The Effect of Methylphenidate Hydrochloride Combined With Platycladi Seed Extract on Attention Deficit Hyperactivity Disorder in a Murine Model

Abstract

The study aimed to evaluate the therapeutic effect and the underlying mechanism of methylphenidate hydrochloride combined with Platycladi seed extract on attention deficit hyperactivity disorder (ADHD) in a murine model. Forty-eight SPF male SHR rats were divided into 4 groups as follows: a rat model of attention deficit hyperactivity disorder that received 10 mL/kg bw/day saline solution, a methylphenidate hydrochloride group treated with 3.75 mg/kg bw/day methylphenidate hydrochloride, a Platycladi seed extract group treated with 9 mg/kg bw/day Platycladi seed extract, a methylphenidate hydrochloride (MHCRT) combined with Platycladi seed extract group treated with 3.75 mg/kg bw MHCRT plus 9 mg/kg bw/day Platycladi seed extract. Twelve Wistar Kyoto rats were used as a normal group that received 10 mL/kg bw/day saline solution. After 14 days of treatment the combination of MHCRT and Platycladi seed extract significantly reduced the serum NE (norepinephrine) level in rats and significantly increased the DA (dopamine) and 5-HT (serotonin) levels along with improving neurobehavioral changes related with ADHD with a superior effect compared with the use of Platycladi seed extract or MHCRT alone.Regarding the protein expression level in brain tissue when associated to the standard treatment with MHCRT, Platycladi seed extract additively increased the effect of MHCRT and succeeded to significantly increase the expression of GIT1 (ARF GTPaseactivating protein), CDH13 (cadherin 13), BDNF (brain-derived neurotrophic factor), CaM (calmodulin) and NET (adrenergic transporters) and significantly decreased the expression of LPHN3 (latrophilin 3) compared with the model group. In serum, the association of Platycladi seed extract with MHCRT additively increased the effect of MHCRT alone on increasing the protein level of β-EP (betaendorphin), IP3 (inositol triphosphate) and Glu (Glutamine synthetase) and decreased PG (plakoglobin) level compared with the model group. In conclusion, Platycladi seed extract can potentiate the effect of standard MHCRT treatment by regulating the expression of neurotransmitters in an ADHD murine model. RezumatStudiul a urmărit evaluarea efectului terapeutic și mecanismul ce stă la baza acțiunii clorhidratului de metilfenidat, combinat cu extractul din semințe de Platycladi, asupra unui model murin de hiperactivitate cu deficit de atenție (ADHD). Patruzeci și opt de șobolani masculi SPF spontan hipertensivi (SHR) au fost împărțiți în 4 grupuri după cum urmează: un grup de șobolani cu ADHD care a primit 10 mL/kgc/zi ser fiziologic, un grup de șobolani care a primit 3,75 mg/kgc/zi metilfenidat, un grup de șobolani care a primit 9 mg/kgc/zi extract de semințe de Platycladi, un grup tratat cu 9 mg/kg corp/extract de semințe de Platycladi și 3,75 mg/kgc metilfenidat (MHCRT). Doisprezece șobolani Wistar Kyoto au fost folosiți ca și grup normal care a primit 10 mL/kgc/zi ser fiziologic. După 14 zile de tratament, combinația utilizată a redus semnificativ nivelul seric de NE (norepinefrină) la șobolani și a...

Ketogenic diet ameliorates attention deficit hyperactivity disorder in rats via regulating gut microbiota

“…To investigate the effect of KD on brain nervous system, we determined the effect of KD on the expression of neurotransmitters, including biogenic amines 5-HT and NE, and their downstream G protein effectors and second messengers, such as AC and cAMP, respectively [ 22 ]. ELISA analysis of brain tissues showed that the concentrations of 5-HT, NE, AC, and cAMP were significantly lower in SHR than WKY rats ( Fig 2A ), which is consistent with other studies [ 23 , 24 ]. Moreover, compared with the ND group, a significant boost in the concentrations of 5-HT, NE, AC, and cAMP in the MPH and KD group were observed, both in SHR and WKY rats ( Fig 2A ).…”

“…In our study, the concentrations of 5-HT, NE, AC, and cAMP of SHR in the KD group were strikingly higher than that in the ND group. These results are consistent with previous two studies [ 23 , 24 ]. Moreover, we also proved that the expressions of DRD1, DAT, cAMP, PKA, and DARPP32 were upregulated after KD treatment.…”

Natural products of relevance in the management of attention deficit hyperactivity disorder

“…Attention deficit hyperactivity disorder (ADHD) is an increasingly common neurodevelopmental disorder, characterized by motor hyperactivity, attention deficit disorders, distraction, impulsive behavior, learning disorders along with problems in relationships with others (Figure 1) (Belousova, 2003;J. H. Zhao et al, 2021).…”

“…Attention deficit hyperactivity disorder (ADHD) is an increasingly common neurodevelopmental disorder, characterized by motor hyperactivity, attention deficit disorders, distraction, impulsive behavior, learning disorders along with problems in relationships with others (Figure 1) (Belousova, 2003; J. H. Zhao et al, 2021). It affects approximately 8%–12% of children worldwide (Luo et al, 2019), with ~2–3 million children have been diagnosed in the United States (Brue & Oakland, 2002).…”