠子结合部分中的比例制备）表现出更强的抑制活性。RosS、Vic-2和RosA对过敏性哮喘也有显著作用，且观察到Mix具有协同效应。此外，用PLE、RosS、Vic-2、RosA和Mix处理可显著抑制过敏性小鼠肺组织和RBL-2H3细胞中Syk、蛋白激酶C（PKC）、核因子κB p65（NF-κB p65）和胞浆型磷脂酶A2（cPLA）的表达和磷酸化。

结论

PLE可能通过多种成分协同靶向Syk及其下游炎症途径部分缓解过敏性气道炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/dc7b392d4311/JIR-13-897-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/6694f490679f/JIR-13-897-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/eabecfd25c08/JIR-13-897-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/a03af54faf36/JIR-13-897-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/c55a595c434e/JIR-13-897-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/cf84266bb388/JIR-13-897-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/0ed155e61394/JIR-13-897-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/dc7b392d4311/JIR-13-897-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/6694f490679f/JIR-13-897-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/eabecfd25c08/JIR-13-897-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/a03af54faf36/JIR-13-897-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/c55a595c434e/JIR-13-897-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/cf84266bb388/JIR-13-897-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/0ed155e61394/JIR-13-897-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c848/7671475/dc7b392d4311/JIR-13-897-g0007.jpg

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