Silva Mariana DE F O DA, Santos-Magnabosco Amanda R, Farias Cláudia Kathariny DA S, Torres Sandra Maria DE, Alves Antônio José, Cadena Pabyton G, Silva Júnior Valdemiro A DA
Universidade Federal Rural de Pernambuco, Departamento de Medicina Veterinária (DMV), Av. Dom Manoel de Medeiros, s/n, Dois Irmãos, 52171-900 Recife, PE, Brazil.
Universidade Federal Rural de Pernambuco, Departamento de Morfologia e Fisiologia Animal (DMFA), Av. Dom Manoel de Medeiros, s/n, Dois Irmãos, 52171-900 Recife, PE, Brazil.
An Acad Bras Cienc. 2025 Feb 7;97(1):e20240607. doi: 10.1590/0001-3765202520240607. eCollection 2025.
The highly lipophilic nature and low aqueous solubility of cannabidiol (CBD) limit its oral bioavailability, resulting in poor intestinal absorption. To overcome these limitations, we proposed the production of a nanoemulsion with CBD to be included in the therapeutic treatment of autism spectrum disorder. The current study aimed to evaluate the effect of CBD-rich corn oil nanoemulsion treatment in male rats born to females exposed to valproic acid (VPA) during pregnancy on autistic-like behaviors and hippocampal histology. Offspring rats were treated orally twice daily with CBD nanoemulsions at different doses (1 and 2 mg/animal). The endpoints evaluated were anxiety, grooming time, exploratory activity, sociability, the social preference index, and hippocampal and cerebral cortex histology. All formulations were characterized as nanoemulsions and showed a reduced vesicle size (107.6 - 72.6 nm), low PDI (0.290-0.432), negative zeta potential (-40.6 mv), and good stability. Prenatal exposure to VPA increased anxiety and grooming time, and reduced exploratory activity, sociability, and the social preference index in the animals. Furthermore, VPA-exposed animals exhibited elevated neuronal death and a reduction in viable cells in the hippocampus. In conclusion, CBD nanoemulsion treatment reversed autistic-like behaviors, potentially by protecting against hippocampal neuronal death. The highly lipophilic nature and low aqueous solubility of cannabidiol (CBD) limit its oral bioavailability, resulting in poor intestinal absorption. To overcome these limitations, we proposed the production of a nanoemulsion with CBD to be included in the therapeutic treatment of autism spectrum disorder. The current study aimed to evaluate the effect of CBD-rich corn oil nanoemulsion treatment in male rats born to females exposed to valproic acid (VPA) during pregnancy on autistic-like behaviors and hippocampal histology. Offspring rats were treated orally twice daily with CBD nanoemulsions at different doses (1 and 2 mg/animal). The endpoints evaluated were anxiety, grooming time, exploratory activity, sociability, the social preference index, and hippocampal and cerebral cortex histology. All formulations were characterized as nanoemulsions and showed a reduced vesicle size (107.6 - 72.6 nm), low PDI (0.290-0.432), negative zeta potential (-40.6 mv), and good stability. Prenatal exposure to VPA increased anxiety and grooming time, and reduced exploratory activity, sociability, and the social preference index in the animals. Furthermore, VPA-exposed animals exhibited elevated neuronal death and a reduction in viable cells in the hippocampus. In conclusion, CBD nanoemulsion treatment reversed autistic-like behaviors, potentially by protecting against hippocampal neuronal death.
大麻二酚（CBD）具有高度亲脂性且水溶性低，这限制了其口服生物利用度，导致肠道吸收不佳。为克服这些限制，我们提议制备含CBD的纳米乳剂，用于自闭症谱系障碍的治疗。本研究旨在评估富含CBD的玉米油纳米乳剂对孕期暴露于丙戊酸（VPA）的雌性所生雄性大鼠的自闭症样行为和海马组织学的影响。对后代大鼠每日口服两次不同剂量（1和2毫克/只）的CBD纳米乳剂。评估的终点指标包括焦虑、梳理时间、探索活动、社交能力、社会偏好指数以及海马和大脑皮层组织学。所有制剂均被表征为纳米乳剂，显示出减小的囊泡尺寸（107.6 - 72.6纳米）、低多分散指数（0.290 - 0.432）、负的zeta电位（-40.6毫伏）以及良好的稳定性。产前暴露于VPA会增加动物的焦虑和梳理时间，并降低探索活动、社交能力和社会偏好指数。此外，暴露于VPA的动物海马中神经元死亡增加且活细胞减少。总之，CBD纳米乳剂治疗可逆转自闭症样行为，可能是通过防止海马神经元死亡实现的。大麻二酚（CBD）具有高度亲脂性且水溶性低，这限制了其口服生物利用度，导致肠道吸收不佳。为克服这些限制，我们提议制备含CBD的纳米乳剂，用于自闭症谱系障碍的治疗。本研究旨在评估富含CBD的玉米油纳米乳剂对孕期暴露于丙戊酸（VPA）的雌性所生雄性大鼠的自闭症样行为和海马组织学的影响。对后代大鼠每日口服两次不同剂量（1和2毫克/只）的CBD纳米乳剂。评估的终点指标包括焦虑、梳理时间、探索活动、社交能力、社会偏好指数以及海马和大脑皮层组织学。所有制剂均被表征为纳米乳剂，并显示出减小的囊泡尺寸（107.6 - 72.6纳米）、低多分散指数（0.290 - 0.432）、负的zeta电位（-40.6毫伏）以及良好的稳定性。产前暴露于VPA会增加动物的焦虑和梳理时间，并降低探索活动、社交能力和社会偏好指数。此外，暴露于VPA的动物海马中神经元死亡增加且活细胞减少。总之，CBD纳米乳剂治疗可逆转自闭症样行为，可能是通过防止海马神经元死亡实现的。
