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J Ethnopharmacol. 2014 Sep 29;155(3):1597-602. doi: 10.1016/j.jep.2014.07.057. Epub 2014 Aug 6.

Discovery of N-methyltetrahydroprotoberberines with κ-opioid receptor agonists-opioid receptor agonist activities from corydalis yanhusuo W. T. Wang by using two-dimensional liquid chromatography.

Author information

  • 1Department of Pharmacology, University of California, Irvine, CA 92697, United States.
  • 2Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
  • 3Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: liangxm@dicp.ac.cn.
  • 4Department of Pharmacology, University of California, Irvine, CA 92697, United States; Department of Pharmacological Sciences, University of California, Irvine, CA 92697, United States; Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, United States. Electronic address: ocivelli@uci.edu.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

The need for an efficacious analgesic without unwanted side effects is urgent. κ-opioid receptor agonists are known to exhibit potent analgesic effects and elicited fewer side effects than other opioid agonists. Thus in this study we chose the κ-opioid receptor as the target to identify the active components from traditional Chinese medicines (TCMs).

MATERIALS AND METHODS:

The κ-opioid receptor was expressed in human embryonic kidney-293 T cells (HEK293T). Fluorometric Imaging Plate Reader (FLIPR) assay was used for the determination of Ca(2+) response when κ-opioid receptor was activated. A novel 2D separation system employing C18HCE as the first dimension and a strong cation exchange column (SCX) as the second dimension was conducted for the purification of the active principles.

RESULTS:

With the aid of HPLC-based activity profiling, activities could be linked to two peaks from Corydalis yanhusuo W. T. Wang (C. yanhusuo) extract. Two N-methyltetrahydroprotoberberines with κ-opioid receptor agonist activities were isolated for the first time from C. yanhusuo by using 2D-LC.

CONCLUSIONS:

Our study suggests that N-methyltetrahydroprotoberberines may serve as a new scaffold for κ-opioid receptor ligands. The strategy that we adopted can be applied to other naturally-occurring active alkaloids acting at different receptors.

Copyright © 2014. Published by Elsevier Ireland Ltd.

KEYWORDS:

2D separation; Corydalis yanhusuo W.T. Wang; GPCR; TCMs; κ-opioid receptor

PMID:
25107388
[PubMed - in process]
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