Pinocembrin Decreases Ventricular Fibrillation Susceptibility in a Rat Model of Depression

Ye, Tianxin; Zhang, Cui; Wu, Gang; Wan, Weiguo; Guo, Yan; Fo, Yuhong; Chen, Xiuhuan; Liu, Xin; Ran, Qian; Liang, Jinjun; Shu, Shi; Yang, Bo

doi:10.3389/fphar.2020.547966

Cited by 19 publications

(10 citation statements)

References 47 publications

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“…Wang et al (2020) have found pinocembrin could mitigate depressive-like behaviors induced by inhibiting the cell apoptosis and the pro-inflammatory factors expression). Besides, it is showed pinocembrin may decreases ventricular fibrillation susceptibility in the depression model (Ye et al , 2020), indicating that it has multiple therapeutic targets and application prospects in the future. In line with these perspectives, further studies are needed to determine the exact origins and mechanisms in the antineuroinflammatory effect of pinocembrin.…”

Section: Discussionmentioning

confidence: 99%

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus

Li¹,

Hu²,

Jiang³

et al. 2022

Behavioural Pharmacology

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Mounting evidence indicates that immune dysfunction may contribute to the neurobiology of major depressive disorder (MDD). Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) were recently reckoned pivotally to regulate NOD-like receptor protein 3 (NLRP3) in microglia. Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been studied in various animal models of human disease with anti-inflammatory and antioxidant activities. Herein, we investigated the potential antineuroinflammatory effects of pinocembrin on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. Male C57BL/6J mice were subjected to CUMS for 4 weeks, treatment group was injected with pinocembrin at a dose of 20 mg/kg. After the stress procedure, behavioral tests, including sucrose preference tests (SPTs) and tail suspension tests (TSTs) were performed to evaluate depressive-like phenotype. Subsequently, the expression of cytokines and microgliarelated inflammatory biomarkers were assessed. In the study, we found that pinocembrin significantly blocked the declination of SPT percentage and the extension of TST immobility durations in the depression mouse model. Also, we observed that pinocembrin significantly suppressed microglial activation in the hippocampus. Additionally, pinocembrin downregulated hippocampal NLRP3 through P2X7/TLR4 pathway, and also regulated the CUMS-induced imbalance of pro-inflammatory cytokines, including interleukin-1beta, tumor necrosis factor-alpha and interleukin-6. In conclusion, pinocembrin ameliorates CUMS-induced depressive-like behaviors possibly through downregulating P2X7/TLR4 pathway, providing the mechanism of antidepressant treatment. Behavioural

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Section: Discussionmentioning

confidence: 99%

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus

Li¹,

Hu²,

Jiang³

et al. 2022

Behavioural Pharmacology

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“…QT interval, QTc interval, and Tpeak–Tend interval are markers of cardiac arrhythmia. Both prolonged QT and QTc [ 14 ] and shortened QT interval and QTc [ 15 ] are associated with malignant ventricular arrhythmia (VAs). Prolonged Tpeak–Tend is associated with an elevated arrhythmic risk [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Cardiac impact of high-frequency irreversible electroporation using an asymmetrical waveform on liver in vivo

Wang

Zhang

et al. 2021

BMC Cardiovasc Disord

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Background High-Frequency Irreversible Electroporation (H-FIRE) is a novel technology for non-thermal ablation. Different from Irreversible electroporation (IRE), H-FIRE delivers bipolar electrical pulses without muscle contraction and does not cause electrolysis. Currently, little is known regarding the cardiac safety during the administration of H-FIRE on liver. The aim of this study was to evaluate the changes of electrocardiogram (ECG) and biomarkers of cardiac damage during asymmetrical waveform of H-FIRE therapy in vivo. Methods The swines (n = 7) in IRE group, which used 100 pulses (2200 V, 100–100 μs configuration), were administrated with muscle relaxant under anesthesia. In the absence of muscle relaxant, 7 swines in H-FIRE group were performed with 2400 pulses (3000 V, 5–3–3–5 μs configuration). Midazolam (0.5 mg/kg) and xylazine hydrochloride (20 mg/kg) were given to induce sedation, followed by Isoflurane (2.5%, 100% oxygen, 3 L/min) to maintain sedation in all the swines. Limb lead ECG recordings were analyzed by two electrophysiologists to judge the arrhythmia. Cardiac and liver tissue was examined by pathology technique. Results The ablation zones were larger in H-FIRE than IRE. Both IRE and H-FIRE did not affect the autonomous cardiac rhythm. Even when the electrical signal of IRE and H-FIRE fell on ventricular vulnerable period. Moreover, cTnI in IRE group showed an increase in 4 h after ablation, and decreased to baseline 72 h after ablation. However, cTnI showed no significant change during the administration of H-FIRE. Conclusions The study suggests an asymmetrical waveform for H-FIRE is a promising measure for liver ablation. The results were based on normal liver and the swines without potential cardiac diseases. With the limitations of these facts, asymmetrical waveform for H-FIRE of liver tissue seems relatively safe without major cardiac complications. The safety of asymmetrical waveform for H-FIRE needs to evaluate in future.

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“…The OFT was performed to analyze the movement of the rats as described previously ( 14 ). Briefly, the rats were placed separately in the middle of an open field (100 cm × 100 cm × 50 cm), and the behavior of the rats was recorded and analyzed by a video-tracking system (EthoVision 3.0, Noldus) for 5 min.…”

Section: Methodsmentioning

confidence: 99%

“…Pinocembrin decreased the risk of ventricular arrhythmias and reduced the myocardial infarction area in the myocardial ischemia-reperfusion rats ( 12 ). Pinocembrin decreased AF susceptibility in the myocardial infarction rats ( 13 ) and reduced ventricular fibrillation (VF) susceptibility in the depressed rats ( 14 ). However, whether pinocembrin alleviates AF susceptibility in the depressed rats is not clear.…”

Section: Introductionmentioning

confidence: 99%

Pinocembrin Decreases Atrial Fibrillation Susceptibility in a Rodent Model of Depression

Ran

Chen

Zhang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundDepression is often comorbid with cardiovascular diseases and contributes to the development and maintenance of atrial fibrillation (AF). Ample research demonstrated that pinocembrin had protective effects on the neuropsychiatric and cardiovascular systems via its pharmacological properties. However, whether pinocembrin protects from AF in depression models is not known. The present research investigated antiarrhythmic effects of pinocembrin and the underlying mechanisms in depressed rats.MethodsOne hundred and ten male Sprague Dawley rats were randomly divided into six groups: the CTL group (the normal rats administered saline), the CTP group (the normal rats administered pinocembrin), the MDD group (the depressed rats administered saline), the MDP group (the depressed rats administered pinocembrin), the MDA group (the depressed rats administered apocynin), and the MPA group (the depressed rats administered both pinocembrin and apocynin). Chronic unpredictable mild stress (CUMS) was performed for 28 days to establish the depression model. Pinocembrin was administered via gavage from Day 8 to Day 28, and apocynin was administered via intraperitoneal injection from Day 1 to Day 28. The effects were evaluated using behavioral measurements, in vitro electrophysiological studies, whole-cell patch-clamp recordings, biochemical detection, Western blot, and histological studies.ResultsPinocembrin treatment significantly attenuated the abnormality of heart rate variability (HRV), the prolongation of action potential duration (APD), the shortening of the effective refractory period (ERP), the reduction of transient outward potassium current (Ito), and the increase in L-type calcium current (ICa–L), which increase susceptibility to AF in a rat model of depression. Compared to the depressed rats, pinocembrin also increased the content of Kv4.2, Kv4.3, and atrial gap junction channel Cx40 and decreased the expression level of Cav1.2, which ameliorated oxidative stress and inhibited the ROS/p-p38MAPK pro-apoptotic pathway and the ROS/TGF-β1 pro-fibrotic pathway.ConclusionPinocembrin is a therapeutic strategy with great promise for the treatment of AF in depressed patients by reducing oxidative stress.

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Pinocembrin Decreases Ventricular Fibrillation Susceptibility in a Rat Model of Depression

Cited by 19 publications

References 47 publications

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus

Cardiac impact of high-frequency irreversible electroporation using an asymmetrical waveform on liver in vivo

Pinocembrin Decreases Atrial Fibrillation Susceptibility in a Rodent Model of Depression

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