scholarly journals Cannabidiol attenuates methamphetamine-induced conditioned place preference via the Sigma1R/AKT/GSK-3β/CREB signaling pathway in rats

2020 ◽  
Vol 9 (3) ◽  
pp. 202-211 ◽  
Author(s):  
Genmeng Yang ◽  
Liu Liu ◽  
Ruilin Zhang ◽  
Juan Li ◽  
Chi-Kwan Leung ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Conditioned Place Preference ◽  
Intraperitoneal Injection ◽  
Brain Regions ◽  
Cellular Protein ◽  
Place Preference ◽  
Therapeutic Effects ◽  
Expression Levels ◽  
Dose Dependent Fashion ◽  
Gsk 3Β

Abstract Methamphetamine (METH) is a highly addictive psychostimulant. Cannabidiol (CBD) is an exogenous cannabinoid without psychostimulating activity, which has potential therapeutic effects on opioid addiction. However, it is unclear whether CBD has therapeutic effects on METH-induced motivational effects. The present study examines whether CBD has a protective effect on METH-induced conditioned place preference (CPP) in rats by regulating the Sigma1R and AKT-GSK3β-CREB signaling pathway. Seventy rats were equally and randomly divided into seven groups. The rat CPP model was established via the intraperitoneal injection (IP) of 2 mg/kg of METH. Next, the intraperitoneal injection of 10, 20, 40, and 80 mg/kg CBD was performed 1 h prior to the injection of saline or METH. The protein expression levels of Sigma1R, AKT, p-AKT, GSK-3β, p-GSK-3β, CREB, and p-CREB in the rats’ prefrontal cortex, nucleus accumbens, and hippocampus and ventral tegmental were detected using western blot analysis. CBD was found to inhibit METH-induced CPP in a dose-dependent fashion. The expression levels of Sigma1R, p-AKT, p-GSK3β, and p-CREB increased significantly in the METH-induced CPP model. Treatment involving different doses of CBD caused differential inhibitory responses in the cellular protein abundance of Sigma1R, p-AKT, p-GSK3β, and p-CREB across various brain regions. The present study found that METH can induce CPP in rats. When a pretreatment of CBD is applied, the CBD can weaken CPP in METH-induced rats by regulating the SigmaR1/AKT/GSK-3β/CREB signaling pathway. The results of this study indicate that CBD has a potential therapeutic effect on METH-induced rewarding effects.

scholarly journals Erratum to: Cannabidiol attenuates methamphetamine-induced conditioned place preference via the Sigma1R/AKT/GSK-3β/CREB signaling pathway in rats

2020 ◽  
Vol 9 (4) ◽  
pp. 588-588
Author(s):  
Genmeng Yang ◽  
Liu Liu ◽  
Ruilin Zhang ◽  
Juan Li ◽  
Chi-Kwan Leung ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Conditioned Place Preference ◽  
Place Preference ◽  
Gsk 3Β

scholarly journals Apigenin Attenuates Acetaminophen-Induced Hepatotoxicity by Activating AMP-Activated Protein Kinase/Carnitine Palmitoyltransferase I Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiaqi Zhang ◽  
Xiaoqiang Liang ◽  
Jiacheng Li ◽  
Hao Yin ◽  
Fangchen Liu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Carnitine Palmitoyltransferase ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Compound C ◽  
Carnitine Palmitoyltransferase I ◽  
Gsk 3Β ◽  
Amp Activated Protein Kinase

Overuse of acetaminophen (APAP) is a major cause of drug-induced liver failure at the clinics. Apigenin (API) is a natural flavonoid derived from Matricaria chamomilla. The aim of the present study was to investigate the amelioration function of API in APAP-induced hepatotoxicity both in vitro and in vivo and investigate its potential mechanisms. Analysis results of the activities of serum alanine and aspartate aminotransferases (ALT and AST), malondialdehyde, myeloperoxidase (MPO), and reactive oxygen species (ROS) demonstrated therapeutic effects of API. MTT assay results revealed that API attenuated APAP and its metabolic product, N-acetyl-p-benzoquinone imine (NAPQI) induced cytotoxicity in a dose-dependent manner in human liver cells, L-02 cells. Subsequently, metabolomic results of cells and serum analyses demonstrated an aberrant level of carnitine palmitoyltransferase I (CPT1A). We established that API stimulated CPT1A activity in mice liver tissues and L-02 cells. Molecular docking analyses revealed potential interaction of API with CPT1A. Further investigation of the role of CPT1A in L0-2 cells revealed that API reversed cytotoxicity via the AMP-activated protein kinase (AMPK)/GSK-3β signaling pathway and compound C, which is a selective AMPK inhibitor, inhibited activation of CPT1A induced by API. API was bound to the catalytic region of AMPK as indicated by molecular docking results. In addition, compound C suppressed nuclear translocation of nuclear factor erythroid 2–related factor 2 (NRF2) that is enhanced by API and inhibited the antioxidative function of API. In summary, the study demonstrates that API attenuates APAP-induced hepatotoxicity by activating the AMPK/GSK-3β signaling pathway, which subsequently promotes CPT1A activity and activates the NRF2 antioxidant pathway.

scholarly journals Oleanolic Acid Alleviates Cerebral Ischemia/Reperfusion Injury via Regulation of the GSK-3β/HO-1 Signaling Pathway

2021 ◽  
Vol 15 (1) ◽  
pp. 1
Author(s):  
Kaili Lin ◽  
Zhang Zhang ◽  
Zhu Zhang ◽  
Peili Zhu ◽  
Xiaoli Jiang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Oleanolic Acid ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Heme Oxygenase 1 ◽  
Therapeutic Effects ◽  
Gsk 3Β

Oleanolic acid (OA), a bioactive ingredient of Panax ginseng, exhibits neuroprotective pharmacological effects. However, the protective role of OA in cerebral ischemia and involved mechanisms remain unclear. This study attempted to explore the therapeutic effects of OA both in vitro and in vivo. OA attenuated cytotoxicity and overproduction of intracellular reactive oxygen species (ROS) by regulation of glycogen synthase kinase-3β (GSK-3β)/heme oxygenase-1 (HO-1) signal in oxygen-glucose deprivation/reoxygenation (OGD/R)-exposed SH-SY5Y cells. Additionally, OA administration significantly reduced the area of cerebral infarction and the neurological scores in the rat models of cerebral ischemia with middle cerebral artery occlusion (MCAO). The OA administration group showed a higher percentage of Nissl+ and NeuN+ cells, along with lower TUNEL+ ratios in the infarct area of MCAO rats. Moreover, OA administration reduced ROS production while it suppressed the GSK-3β activation and upregulated the HO-1 expression in infarcted tissue. Our results illustrated that OA significantly counteracted cerebral ischemia-mediated injury through antioxidant effects induced by the regulation of the GSK-3β/HO-1 signaling pathway, implicating OA as a promising neuroprotective drug for the therapy of ischemic stroke.

GSK-3β inhibition confers cardioprotection associated with the restoration of mitochondrial function and suppression of endoplasmic reticulum stress in sevoflurane preconditioned rats following ischemia/reperfusion injury

Perfusion ◽  
2018 ◽  
Vol 33 (8) ◽  
pp. 679-686 ◽  
Author(s):  
Yujia Wang ◽  
Chunlin Ge ◽  
Junfeng Chen ◽  
Kun Tang ◽  
Jianjun Liu
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Mitochondrial Function ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Expression Levels ◽  
Sevoflurane Preconditioning ◽  
Gsk 3Β

Background: Sevoflurane has been shown to protect against myocardial ischemia/reperfusion (I/R) injury in animals, while its cardioprotection is lost if the ischemic insult is too long. In this study, we proposed a prevailing hypothesis that GSK-3β inhibitor-mediated activation of GSK-3β/β-catenin signaling pathway provides additional cardioprotection in sevoflurane preconditioned rats following I/R injury. Methods: Rats were subjected to treatment with TDZD-8, a GSK-3β inhibitor, 5 minutes prior to sevoflurane preconditioning and 30-minute ischemia and 120-minute reperfusion. Furthermore, in order to find out whether this cardioprotection is linked with mitochondrial function and endoplasmic reticulum stress (ERS), we isolated mitochondria from rat hearts perfused with TDZD-8 and determined the alternations of ERS markers. Results: Sevoflurane preconditioning or GSK-3β inhibitor treatment prevented cardiomyocyte apoptosis, phosphorylated GSK-3β and accelerated total β-catenin expression levels, reduced mitochondrial permeability transition pore (MPTP) activity, promoted the recovery of mitochondrial membrane potential and decreased the expression levels of GRP78, caspase-12 and C/EBP homology protein (CHOP) in rats under I/R condition, suggesting sevoflurane preconditioning or TDZD-8 activate the GSK-3β/β-catenin signaling pathway, improve mitochondria function and suppress ERS occurrence. Conclusions: Taken together, the findings obtained from the study support the concept that sevoflurane preconditioning confers cardioprotection against myocardial I/R injury and GSK-3β/β-catenin signaling activation mediated by TDZD-8 as a novel target to prolong cardioprotection by sevoflurane anaesthesia.

scholarly journals Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer

2018 ◽  
Author(s):  
Lijing Zhang ◽  
Xiaobo Sun ◽  
Jianyong Si ◽  
Guangzhi Li ◽  
Li Cao
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Gastric Epithelium ◽  
Gastric Cancer Cells ◽  
Expression Levels ◽  
Ferula Sinkiangensis ◽  
Gsk 3Β

AbstractThe traditional herb medicine Ferula sinkiangensis K. M. Shen (F. sinkiangensis) has been used to treat stomach disorders in Xinjiang District for centuries. Umbelliprenin is the effective component isolated from F. sinkiangensis which is particularly found in plants of the family Ferula. We previously reported the promising effects of Umbelliprenin against gastric cancer cells, but its anti-migration effect remained unknown. Here we investigated the anti-migration effect and mechanism of Umbelliprenin in human gastric cancer cells. In SRB assay, Umbelliprenin showed cytotoxic activities in the gastric cancer cell lines AGS and BGC-823 in a dose-and-time-dependent manner, while it showed lower cytotoxic activity in the normal gastric epithelium cell line GES-1. During transwell, scratch and colony assays, the migration of tumor cells was inhibited by Umbelliprenin treatment. The expression levels of the Wnt-associated signaling pathway proteins were analyzed with western blots, and the results showed that Umbelliprenin decreased the expression levels of proteins of the Wnt signalling pathway, such as Wnt-2, β-catenin, GSK-3β, p-GSK-3β, Survivin and c-myc. The translocation of β-catenin to the nucleus was also inhibited by Umbelliprenin treatment. In TCF reporter assay, the transcriptional activity of T-cell factor/lymphoid enhancer factor (TCF/LEF) was decreased after Umbelliprenin treatment. Thein vivo results suggested that Umbelliprenin induced little to no harm in the lung, heart and kidney. Overall, these data provided evidence that Umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by disturbing the Wnt signaling pathway.

scholarly journals Cannabidiol Attenuates Methamphetamine-Induced Cardiac Inflammatory Response and Necrosis through The PKA/CREB Signaling Pathway

2021 ◽  
Author(s):  
Qianyun Nie ◽  
Wenjuan Dong ◽  
Baoyu Shen ◽  
Genmeng Yang ◽  
Hao Yu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Troponin I ◽  
Weight Ratio ◽  
Public Health Problem ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Expression Levels

Abstract Methamphetamine (MA) abuse is a major global public health problem, with cardiovascular issues becoming an increasingly recognized complication. Cannabidiol (CBD) has gained recent attention, due to its various pharmacological properties. However, whether CBD has therapeutic effects on MA-induced cardiotoxicity remains unknown. In the present study, we investigated whether CBD has a protective or therapeutic effect on MA-induced cardiac damage in rats via the protein kinase A (PKA)/cyclic adenosine monophosphate response element-binding (CREB) signaling pathway. Thirty rats were randomly divided into five groups. The rats were administered MA by intraperitoneal injection (IP) once a day for 4 weeks, with CBD (40 or 80 mg/kg, IP) treatment 1 h prior to the MA injections. Body and heart weights were measured, and morphological changes were determined using hematoxylin & eosin and Masson’s trichrome staining. The serum levels of interleukin-6 (IL-6) and IL-10 were detected using enzyme linked immunosorbent assay (ELISA) kits. The protein expression levels of PKA, phospho-PKA (p-PKA), CREB, phospho-CREB (p-CREB) and cardiac troponin I (cTnI) in the myocardium were detected by western blot analysis. Results showed that the heart-to-body weight ratio increased significantly following MA administration but decreased with CBD treatment. Chronic administration of MA resulted in a cardiac inflammatory response and progressive development of fibrosis, while CBD treatment attenuated these lesions in a dose-dependent manner. MA administration increased IL-6 but decreased IL-10 levels, which were reversed by CBD pretreatment. Moreover, MA significantly increased the cTnI level, but this was decreased by CBD treatment at 80 mg/kg. The protein expression levels of PKA, p-PKA, CREB, and p-CREB increased following MA administration, but significantly decreased with CBD treatment. Overall, these results indicate that chronic MA administration leads to cardiotoxicity, including cardiac inflammatory response, fibrosis, and myocardial necrosis, but these effects can be attenuated by CBD pretreatment. Our research suggests a potential application of CBD for MA-induced cardiotoxicity, which may attenuate inflammatory response and necrosis through the PKA/CREB signaling pathway.

Conditioned place preference of kisspeptin-10

2021 ◽  
Vol 19 (1) ◽  
pp. 47-53
Author(s):  
Ilia Yu. Tissen ◽  
Polina A. Chepik ◽  
Andrei A. Lebedev ◽  
Leila A. Magarramova ◽  
Eugenii R. Bychkov ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Open Field Test ◽  
Physiological Saline ◽  
Preference Test ◽  
Brain Regions ◽  
Place Preference ◽  
Male Rats ◽  
Plus Maze ◽  
Male Wistar Rats ◽  
Positive State

INTRODUCTION: Kisspeptins (KISS), a group of brain neuropeptides are involved in sexual behavior. KISS activate the hypothalamic neurons that synthesize gonadotropin releasing hormone. KISS was also detected in the limbic system. Earlier, we showed the activation of sexual motivation after the administration of kisspeptin-10 without increasing the level of testosterone in male rats, which suggests the extrahypothalamic effect of KISS. The aim of this work was to study the possibility of aquisition of conditioned place preference of kisspeptin-10, as well as to study the emotional and investigational behavior in rats after intranasal peptide administration. METHODS: Conditioned place preference test (CPP), open field test (OP) and elevated plus maze (EPM) were used in male Wistar rats. RESULTS: When studying CPP, animals spent 78.6 6.3% of the time in the chamber associated with the administration of KISS compared to control animals with administration of physiological saline (51.2% of the experiment time; p 0.05). After kisspeptin-10 administration locomotor activity was 2-fold increased (p 0.05), and the number of sniffings was 2-fold increased too (p 0.05). The parameters did not significantly differ in animals treated with kisspeptin or saline in PCL. CONCLUSION: Thus repeated intranasal administration of kisspeptin-10 induces the aquisition of CPP in rats. This suggests that kisspeptin-10 can cause activity in the reward system or the activation of brain regions associated with this system, which ultimately leads to the formation of an emotionally positive state.

Lithium chloride disrupts consolidation of morphine-induced conditioned place preference in male mice: The nitric oxide/cyclic GMP signaling pathway

2011 ◽  
Vol 219 (2) ◽  
pp. 240-247 ◽  
Author(s):  
Amirali Kiyani ◽  
Mehrak Javadi-Paydar ◽  
Hoda Mohammadkhani ◽  
Behnaz Esmaeili ◽  
Ahmad Reza Dehpour
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Conditioned Place Preference ◽  
Lithium Chloride ◽  
Cyclic Gmp ◽  
Place Preference ◽  
Male Mice

scholarly journals Effects and Mechanisms of Jinniu Capsule on Methamphetamine-Induced Conditioned Place Preference in Rats

2018 ◽  
Vol 16 (1) ◽  
pp. 674-680 ◽  
Author(s):  
Yu Shi ◽  
Feng Wang ◽  
A-Zhen Hu ◽  
Qing-Wen Wang ◽  
Jue-Lian Wu ◽  
...  
Keyword(s):  
Single Dose ◽  
Western Blot ◽  
Signaling Pathway ◽  
Conditioned Place Preference ◽  
Blot Analysis ◽  
Place Preference ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Phosphorylation Cascade ◽  
Underlying Mechanisms

AbstractThe aim of this study was to determine the effects of Jinniu Capsule on methamphetamine (METH)-induced conditioned place preference (CPP) in rats and identify the underlying mechanisms. An intraperitoneal injection of 3 mg/kg METH was used for CPP training in rats. The effects of Jinniu Capsule following a single dose on rat CPP and repeat dosing on METH withdrawal were evaluated. Western Blot analysis was used to measure protein expression of the PI3K-AKT-mTOR signaling pathway to determine the mechanisms of Jinniu Capsule. A single dose of Jinniu Capsule did not influence METH-induced CPP in rats. However, repeat dosing for 7 days significantly promoted METH withdrawal. Furthermore, METH withdrawal activated the PI3K-AKT-mTOR signaling pathway phosphorylation cascade, and Jinniu Capsule partly blocked this cascade. Jinniu Capsule demonstrated potential in promoting METH withdrawal in a rat CPP model, which may be related to its influence on the PI3K-AKT-mTOR signaling pathway.

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