Combining Lycopene, Quercetin, and Poloxamer 188 Therapy Reduces Learning and Memory Deficits in the 3-nitropropionic Acid-induced Rat Model of Huntington's Disease.

INTRODUCTION: The current study was carried out to assess the pharmacological action of combine effect of Poloxamer 188, Lycopene, and Quercetin on memory and energy deficit in Huntington's disease-like signs induced by 3 Nitropropionic acid in Wistar rats. METHODS: After one week of acclimatization all animals were randomly assigned in six groups, (n = 6), as normal control, Huntington's disease control, Lycopene treated (25 mg/kg po), Quercetin treated (50 mg/kg po), combinations with and without Poloxamer 188 (80 mg/kg po) with adjunct administration of 3 nitropropionic acid (10 mg/kg i.p.) except in normal control. Memory and energy deficits were induced by i.p. administration of 3 Nitropropionic acid (10 mg/kg) for 14 days. A novel object recognition test was assessed on the 14th and 15th days of the experiment, post-treatment, and other biochemical parameters were examined at the end of the experiment. RESULT: The results showed that the 3-nitropropionic acid administration for 14 days produced memory and energy deficits in rats. Moreover, the combination of Lycopene and Quercetin, with and without Poloxamer 188, showed significant effects on memory enhancement, energy deficit, and body weight compared to single-drug therapy. However, the combination did not produce a significant increase in brain weight compared to single-drug therapy. Moreover, the combination also showed remarkable enhancement in Succinate dehydrogenase activity and reduction in Lactate dehydrogenase activity compared to monotherapy. DISCUSSION: The combined therapy of lycopene, quercetin, and poloxamer 188 significantly improved 3-nitropropionic acid-induced cognitive deficits by reducing oxidative stress and enhancing cholinergic function. This synergistic effect also normalized key mitochondrial enzymes, suggesting strong neuroprotective potential against Huntington's disease progression. CONCLUSION: Administration of 3-nitropropionic acid for 14 days produces memory and energy deficits in rats. Combining the effects of Lycopene and Quercetin, with or without Poloxamer 188, enhances memory and reduces energy deficit more effectively than mono-therapy. This study assessed the effects of combined lycopene, quercetin, and poloxamer 188 treatment on cognition and energy deficits in a 3-nitropropionic acid-induced rat model. Treating with a combination of the three compounds resulted in behavioral and biochemical improvements compared to the disease control group. There may be a tendency for the combined treatments to have additive effects on the subjects compared to individual treatments. However, the results of this study should be interpreted with caution.