Department of Child and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China.
Outpatient Department, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, 150001, China.
J Nutr Biochem. 2024 Jul;129:109638. doi: 10.1016/j.jnutbio.2024.109638. Epub 2024 Apr 5.
Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.
母体妊娠感染是导致后代自闭症谱系障碍(ASD)的一个重要原因,而母体免疫激活(MIA)引起的炎症浸润可导致胎儿神经发育障碍。药食同源(MFH)是一种中药(TCM)概念,它有效地将食物功能和药用效果结合在一起。然而,以前没有研究筛选、预测和验证 MFH 草药治疗 ASD 的潜在靶点。因此,在这项研究中,我们使用综合的生物信息学方法对 MFH 草药和药物靶点进行了大规模的筛选和分析,确定白藜芦醇和 Thoc5 分别是治疗 MIA 诱导的 ASD 的最佳小分子成分和药物靶点。此外,体外实验结果表明,白藜芦醇增加了 Thoc5 的表达,并有效抑制了 LPS 诱导的 BV2 细胞炎症因子的产生。此外,体内实验中,白藜芦醇增加了 Thoc5 的表达,并有效抑制了 MIA 妊娠小鼠胎盘和胎脑的炎症,改善了后代的 ASD 样行为。