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<p>Curcumin (Cur) is a bioactive compound with neuroprotective and anti-inflammatory effects, though its clinical application is limited by poor bioavailability. This study assessed the impact of nanocapsulated curcumin (NcCur), formulated Eudragit (EUD) polymer, in a sporadic Alzheimer’s disease (AD) mouse model induced by intracerebroventricular streptozotocin (STZ), with attention to sex-specific differences. Mice received STZ (3 nmol/3 µL) or 0.9% saline on days 1 and 3, followed by intragastric treatment with Cur or NcCur (10&#xa0;mg/kg, on alternate days) from day 22 until euthanasia - a dose previously shown to be effective in behavioral and biochemical modulation in rodent models of neurodegeneration. Behavioral assessments included open field, elevated plus maze (EPM), tail suspension (TST), object recognition, Y-maze, and step-down avoidance tasks (SDAT), performed before and after treatment. After euthanasia, thymus, spleen and adrenal glands were weighed; biochemical assays evaluated oxidative stress, monoaminergic and cholinergic enzymes, and Na⁺K⁺-ATPase activity. NcCur improved short- and long-term memory in both sexes, with greater effects in females (42% and 35%) than males (28% and 25%). In the EPM, NcCur increased open arm time more prominently in females (40%) than males (25%), while TST immobility time was reduced similarly in both. Spatial and aversive memory improved in both sexes, but females showed greater performance in the SDAT. Biochemical analyses showed reductions in reactive species in males (45%) and females (55%) with NcCur; Na⁺K⁺-ATPase activity increased in females (60%) and males (50%). AChE activity was restored in both sexes. NcCur reduced MAO-A/B activities more in females (65%/55%) than in males (45%/35%). Thymus and spleen weights were normalized in both sexes, with stronger effects in females. NcCur also mitigated alterations in thymus and spleen relative weights, suggesting immunomodulatory effects. Some biochemical and behavioral responses were more prominent in females, both sexes benefited from treatments. These findings suggest that NcCur enhances Cur therapeutic potential through multimodal actions linked involving modulation of oxidative stress, cholinergic and monoaminergic systems, and immune-related parameters. NcCur emerges as a promising candidate for AD-like intervention in both sexes.</p> Graphical abstract <p>Summary of the neuroprotective effects of curcumin formulations in a sporadic Alzheimer’s disease model. This figure highlights the multifaceted actions of free curcumin (Cur) and nanocapsule-loaded curcumin (NcCur) in mitigating Alzheimer ’s-related pathologies. The treatments improved anxiety-like behaviors, working memory, and aversive memory while modulating enzymatic pathways, including inhibition of acetylcholinesterase (AChE) and differential regulation of monoamine oxidase (MAO-A and MAO-B) activities. Additionally, they reduced reactive oxygen species (ROS) levels and restored Na+/K+-ATPase pump activity. Female mice showed greater susceptibility to the sporadic Alzheimer STZ model and a stronger response to treatments. These results suggest Cur formulations as promising multitarget therapeutics for AD, enhancing behavioral, synaptic, and cellular functions.</p> <p></p>

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Sex-dependent therapeutic effects of nano-curcumin on alzheimer’s disease: enhanced cognitive and physiological restoration in female mice

  • 期刊论文

  • 发表日期：

    2025年11月24日

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  • Karline da Costa Rodrigues,
  • Meliza da Conceição Oliveira,
  • Isadora Cielo de Souza,
  • Andreza Wachholz Igansi,
  • Ana Vitória Barbosa Lopes,
  • Camila de Oliveira Pacheco,
  • Sandra Elisa Hass,
  • Ricardo Frederico Schumacher,
  • Cristiane Luchese

摘要

Curcumin (Cur) is a bioactive compound with neuroprotective and anti-inflammatory effects, though its clinical application is limited by poor bioavailability. This study assessed the impact of nanocapsulated curcumin (NcCur), formulated Eudragit (EUD) polymer, in a sporadic Alzheimer’s disease (AD) mouse model induced by intracerebroventricular streptozotocin (STZ), with attention to sex-specific differences. Mice received STZ (3 nmol/3 µL) or 0.9% saline on days 1 and 3, followed by intragastric treatment with Cur or NcCur (10 mg/kg, on alternate days) from day 22 until euthanasia - a dose previously shown to be effective in behavioral and biochemical modulation in rodent models of neurodegeneration. Behavioral assessments included open field, elevated plus maze (EPM), tail suspension (TST), object recognition, Y-maze, and step-down avoidance tasks (SDAT), performed before and after treatment. After euthanasia, thymus, spleen and adrenal glands were weighed; biochemical assays evaluated oxidative stress, monoaminergic and cholinergic enzymes, and Na⁺K⁺-ATPase activity. NcCur improved short- and long-term memory in both sexes, with greater effects in females (42% and 35%) than males (28% and 25%). In the EPM, NcCur increased open arm time more prominently in females (40%) than males (25%), while TST immobility time was reduced similarly in both. Spatial and aversive memory improved in both sexes, but females showed greater performance in the SDAT. Biochemical analyses showed reductions in reactive species in males (45%) and females (55%) with NcCur; Na⁺K⁺-ATPase activity increased in females (60%) and males (50%). AChE activity was restored in both sexes. NcCur reduced MAO-A/B activities more in females (65%/55%) than in males (45%/35%). Thymus and spleen weights were normalized in both sexes, with stronger effects in females. NcCur also mitigated alterations in thymus and spleen relative weights, suggesting immunomodulatory effects. Some biochemical and behavioral responses were more prominent in females, both sexes benefited from treatments. These findings suggest that NcCur enhances Cur therapeutic potential through multimodal actions linked involving modulation of oxidative stress, cholinergic and monoaminergic systems, and immune-related parameters. NcCur emerges as a promising candidate for AD-like intervention in both sexes.

Graphical abstract

Summary of the neuroprotective effects of curcumin formulations in a sporadic Alzheimer’s disease model. This figure highlights the multifaceted actions of free curcumin (Cur) and nanocapsule-loaded curcumin (NcCur) in mitigating Alzheimer ’s-related pathologies. The treatments improved anxiety-like behaviors, working memory, and aversive memory while modulating enzymatic pathways, including inhibition of acetylcholinesterase (AChE) and differential regulation of monoamine oxidase (MAO-A and MAO-B) activities. Additionally, they reduced reactive oxygen species (ROS) levels and restored Na+/K+-ATPase pump activity. Female mice showed greater susceptibility to the sporadic Alzheimer STZ model and a stronger response to treatments. These results suggest Cur formulations as promising multitarget therapeutics for AD, enhancing behavioral, synaptic, and cellular functions.