Parent-administered pediatric tuina for the treatment of attention deficit hyperactivity disorder symptoms: Process evaluation of a pilot randomized controlled trial.

BACKGROUND: A pilot randomized controlled trial (RCT) was conducted in mainland China to examine the feasibility, acceptability, and preliminary effects of parent-administered pediatric tuina on attention deficit hyperactivity disorder (ADHD) symptoms in preschool children. An embedded process evaluation was performed to explore barriers and facilitators in the implementation, identify additional questions, and refine the study design for a future fully powered study. METHODS: The process evaluation comprises the following parts: (a) self-reported questionnaires on parents (n = 43), traditional Chinese medicine (TCM) practitioners (n = 2), outcome assessor (n = 1), and research assistant (n = 1); (b) parent logbook on parent-administered pediatric tuina (n = 32); and (c) focus group interview sessions (n = 15). Accomplishment of the self-report questionnaires was voluntary for all participants and compulsory for research personnel and TCM practitioners. The parent logbook on the intervention was filled out by all participants in the intervention group. Participants of focus group interviews were selected via purposive sampling, and data were analyzed with template analysis. Qualitative findings were summarized in tables, while the mean was calculated to reflect the quantitative findings. RESULTS: Perceived benefits, acceptability of parents and children, and professional support from the research team facilitated the implementation of the intervention. Meanwhile, the TCM pattern identification using online mode may limit the accuracy and lead to parents doubting the precision of the TCM pattern. This limitation was regarded as a major barrier. Parents perceived improvements in terms of children's appetite, sleep quality, and parent-child relationship. Participants were generally satisfied with the settings of parent-administered pediatric tuina and showed satisfactory adherence to the implementation. CONCLUSIONS: Implementation of parent-administered pediatric tuina intervention is feasible and acceptable. The intervention can be refined by improving the TCM pattern identification procedure and adjusting outcome settings in a fully powered study in the future.

Astragaloside IV ameliorates neuroinflammation-induced depressive-like behaviors in mice via the PPARγ/NF-κB/NLRP3 inflammasome axis.

Major depressive disorder is a common but devastating mental disorder, and recent evidence shows that neuroinflammation may play a pivotal role in the etiology of depression. Astragaloside IV (AS-IV) is an active component purifed from Astragalus membranaceus (Fisch) Bge, which has shown anti-inflammatory, anti-oxidative and anti-apoptotic effects. In this study, we explored whether AS-IV produced antidepressant effects via its inhibition of neuroinflammation in mouse models of depression. Depressive-like behaviors including decreased sucrose consumption, reduced locomotor activity and increased immobility time were induced in mice using repeated restraint stress (RRS). We found that administration of AS-IV (16, 32 and 64 mg·kg-1·d-1, ig) significantly attenuated RRS-induced depressive-like behaviors. Furthermore, AS-IV administration significantly reduced the levels of TNF-α and IL-1ß, increased PPARγ expression and GSK3ß phosphorylation, decreased NF-κB phosphorylation, and reduced NOD-, LRR- and pyrin domain-containingprotein 3 (NLRP3) inflammasome and caspase-1 p20 generation in the hippocampus of the mice. LPS-induced depression-like behaviors were induced by LPS injection (1 mg·kg-1·d-1, ip), which were ameliorated by administration of AS-IV (20, 40 mg·kg-1·d-1, ig). The results of the LPS-induced mouse model were in accordance with those acquired from the RRS-induced mouse model: LPS injection significantly increased TNF-α and IL-1ß expression in the mouse hippocampus, which was reversed by administration of AS-IV. Moreover, administration of AS-IV significantly increased PPARγ expression and GSK3ß phosphorylation, and decreased NF-κB phosphorylation and NLRP3 inflammasome. These results suggest that AS-IV is a potential drug against depression, and its antidepressant effects are partially mediated by inhibition of neuroinflammation via the upregulation of PPARγ expression.

Anti-amyloidgenic and neurotrophic effects of tetrahydroxystilbene glucoside on a chronic mitochondrial dysfunction rat model induced by sodium azide.

Alzheimer's disease (AD) is an irreversible neurodegenerative brain disorder with complex pathogenesis. Emerging evidence indicates that there is a tight relationship between mitochondrial dysfunction and ß-amyloid (Aß) formation. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) is one of the main active components extracted from Polygonum multiflorum. The purpose of the present study was to investigate the effects of TSG on Aß production and neurotrophins in the brains of rats by using a mitochondrial dysfunction rat model induced by sodium azide (NaN3), an inhibitor of mitochondrial cytochrome c oxidase (COX). NaN3 was administered to rats by continuous subcutaneous infusion for 28 days via implanted osmotic minipumps to establish the animal model. TSG was intragastrically administered starting 24 h after the operation. The activity of mitochondrial COX was measured by a biochemical method. The content of Aß 1-42 was detected by ELISA. The expression of neurotrophic factors was determined by Western blot and immunohistochemistry. The results showed that NaN3 infusion for 28 days induced a decrease in mitochondrial COX activity, an increase in Aß 1-42 content and the expression of amyloidogenic ß-amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1) and presenilin 1 (PS1), and a decline in the expression of neurotrophins in the hippocampus of rats. Intragastrical administration of TSG elevated mitochondrial COX activity, decreased Aß 1-42 content and the expression of APP, BACE1 and PS1, and enhanced the expression of nerve growth factor, brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of NaN3-infused rats. These findings suggest that TSG may be beneficial in blocking or slowing the progression of AD by enhancing mitochondrial function, decreasing Aß production and increasing neurotrophic factors at some extent.

[Effects of icariin on beta-amyloid and neurotrophic factors in brain of mitochondrial deficiency model rats].

The purpose of the present study was to investigate the effects of icariin (ICA) on the content of beta-amyloid (Abeta) and the expression of neurotrophic factors in the brain of mitochondrial deficiency model rats. SD rats were infused subcutaneously with sodium azide, which is an inhibitor of mitochondrial respiratory chain complex IV, via a minipump (0. 5 mg . kg-1 h-1) for 28 days to establish the mitochondrial deficiency animal model. The activity of mitochondrial respiratory chain complex IV (i. e. cytochrome C oxidase, COX) in hippocampus was measured by biochemical methods. ELISA method was used to detect the content of Abeta in the brain. The expression of neurotrophic factors was detected by Western blot and immunohistochemistry methods. Image analysis was performed by Image-pro software. The results showed that chronic infusion of sodium azide by minipump induced a significant decrease in the activity of mitochondrial cytochrome C oxidase, an obvious increase in the content of Abeta, and a marked decline in the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the brain of rats. Intragastrical administration of ICA (12 or 36 mg . kg-l) significantly ameliorated all these abnormalities in the model rats. In conclusion, ICA can increase mitochondrial activity, inhibit Abeta production, and enhance the expression of neurotrophic factors in the brain of model rats induced by sodium azide. The results suggested that ICA may have beneficial prospect for the treatment of Alzheimer's disease.

[Effects of Shenwu capsule on learning-memory ability and cholinergic function of brain in AD-like rat model induced by chronic infusion of sodium azide by minipump].

Because of the proposed importance of mitochondrial cytochrome C oxidase (COX) decrease in Alzheimer's disease (AD) , the protective effect of Shenwu capsule on mitochondrial deficiency model rats and its pharmacological mechanism were investigated in present study. Rats were administered with azide at 1 mg . kg-1 . h-1 subcutaneously via an Alzet minipump for 30 days. Tweny-four hours after the operation, the rats were administered intragastrically by Shenwu capsule with the dose of 0. 45, 0. 9 and 1. 8 g . kg-1 . d-1 for one month. Then learning-memory ability was determined by the watermaze test and passive avoidance tests. The activity of choline-acetyl-transfertase(ChAT) and acetylcholinesterase (AChE) in hippocampus and cortex of rats were measured by radiochemical method and hydroxylamine colorimetry separately. M-cholinergic receptor binding ability (M-binding) was assayed by radio binding. Chronic infusion of sodium azide via minipump induced learning-memory deficiency of rats. Both ChAT activity and M-binding decreased in hippocampus and cortex of model rats, however, the activity of AChE increased in hippocampus and was not affected at the cortex. As the result, the cholinergic function of the brain decreased in model rats. Shenwu capsule significantly improved learning and memory ability and the mechanism may be related with the improved cholinergic function in model brain: ChAT activity and M-binding significantly increased in Shenwu treated groups compared with model group; and the increased activity of AChE in hippocampus returned to normal. Mitochondria, especially mitochondrial cytochrome C oxidase, may play the key role in the early event of AD. Chronic, partial in vivo inhibition of mitochondrial cytochrome C oxidase in rats provides a suitable model mimicking several aspects of AD. Shenwu capsule indicate effectiveness in AD-like mitochondrial deficiency model rats, so it would be applied in the treatment of AD.