Background Huntington Disease (HD) has traditionally been described as a disorder purely of the brain, however emerging evidence indicates that peripheral abnormalities are also commonly seen. Among others, unintended body weight loss represents a hallmark of peripheral HD pathology. It correlates with disease progression and significantly affects the quality of life of HD patients. Although the underlying molecular mechanism is still unknown, evidence suggests that body weight loss seems not to be secondary to inadequate nutrition or to chorea, but rather attributable to changes in the metabolism and defective nutrients absorption along the intestinal tract. Curcumin, a naturally occurring polyphenol, has been validated to exert important beneficial effects in a multitude of gastrointestinal dysfunction and neurodegenerative processes similar to those occurring in HD. Although its therapeutic effect in HD is still questionable, recent evidence indicates that curcumin significantly improves neuropathology as well neurochemical and neurobehavioral defects in a mouse model of the disease, however whether it may be suited to be developed to treat gastrointestinal dysfunction in the disease is not clear yet.
Aim In this study, we aimed to investigate the potential beneficial effects that the chronic administration of curcumin may have on gastrointestinal dysfunction commonly occurring in R6/2 mice as the disease progresses.
Method Curcumin along with bioperine (bioavailability enhancing-agent) was orally administered to females 10 days before pregnancy and during the entire gestation period up to the end of lactation. Starting from the third week of age, pups were daily treated with 40 mg/kg curcumin for 7 weeks. KCl-induced contraction was evaluated in isolated intestinal tract from both curcumin and vehicle-treated mice.
Results Our preliminary data demonstrate that chronic administration of curcumin is safe and well tolerated in R6/2 mice. It prevents the gradual weight loss despite no changes in food intake were observed. From the functional point of view, curcumin considerably ameliorates the intestinal phenotype and restores the normal intestinal reactivity compared to untreated R6/2 mice.
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