Effect Of Rhynchophylline On Behavior And Metabolism In ADHD Model Mice

Objective 1.To observe the effects of rhynchophylline on the behavior of ADHD model mice;2.To investigate the effects of rhynchophylline on DA metabolism and inflammatory cytokines in ADHD model mice;3.To investigate the effects of rhynchophylline on the inflammatory response of DA neurons.Methods30 male DAT-CRE mice were genotyped and identified for behavior.They were randomly divided into 5 groups with 6 mice in each group: model control group(MCK),methylphenidate group(MPH),and Ningdong granules.The groups(NDG),rhynchophylline intragastric administration(RHG)and rhynchophylline intraperitoneal injection(RHF)were administered with the exception of the model control group.12 healthy male C57 mice were randomly divided into 2 groups of 6 in each group: blank control group(CK)and blank administration group(CRH).Before administration,7 days of administration,14 days of administration,and 21 days of administration,the behavioral parameters and signs of each group of mice were monitored in the mine site experiment and the Y-maze test.After 21 days of administration,serum levels of DA,HVA,MAO,TNF-α,IL-1β,and IL-6 in serum were measured by ELISA.Statistical analysis was used to compare behavioral data with inflammatory factors.The effect of lipopolysaccharide(LPS)-induced dopaminergic neurons and glial cells on inflammatory factors(TNF-α,IL-1β)was detected by ELISA.Results(1)ADHD-associated phenotypes in DAT-CRE mice: PCR gene tests and behavioral tests showed that the mice had ADHD-like phenotypes;(2)The behavior of each group in the open-field test: Compared with the CK group,the total activity,mean velocity and upright number of ADHD mice increased significantly and reduceed the levels of the residence time in the central area(P<0.001);After alkali intervention,the residence time in the center increased significantly,the number of upright,average speed and total activity decreased significantly(P <0.001);(3)Behavior in Y maze test: Rhynchophylline could significantly improve the autonomic alternating response rate in ADHD mice(P <0.001);(4)Inter-group serum: Rhynchophylline could obviously down-regulate 3inflammatory factors in peripheral blood,raise the activity of MAO and promote the production of DA metabolite HVA,thus contributing to the metabolism of DA,and there was no difference between different administration modes significant difference;(5)In the group of cell culture medium,the levels of TNF-α and IL-1β in the LPS-mediated inflammatory group reached the peak at 3 and 6 hours.Moreover,the globle levels of TNF-α and IL-1β in the LPS-mediated inflammatory group were higher than those in LPS group(P <0.05),there was no significant difference between the LPS + rhynchophylline group and the LPS + Ningdong Granule group difference.Conclusion1.Rhynchophylline can effectively improve the hyperactivity,impulsivity and cognitive ability of ADHD model mice;2.Rhynchophylline could promote the metabolism of DA in ADHD model mice and reduce the release of cellular inflammatory factors,there was a correlation between the behavior and ADHD model mice;3.In vitro,Rhynchophylline can significantly induced the levels of LPS-induced DA neurons and glial cells inflammatory cytokines TNF-α,IL-1β,suggesting a protective role to neurons.