Water-soluble Derivative Of Propolis Mitigates Learning And Memory Impairment In Mice And Effects And Mechanisms Of Intracerebroventricular Administration Of Human Opiorphin

This paper contains two sections and the first section was focused on the effect of water-soluble derivative of propolis(WSDP)on learning and memory of mice.It has been reported that propolis possessed a broad spectrum of biological activities but including few studies on learning and memory by now.Thus,this study was aimed to investigate the effect of WSDP on scopolamine-induced learning and memory impairment in mice.The WSDP was prepared from fresh Chinese propolis and its major constituents were identified by high performance liquid chromatography(HPLC)analysis. WSDP(50 mg/kg,100 mg/kg)was given by intragastric administration(i.g.)40 min prior to the intraperitoneal(i.p.)injection of scopolamine(1 mg/kg).The effect on amnesia was investigated with both hidden-platform acquisition training and probe trial testing in Morris water maze test.The results from 100 mg/kg WSDP group showed significant mitigation scopolamine-induced amnesia in mice.Furthermore,WSDP's effect on the acetylcholinesterase(ACHE)activity in the cerebral cortex and hippocampus was also assayed.As a result,WSDP(100 mg/kg)significantly inhibited AChE activity in the hippocampus of scopolamine-treated mice.These results indicated that WSDP may mitigate amnesia in vivo through inhibition of AChE activity in the hippocampus,which suggested propolis may have potential as a pharmaceutical of brain protection with elderly population for preventing Alzheimer's disease(AD)and other neurodegenerative diseases.In the second section we studied the antinociceptive effects and mechanisms of intracerebroventricular(i.c.v.)administration of human Opiorphin.Opiorphin is a QRFSR pentapeptide.Intracerebroventricular(i.c.v.)administration of Opiorphin(1.25, 2.5,5,10μg/kg body weight)dose- and time-related induced potent analgesic effect (ED50 = 3.22μg/kg)in tail immersion test.The effect of Opiorphin(5μg/kg,i.c.v.)on the analgesic behaviors in tail immersion test was fully blocked by the broad-spectrum opioid antagonist naloxone(2 mg/kg,s.c given 10 min before the test).When Opiorphin (5μg/kg)co-injected(i.c.v.)with selectiveμ- opioid receptor antagonist beta-funaltrexamine andδ- opioid receptor antagonist naltrindole(12 nmol/mouse, respectively),the antinociceptive effect exerted by Opiorphin was partly blocked. However,co-injected(i.c.v.)with the selectiveκ- opioid receptor antagonist nor-binaltorphimine(12 nmol/mouse)did not significantly affect the antinociceptive response produced by Opiorphin.These findings suggested that Opiorphin might play an important role in pain modulation at supraspinal level in mice and these effects were achieved by activating endogenous opioid-dependent pathways,involvingμ- andδ-opioid receptors.Opiorphin may have potential as novel therapeutic compounds for the treatment of pain.