You Longtai, Peng Hulinyue, Liu Jing, Sai Na, Zhao Wenwen, Li Xiao, Yang Chunjing, Guo Peng, Ni Jian
Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, PR China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China.
Phytomedicine. 2025 Jun 18;145:157007. doi: 10.1016/j.phymed.2025.157007.
Recently, research interest in attention deficit hyperactivity disorder (ADHD) has grown significantly, driven by its increasing incidence and substantial societal impact. Among the various pathogenic mechanisms under investigation, the microbiota-gut-brain axis has emerged as a crucial area of focus. In the context of ADHD treatment, Xiaoer Huanglong Pellets (XRHLP), a traditional Chinese herbal formulation, have demonstrated therapeutic efficacy, although the underlying mechanisms remain partially understood.
This study aimed to analyze and compare the therapeutic effects and underlying mechanisms of XRHLP, including gastric release (WR_HL), enteric release (CR_HL), and colon release (JCR_HL) pellets, for ADHD treatment.
This study employed a multi-modal approach to investigate the effects of XRHLP on ADHD. Behavioral assessments combined with Enzyme-linked immunosorbent assay and Western-blot analyses were conducted to evaluate the therapeutic outcomes in model rats with ADHD. Comprehensive profiling of the gut-brain axis was performed using 16S ribosomal RNA sequencing and untargeted and targeted metabolomic analyses. The causal role of the gut microbiota was further validated using fecal microbiota transplantation (FMT).
WR_HL, CR_HL, and JCR_HL improved ADHD-like behaviors and neurotransmission dysfunction, with JCR_HL exhibiting superior intervention effects compared to WR_HL and CR_HL. These therapeutic effects are mediated through multiple pathways, including the restoration of gut microbial homeostasis, attenuation of inflammatory cascades, and repair of compromised intestinal and blood-brain barrier. The intervention also corrected systemic metabolic imbalances by specifically addressing the abnormalities in amino acid metabolism, neurotransmitter regulation, and short-chain fatty acid production. FMT experiments further confirmed the critical role of microbial modulation in mediating the behavioral and microbial regulatory effects of XRHLP.
In summary, XRHLP exerts anti-ADHD effects by improving the microbiota-gut-brain axis and correcting amino acid metabolic disorders, providing new insights into the molecular mechanisms by which traditional Chinese medicine influences ADHD and offers potential avenues for drug development.
近年来，由于注意力缺陷多动障碍（ADHD）的发病率不断上升及其对社会的重大影响，对该疾病的研究兴趣显著增加。在各种正在研究的致病机制中，微生物群-肠道-脑轴已成为一个关键的研究焦点。在ADHD治疗方面，小儿黄龙颗粒（XRHLP）作为一种传统中药制剂，已显示出治疗效果，但其潜在机制仍部分不明。
本研究旨在分析和比较XRHLP的胃溶型（WR_HL）、肠溶型（CR_HL）和结肠溶型（JCR_HL）颗粒对ADHD治疗的效果及其潜在机制。
本研究采用多模式方法研究XRHLP对ADHD的影响。通过行为评估结合酶联免疫吸附测定和蛋白质免疫印迹分析，评估ADHD模型大鼠的治疗效果。使用16S核糖体RNA测序以及非靶向和靶向代谢组学分析对肠道-脑轴进行综合分析。通过粪便微生物群移植（FMT）进一步验证肠道微生物群的因果作用。
WR_HL、CR_HL和JCR_HL均改善了ADHD样行为和神经传递功能障碍，与WR_HL和CR_HL相比，JCR_HL表现出更优的干预效果。这些治疗效果通过多种途径介导，包括恢复肠道微生物稳态、减轻炎症级联反应以及修复受损的肠道和血脑屏障。该干预还通过特异性解决氨基酸代谢、神经递质调节和短链脂肪酸产生方面的异常，纠正了全身代谢失衡。FMT实验进一步证实了微生物调节在介导XRHLP的行为和微生物调节作用中的关键作用。
总之，XRHLP通过改善微生物群-肠道-脑轴和纠正氨基酸代谢紊乱发挥抗ADHD作用，为中药影响ADHD的分子机制提供了新见解，并为药物开发提供了潜在途径。
