An Shen Ding Zhi Ling Alleviates Symptoms of Attention Deficit Hyperactivity Disorder via Anti-Inflammatory Effects in Spontaneous Hypertensive Rats

Abstract

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset chronic neurobehavioral disorder, with multiple genetic and environmental risk factors. Chronic inflammation may be critical for the progression of ADHD. An Shen Ding Zhi Ling (ASDZL) decoction, a traditional Chinese medicine prescription, is clinically used in ADHD treatment. In this study, we investigated the effects and underlying anti-inflammatory mechanisms of ASDZL in young spontaneously hypertensive rats (SHRs), a widely used model of ADHD. SHRs were divided into the SHR model group (vehicle), atomoxetine group (4.56 mg/kg/day) and ASDZL group (21.25 g/kg/day), and orally administered for four weeks. Wistar Kyoto rats were used as controls (vehicle). We found that ASDZL significantly controlled hyperactivity and impulsivity, and improved spatial memory of SHRs in the open field test and Morris water maze test. ASDZL reduced the pro-inflammatory factors interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 and increased anti-inflammatory factor IL-10 in SHRs, and decreased the activation of microglia, astrocytes and mast cells in the prefrontal cortex (PFC) and hippocampus. Furthermore, the results indicated that ASDZL inhibited the neuroinflammatory response by protecting the integrity of the blood-brain barrier and suppressing the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways of SHRs. In conclusion, these findings revealed that ASDZL attenuated ADHD symptoms in SHRs by reducing neuroinflammation.

Stilbene Glucoside Ameliorates Symptoms of Attention Deficit Hyperactivity Disorder by Regulating BDNF Signal Pathway and Inhibiting Neuro-inflammation in Spontaneous Hypertensive Rats

“…Mast cells can also induce glial cell activation and amplify neuro-in ammatory responses through PAR2-MAPK and PI3K/AKT signaling pathways (Verlaet et al, 2014, Yuan et al, 2019. Previous studies revealed that traditional chinese medicine an shen ding zhi ling improved NE and DHA de ciency in the prefrontal and striatum of SHRs (Song et al, 2020). In this study, we found that stilbene glucoside increased the levels of DHA in prefrontal tissues.…”

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

“…ASDZL is composed of 12 Chinese herbs (Cu Chai Hu, Huang Qin, Lian Qiao, Yu Jin, Jue Ming Zi, Tian Zhu Huang, Gou Teng, Sheng Di Huang, Shi Chang Pu, Dang Gui, Yi Zhi Ren, and Yuan Zhi) [ 18 ]. All herbs were provided and authenticated by Professor Jianguo Chao.…”

“…Twelve kinds of Chinese herbs were mixed with distilled water in a ratio of 1:8 and decocted twice for 2 hours each time [19]. en the above decocting solution was further concentrated into 1.37 g/mL, and UHPLC was used to analyze the components of the aqueous extract of ASDZL [18]. e weight changes in rats of five groups are shown in Table 1.…”

Enhanced Glial Reaction and Altered Neuronal Nitric Oxide Synthase are Implicated in Attention Deficit Hyperactivity Disorder

“…SHRs exhibit behaviors similar to those of ADHD patients in a variety of testing paradigms, including increased motor activity, impulsivity, and inattention. Evidences including candidate genes, neurotransmitter dysfunction, neuropathology and pharmacology supports construct validity of SHR ( Song et al, 2020 ). Meanwhile, the dopaminergic and (-)-noradrenaline systems of spontaneously hypertensive rats are hypofunctional, which is one of the important mechanisms in the pathogenesis of ADHD ( Bucci et al, 2008 ).…”

“…TNF-α, ROS and other inflammatory stimuli induce expression of NF-κB in the astrocytic nucleus and aggravate neuroinflammation ( Linnerbauer et al, 2020 ). Also, the MAPK/NF-κB signaling minimizes the activation of astrocyte and microglia, and lowers the expression of IL-1, TNF-α and other inflammatory factors in ADHD ( Song et al, 2020 ).…”