An Shen Ding Zhi Ling Ameliorates the Symptoms of Attention Deficit Hyperactivity Disorder via Modulating Brain-Derived Neurotrophic Factor-Related Signaling Pathways

Li Yaqun; Yuan Haixia; Song Yuchen; Zhu Mingxin; Lu Manqi; Tian Yunlong; Wang Aizhen; Han Xinmin

doi:10.1155/2022/5471586

An Shen Ding Zhi Ling Ameliorates the Symptoms of Attention Deficit Hyperactivity Disorder via Modulating Brain-Derived Neurotrophic Factor-Related Signaling Pathways

Evid Based Complement Alternat Med. 2022 Jul 21:2022:5471586. doi: 10.1155/2022/5471586. eCollection 2022.

Authors

Li Yaqun^{1

2

3}, Yuan Haixia^{1

4}, Song Yuchen¹, Zhu Mingxin⁴, Lu Manqi⁵, Tian Yunlong², Wang Aizhen², Han Xinmin^{1

4}

Affiliations

¹ First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
² The Affiliate Taizhou Hospital of Nanjing University of Chinese Medicine, Taizhou, China.
³ Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing, China.
⁴ Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
⁵ College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder. It may impact the cognitive and social functions throughout childhood and determine adult outcomes. Dopamine (DA) deficiency theory is the pathogenesis of ADHD that is recognized by most international literature. Existing studies have shown that DA deficiency is caused by the abnormal function of the DA transporter and an imbalance in the DA receptor functionality. Recent clinical and experimental studies have found that the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathway acts a pivotal part in DA vesicle circulation and ADHD pathogenesis. An Shen Ding Zhi Ling (ASDZL) is a traditional Chinese medicine (TCM) prescription, which was widely prescribed to treat ADHD in Jiangsu, China, but its therapeutic mechanism is unclear. Therefore, we constructed a spontaneously hypertensive rat (SHR) model to explain its mechanism. SHRs were randomly assigned to four groups: SHR model group (vehicle), methylphenidate hydrochloride group (MPH), ASDZL group, and 7,8-dihydroxyflavone group (7,8-DHF). At the same time, the above groups were given continuous medication for four weeks. The results show that ASDZL, MPH, and 7,8-DHF group could significantly improve the spatial memory of SHRs in the Morris water maze tests. ASDZL increased the levels of BDNF, TrkB, p75 neurotrophin receptor (p75), C-Jun N-terminal kinases 1 (JNK1), and nuclear factor kappa B (NF-κB) in the prefrontal cortex (PFC) and hippocampus synaptosome of SHRs. The results of this study suggest that ASDZL can relieve the symptoms of ADHD in SHRs by regulating the balance between the BDNF/TrkB signaling pathway (promoting vesicle circulation) and the BDNF/P75/JNK1/NF-κB signaling pathway (inhibiting vesicle circulation) within the PFC and hippocampus synaptosome to increase the DA concentration in the synaptic cleft. The BDNF/TrkB signal pathway within the PFC and hippocampus synaptosome was activated by 7,8-DHF to increase DA concentration in the synaptic cleft. Whether 7,8-DHF can activate or inhibit the BDNF/P75 signaling pathway remains unclear.