In vitro opioid receptor displacement affinity and in vitro behavioral studies by tetrad assay of Nelumbo nucifera flower

Nelumbo nucifera Geartn. (lotus), is a perennial aquatic plant native to South-East Asia. Both white and pink flowers are reported to have a calming effect when smoked or made into a tea. Bioassay-guided isolation and identification of from EtOH extracts revealed eight benzyltetrahydroisoquinoline alkaloids, nuciferine (1), N-nor-nuciferine (2), asimilobine (3), armepavine (4), O-methylcoclaurine (5), N-methylcoclaurine (6), coclaurine (7), and neferine (8), and as well as linoleic and palmitic acids. Compounds 5 – 8 showed high percent of radioligand displacement in opioid receptors displayed various degrees of displacement activities. Based on the GTPγS functional agonist assay, neferine was determined to be a weak δ-agonist. The acidic and basic partitions, 1, 7 and mixture of 5 – 7 were subjected to mouse tetrad assay, of which the acidic partition displayed decreased locomotion, and increased catalepsy, hypothermia, and antinociceptive activity at doses of 75 – 100 mg/kg/ip. This work, along with traditional use and the reported bioactivities of the alkaloids, suggested further studies on N. nucifera are needed to understand the roles that the extracts or individual compounds might contribute to the behavioral effects. Acknowledgement: Supported by the National Institute of General Medical Sciences (NIGMS), NIH Grant Number P20GM104932, and COBRE, CORE-NPN, Research Core C.