Background: Glutaryl melatonin, which is synthesized from melatonin and is a pineal glandderived
neurohormone with anti-inflammatory and anti-oxidant properties, was comparatively investigated
for its potential use as a topical anti-inflammatory agent.
Objective: Glutaryl melatonin, synthesized and screened for in vitro anti-candidiasis and in vitro and in
vivo anti-inflammatory activities, was formulated as a niosome gel for topical oral evaluation in 5-
fluorouracil-induced oral mucositis in mice.
Methods: In vitro anti-fungal activity in Candida albicans, in vitro anti-inflammatory activity in Escherichia
coli liposaccharide-induced RAW cells and in vivo anti-inflammatory activity using a croton oilinduced
ear edema model in ICR mice were investigated. Mucositis in mice (n= 6/group, 10-week-old
mice) was induced by intraperitoneal injections of 5-fluorouracil, and the mice were subjected to a topical
oral application of niosome gel containing melatonin (2% w/w) or glutaryl melatonin (2% w/w) and were
compared with mice subjected to blank, fluocinolone acetonide (0.5% w/w) and control conditions.
Results: Glutaryl melatonin, at a 14.2 mM concentration, showed the highest fungicidal effect on
C. albicans using the broth dilution method, indicating a nonsignificant difference from 1 μM of nystatin
(p = 0.05). Nitric oxide, interleukin-6 and tumor necrosis factors were analyzed by ELISA.
Liposaccharide-induced RAW cells were significantly reduced by glutaryl melatonin (p < 0.01). Ear
edema inhibition of glutaryl melatonin was significant 1 h after application compared with that of melatonin
(p = 0.03). Food consumption and body weight of the 5-fluorouracil-treated mice were significantly
lower than those of the normal mice before all treatments (p < 0.05). Differences in the amount
of licking behavior, which were observed in the control group for 5 min, were noticeable in the 5-
fluorouracil-treated mice but not in the mice treated with the glutaryl melatonin niosome gel.
Conclusion: Glutaryl melatonin exhibited mild anti-candidiasis and anti-inflammatory properties. The
incorporation of glutaryl melatonin in a niosome gel formulation, demonstrated the potential for topical
oral applications to reduce oral discomfort caused by 5-fluorouracil treatment in mice.