Recently, the number of patients diagnosed with dementia has increased. The World Health Organization (WHO) estimates that 50 million patients suffer from dementia. Although several therapeutic strategies have been proposed, currently, there is no curative approach for treating dementia. Neurodegeneration is an irreversible process. As this disease gradually progresses over 15–20 years, a low-cost and sustainable method for preventing these diseases is desired. Cacao nib is consumed in many countries, and a recent clinical study indicated that cocoa intake upregulates brain-derived neurotrophic factor (BDNF), which plays a significant role in memory formation and neuronal cell survival. In the present study, neural cells were treated with cacao nib extract or the 17 characteristic components of cacao nib. Treatment with Cacao nib extract upregulates BDNF mRNA expression. In addition, cacao nib extract elicits the phosphorylation of cAMP-response-element-binding protein (CREB), which regulates the transcription of BDNF. Among the 17 species screened, isovaleraldehyde (IVA), also known as an aroma component of cacao nibs extract, improved BDNF mRNA expression without SH-SY5Y cell toxicity. IVA also promoted CREB phosphorylation through a cAMP-dependent protein kinase (PKA)-dependent mechanism. In conclusion, IVA could be responsible for the BDNF upregulation effect of cacao nib, and IVA upregulated BDNF expression via the PKA–CREB axis.

最近，被诊断患有痴呆症的患者数量有所增加。世界卫生组织 (WHO) 估计有 5000 万患者患有痴呆症。尽管已经提出了几种治疗策略，但目前还没有治疗痴呆的方法。神经退行性变是一个不可逆转的过程。随着这种疾病在 15-20 年内逐渐进展，人们需要一种低成本且可持续的方法来预防这些疾病。许多国家都消费可可粒，最近的一项临床研究表明，可可摄入量会上调脑源性神经营养因子 (BDNF)，而脑源性神经营养因子在记忆形成和神经细胞存活中发挥着重要作用。在本研究中，神经细胞用可可粒提取物或可可粒的 17 种特征成分进行处理。可可粒提取物处理可上调 BDNF mRNA 表达。此外，可可粒提取物还可引发 cAMP 响应元件结合蛋白 (CREB) 的磷酸化，从而调节 BDNF 的转录。在筛选的 17 个物种中，异戊醛 (IVA)（也称为可可粒提取物的香气成分）可改善 BDNF mRNA 表达，且无 SH-SY5Y 细胞毒性。IVA 还通过 cAMP 依赖性蛋白激酶 (PKA) 依赖性机制促进 CREB ​​磷酸化。总之，IVA 可能是可可粒上调 BDNF 作用的原因，并且 IVA 通过 PKA-CREB ​​轴上调 BDNF 表达。