Inhibiting effects of rhynchophylline on zebrafish methamphetamine dependence are associated with amelioration of neurotransmitters content and down-regulation of TH and NR2B expression

Jiang, Mingjin; Chen, Yifei; Li, Chan; Peng, Qiuxian; Miao, Fei; Liu, Wei; Qun-zhao, Kang; Lin, Yingbo; Yung, Kin Lam; Mo, Zhixian

doi:10.1016/j.pnpbp.2016.03.004

Cited by 27 publications

(16 citation statements)

References 68 publications

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“…Moreover, the Rhy-driven decreases in GluN2B are often observed in parallel with improvements in cognitive functions in rodents, such as spatial memory or drug-conditioned place preference (CPP) [ 20 , 83 , 93 ]. Similar findings were made in the zebrafish, in which Rhy was found to reduce the meth-induced increase in GluN2B protein level and CPP [ 88 ]. In contrast to the aforementioned studies, Rhy was shown to increase GluN2B protein in human mesenchymal cells [ 78 ].…”

Section: Rhy Targets and Links To Sleep Regulationsupporting

confidence: 76%

“…In this last study, dopamine (DA) release was increased in all these brain regions after Rhy administration [ 61 ]. Furthermore, Rhy was reported to rescue the amph-induced decrease of ACh, and the amph- and meth-induced increase in DA [ 88 , 91 ]. Rhy was also shown to attenuate the elevated DA and D2 receptor levels in the striatum of a rat Tourette syndrome model [ 96 ].…”

Section: Rhy Targets and Links To Sleep Regulationmentioning

confidence: 99%

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Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

et al. 2021

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Uncaria rhynchophylla is a plant highly used in the traditional Chinese and Japanese medicines. It has numerous health benefits, which are often attributed to its alkaloid components. Recent studies in humans show that drugs containing Uncaria ameliorate sleep quality and increase sleep time, both in physiological and pathological conditions. Rhynchophylline (Rhy) is one of the principal alkaloids in Uncaria species. Although treatment with Rhy alone has not been tested in humans, observations in rodents show that Rhy increases sleep time. However, the mechanisms by which Rhy could modulate sleep have not been comprehensively described. In this review, we are highlighting cellular pathways that are shown to be targeted by Rhy and which are also known for their implications in the regulation of wakefulness and sleep. We conclude that Rhy can impact sleep through mechanisms involving ion channels, N-methyl-d-aspartate (NMDA) receptors, tyrosine kinase receptors, extracellular signal-regulated kinases (ERK)/mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K)/RAC serine/threonine-protein kinase (AKT), and nuclear factor-kappa B (NF-κB) pathways. In modulating multiple cellular responses, Rhy impacts neuronal communication in a way that could have substantial effects on sleep phenotypes. Thus, understanding the mechanisms of action of Rhy will have implications for sleep pharmacology.

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Section: Rhy Targets and Links To Sleep Regulationsupporting

confidence: 76%

Section: Rhy Targets and Links To Sleep Regulationmentioning

confidence: 99%

Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

et al. 2021

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“…Suitable rats were divided into three groups of ten randomly, including control group, methamphetamine group, and rhynchophylline treatment groups. The method of the CPP paradigm was copied from our previous reports [ 21 , 22 ] and is shown in Figure 1 .…”

Section: Methodsmentioning

confidence: 99%

Expression of miRNAs in Serum Exosomes versus Hippocampus in Methamphetamine‐Induced Rats and Intervention of Rhynchophylline

Lin

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Objective To compare the expressions of miRNAs (microRNAs) in serum exosomes and in hippocampus and to provide insights into the miRNA-mediated relationship between peripheral and central nervous systems in the presence of methamphetamine. Methods Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine were replicated. The expressions of miRNAs in serum exosomes and hippocampus were determined by gene-chip sequencing. We then predicted the potential target genes of selected, differentially expressed (DE) miRNAs and then carried out functional analysis of these target genes. We also verified our results by RT-qPCR. Results Methamphetamine reward could greatly increase the activity time and distance in the intrinsically nonpreferred side of the behavioral apparatus compared with control rats (P < 0.01). Rhynchophylline treatment significantly counteracted these changes (P < 0.01). Methamphetamine-induced CPP upregulated 23 miRNAs (log2 fold change [FC] > 1, P < 0.01) in serum exosomes, whereas rhynchophylline treatment could downregulate these miRNAs (log2 FC < −1, P < 0.01). Analysis of hippocampal miRNAs profiles found 22 DE miRNAs (log2 FC > 1 or <−1, P < 0.01). When methamphetamine induced CPP, 11 of those miRNAs were upregulated, whereas rhynchophylline treatment could downregulate these miRNAs. The other 11 miRNAs behaved in the opposite way. We selected six DE miRNAs from each of serum exosomes and hippocampus for target gene prediction and functional analysis. We found that, in both, the DE miRNAs and their target genes may be related to neuronal information transmission and synaptic transmission. Conclusions Rhynchophylline blocked the alteration of behavior and the expression of some DE miRNAs induced by methamphetamine. The biological functions of these DE miRNAs target genes are correlated between serum exosomes and hippocampus. As to these biological processes and pathways which are involved in the development of addiction at multiple stages, we speculate that these DE miRNAs in serum exosomes and hippocampus are closely related to methamphetamine addiction.

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“…ex Havil., exerts strong inhibitory effects on drug addiction. Our previous studies demonstrated that Rhy can reverse the conditioned place preference (CPP) effect induced by Meth in rats and zebrafish [8,9]. In addition to antiaddictive effect, Rhy is often used to treat cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicle-Encapsulated miR-183-5p from Rhynchophylline-Treated H9c2 Cells Protect against Methamphetamine-Induced Dependence in Mouse Brain by Targeting NRG1

Zhou

Shilin

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Methamphetamine (Meth) is a highly addictive substance and the largest drug threat across the globe. There is evidence to indicate that Meth use has serious damage on central nervous system (CNS) and heart in several animal and human studies. However, the connection in the process of Meth addiction between these two systems has not been determined. Emerging data suggest that extracellular vesicles (EVs) carrying behavior-altering microRNA (miRNAs) play a crucial role in cell communication between CNS and peripheral system. Rhynchophylline (Rhy), an antiaddictive alkaloid, was used to protect the brain and heart from Meth-induced damage, which has caught our attention. Here, we used Meth-dependent conditioned place preference (CPP) animal model and cell model to verify the protective effect of Rhy-treated EVs. Further, small RNA sequencing analysis, qPCR, dual-luciferase reporter assay, and transfection test were used to identify the key EVs-encapsulated miRNAs, isolated from cultured H9c2 cells with different treatments, involved in the therapeutic effect and the underlying mechanisms of Rhy. The results demonstrate that Rhy-treated EVs exert protective effects against Meth dependence through the pathway of miR-183-5p-neuregulin-1 (NRG1). Our collective findings provide novel insights into the roles of EVs miRNAs in Meth addiction and support their potential application in the development of novel therapeutic approaches.

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Inhibiting effects of rhynchophylline on zebrafish methamphetamine dependence are associated with amelioration of neurotransmitters content and down-regulation of TH and NR2B expression

Cited by 27 publications

References 68 publications

Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

Expression of miRNAs in Serum Exosomes versus Hippocampus in Methamphetamine‐Induced Rats and Intervention of Rhynchophylline

Extracellular Vesicle-Encapsulated miR-183-5p from Rhynchophylline-Treated H9c2 Cells Protect against Methamphetamine-Induced Dependence in Mouse Brain by Targeting NRG1

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