Co-existence of hypertensive and anti-hypertensive constituents, synephrine, and nobiletin in citrus unshiu peel

Jung Joon Kim, Keunyoung Kim, Ye Ryeon Jung, Yiying Bian, Thien Ngo, Ok Nam Bae, Kyung Min Lim, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


A single herb can contain multiple constituents with diverse bioactivities. We found that the extract of Citrus unshiu peel (CUP), induced abnormal vasoconstriction responses on the freshly isolated rat aortic rings in vitro. CUP stimulated the vasoconstriction alone, and it suppressed the phenylephrine-stimulated vasoconstriction. We studied the reasons behind this abnormal vasoconstriction pattern. Major constituents of CUP were determined and evaluated for their vaso-activities. Notably, synephrine, a contractile agonist, and nobiletin, newly identified to have anti-contractile activity co-existed in CUP. Synephrine and nobiletin competitively blocked or activated the same contractile targets resulting in contradicting and abnormal vasoconstriction responses. Accordingly, the vasoconstriction pattern varies significantly depending on the relative contents of synephrine and nobiletin in CUP. Interestingly, this response pattern could be observed with another plant extract, Acorus gramineus Sol. Collectively, we demonstrated that active ingredients with contradicting bioactivities could co-exist in a single plant extract, interact and produce abnormal response patterns in bioassay, which would give an important insight into the interpretation of unusual activity patterns induced by plant extracts.

Original languageEnglish
Article number1197
Issue number7
StatePublished - 27 Mar 2019

Bibliographical note

Funding Information:
Funding: This work was supported by the National Research Foundation of Korea (NRF) grant (MSIP; No. 2007-0056817 and MSIT; 2018R1A5A2025286) funded by the Korea Government.

Publisher Copyright:
© 2019 by the authors.


  • Bioassay
  • Citrus unshiu
  • Hypertension
  • Nobiletin
  • Synephrine
  • Vasoconstriction


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