Dimerization of Resveratrol Induced by Red Light and Its Synergistic Analgesic Effects with Cobra Neurotoxin

Abstract

Resveratrol polymer has better effects than monomer in some aspects as reported, but most of synthetic methods acquire severe conditions and no analgesic effects are investigated. A novel method is found to synthesize resveratrol polymer by excitation of photosensitizer pheophorbide at red light of 630 nm. The polymer was analyzed by fluorescence spectra and HPLC, further isolated by preparative liquid chromatography and identified as a resveratrol dimer by MS and NMR. Analgesic effects were measured by acetic acid writhing and hot-plate test in mice. The resveratrol dimer has the stronger analgesic effects than monomer, and drug combination of the dimer and cobra neurotoxin enhances and prolongs analgesic effects, suggesting the synergistic action. Simulation of molecular interaction reveals that the dimer spontaneously binds to cobra neurotoxin and makes a complex substance. The dimer can interact with cyclooxygenase-2, μ receptor and nicotine receptor, the synergistic analgesic effects of the complex are attributed to its multiple targets role. The combination of resveratrol dimer and cobra neurotoxin may make up for their deficiencies in analgesic effects, and has prospects in clinical use.