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Journal of Natural Medicines

, Volume 72, Issue 2, pp 582–587 | Cite as

Allergy-preventive effects of linarinic acid and its tetrahydropyrrolo[2,1-b]quinazoline derivatives isolated from Linaria vulgaris

  • Chao Ma
  • Naoko Higashi
  • Kyoko Ishiguro
  • Ying Zhao
  • Linkui Zhang
  • Chenwen Zhao
  • Maosheng Cheng
  • Hisae OkuEmail author
Note

Abstract

Linarinic acid, (−)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid (4a), was isolated from the ethanol extract of Linaria vulgaris Mill. In our previous study, a series of tetrahydropyrrolo[2,1-b]quinazoline derivatives 4b, 4c, 5a, 5b, 6a and 6b that were structurally related to 4a and evaluated as neuroprotective agents were synthesized. The aim of the present study was to investigate the novel features of these compounds. We examined their allergy-preventive effects using an in vivo assay system we developed previously, that monitors a decrease in blood flow in the tail vein of mice subjected to sensitization with hen egg-white lysozyme. We observed that 4a and its three derivatives, amide (6a), ester (5a), bromine (4b), and alcohol substituent (6b), showed significant allergy-preventive activities. The study confirmed the allergy-preventive activity of tetrahydropyrrolo[2,1-b]quinazoline derivatives by comprehensively monitoring the specific blood flow decrease occurring in the induction phase of allergy. This finding may aid in the development of new agents for the treatment of allergic diseases such as atopic dermatitis, allergic asthma, and hay fever.

Keywords

Linaria vulgaris Tetrahydropyrrolo[2,1-b]quinazoline Allergy-preventive activity Hen egg-white lysozyme Linarinic acid Blood flow 

Notes

Acknowledgements

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (Grant 81502931), Fund for Career Development Support Plan for Young and Middle Aged Teachers in Shenyang Pharmaceutical University (Grant ZQN2015024), Student’s Platform for Innovation and Entrepreneurship Training Program (Grant 201710163000175), Program for Innovative Research Team of the Ministry of Education, and Program for Liaoning Innovative Research Team in University. The work was supported in part by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

Compliance with ethical stanadrds

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

11418_2018_1187_MOESM1_ESM.doc (14.3 mb)
Supplementary material 1 The online version of this article contains supplementary materials (DOC 14624 kb)

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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Chao Ma
    • 1
  • Naoko Higashi
    • 2
  • Kyoko Ishiguro
    • 2
  • Ying Zhao
    • 1
  • Linkui Zhang
    • 1
  • Chenwen Zhao
    • 1
  • Maosheng Cheng
    • 1
  • Hisae Oku
    • 2
    Email author
  1. 1.Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, School of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyangChina
  2. 2.School of Pharmacy and Pharmaceutical SciencesMukogawa Women’s UniversityNishinomiyaJapan

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