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

Authors Zhang, Yan; Wang, Chaoran; Guo, Zhimou; Zhang, Xiuli; Wang, Zhiwei; Liang, Xinmiao; Civelli, Olivier

Journal JOURNAL OF ETHNOPHARMACOLOGY , SEP 29 2014,3:155

DOI 10.1016/j.jep.2014.07.057 PubMed 25107388

Abstract Ethnopharmacological relevance: The need for an efficacious analgesic without unwanted side effects is urgent. kappa-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 kappa-opioid receptor as the target to identify the active components from traditional Chinese medicines (TCMs).Materials and methods: The kappa-opioid receptor was expressed in human embryonic kidney-293 T cells (HEK293T). Fluorometric Imaging Plate Reader (FLIPR) assay was used for the determination of Ca2+ response when kappa-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 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 kappa-opioid receptor ligands. The strategy that we adopted can be applied to other naturally-occurring active alkaloids acting at different receptors. (C) 2014 Published by Elsevier Ireland Ltd.

Species covered 延胡索 Corydalis yanhusuo