Planta Med 2014; 80 - PE10
DOI: 10.1055/s-0034-1382574

Investigation of Nelumbo nucifera flower for human opioid receptor displacement affinity

M Kumarihamy 1, F Leon 2, S Pettaway 2, C Hill 1, M Wang 1, M ElSohly 3, SJ Cutler 1, 2, I Muhammad 1
  • 1National Center for Natural Products Research
  • 2Departments of Medicinal Chemistry
  • 3Pharmaceutics, School of Pharmacy, RIPS, University of Mississippi, University, MS 38677, USA

Nelumbo nucifera (Sacred Lotus) is a perennial aquatic medicinal plant widely distributed in Asia. The flowers when smoked or made into a tea are reported to have a calming effect. The EtOH extracts of pink and white flower showed inhibition (54%) of k- opioid receptor. Bioassay guided fractionation of the extract led to the isolation and identification of eight benzyltetrahydroisoquinolines, namely, nuciferine, N-nor-nuciferine, neferine, asimilobine, armepavine, O-methylcoclaurine, N-methylcoclaurine, and coclaurine. Among them, N- and O-methylcoclaurine, and coclaurine showed considerable affinities for k-opioid (Ki 0.92±0.004, 3.46±0.30, 2.20±0.16 µM and IC50's 1.85, 6.92, 4.39 µM) receptors. In contrast, neferine displayed significant binding affinities for δ- and µ-opioid receptors (Ki 0.757±0.114 and 1.767± 0.201 µM, respectively). UHPLC/MS analysis revealed that these alkaloids are chemical and bioactive markers of pink and white flowers displaying opioid binding affinities. Based on the GTPγS functional agonist assay, neferine is determined as a weak δ- agonist.

Acknowledgement: This work was supported by NIH-National Institute of General Medical Sciences grant number P20GM104932.