Water composed of reduced hydrogen bonds activated by localized surface plasmon resonance effectively enhances anti-viral and anti-oxidative activities of melatonin

•PAW significantly increases the solubility of melatonin that endows lipophilic property.•Melatonin dissolved in PAW displays greater anti-viral activity against dengue infection.•PAW plays synergetic effects with melatonin to raise melatonin's anti-oxidative function.•Melatonin dissolved in PAW greatly improves hepatic bioenergetics after sleep deprivation.•PAW may act as a powerful medium to greatly enhance melatonin’s therapeutic efficiency. Melatonin is a lipophilic antioxidant generally dissolved in organic solvent before delivery. However, the presence of organics may severely depress the functional effects of melatonin. By rendering deionized water (DIW) flow through gold nano-particles under localized surface plasmon resonant illumination, we developed plasmon-activated water (PAW) which successfully increases the solubility of melatonin to 150.325%. Melatonin dissolved in PAW also exhibits stronger anti-viral and anti-oxidative activities than that dissolved in DIW in which the percentage of dengue virus infected human hepatocellular carcinoma cells is remarkably decreased (14.7% vs. 20.6%) whilst the clearance rate of hydroxyl radical is significantly enhanced (11.9% vs. 6.69%), respectively. Moreover, in vivo approaches further show that following chronic sleep deprivation, the level of oxidative stress, hepatic bioenergetics, anti-oxidative enzyme activity, and metabolic function are all significantly improved in rats received melatonin prepared in PAW than that in DIW. As the bio-activity of melatonin depends largely on its solubility, utilizing PAW as a non-organic solvent will not only enhance the anti-viral and anti-oxidative function of melatonin, but also offer great potential for clinical use of melatonin as a therapeutic strategy to depress virus infection and counteract oxidative damage in a more natural, more economic and more efficient way.