クルクミン誘導体CUD003の慢性前投与は過剰な炎症を抑制することによりLPS誘発抑うつ行動を予防する

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  • Repeated prophylactic treatment of a curcumin derivative CUD003 prevents lipopolysaccharide-induced depressive-like behavior by inhibiting excessive inflammation in mice.

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<p>Previously, we revealed that repeated prophylactic treatment with CUD003, a synthetic derivate of curcumin, suppressed the development of depressive-like behavior at lower doses than curcumin in a lipopolysaccharide (LPS)-induced depression model. In this study, we investigated the possible mechanism of the preventive effect of CUD003 on the LPS-induced depression-like behaviors in mice. Male BALB/c mice were orally pretreated with curcumin or CUD003 for 5 days before receiving single intraperitoneal injection of LPS (0.5 mg/kg). Plasma interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were assessed by enzyme-linked immunosorbent assay. Furthermore, reactive oxygen species (ROS) level in the hippocampal CA1 region was assessed by dihydroethidium staining. Twenty-four hours after LPS administration, IL-1β and TNF-α levels in plasma increased. In addition, enhanced oxidative stress with elevated level of ROS was detected in the hippocampus. Pretreatment with CUD003 (3 or 10 mg/kg) and 10 mg/kg curcumin but not 3 mg/kg curcumin suppressed all these changes. These results suggest that the mechanism of preventive effect of CUD003 on the LPS-induced depressive-like behavior in mice is related to suppression of inflammatory cytokines and reduction of oxidative stress.</p>

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