Neurochemistry international最新文献_第3页

Vagus nerve stimulation with a small total charge transfer improves motor behavior and reduces neuroinflammation in a mouse model of Parkinson's disease 在帕金森病小鼠模型中，通过少量总电荷转移刺激迷走神经可改善运动行为并减轻神经炎症。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-10-01 DOI: 10.1016/j.neuint.2024.105871

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Conventional treatments are ineffective in reversing disease progression. Recently, the therapeutic and rehabilitation potential of vagus nerve stimulation (VNS) in PD has been explored. However, the underlying mechanisms remain largely unknown. In this study, we investigated the neuroprotective effects of VNS in a lateral lesioned mice model of PD. Excluding controls, experimental mice received cuff electrode implantation on the left vagus nerve and 6-hydroxydopamine administration into the bilateral striatum. After ten days, electrical stimulation was delivered for 11 consecutive days onto PD animals. Behavioral tests were performed after stimulation. The expression of TH, Iba-1, GFAP, adrenergic receptors and cytokines in the SN and striatum was detected by immunofluorescence or western blotting. The activity of noradrenergic neurons in the locus coeruleus (LC) was also measured. Our results suggest that VNS improved behavioral performance in rod rotation, open field tests and pole-climbing tests in PD mice, accompanied by a decrease in the loss of dopaminergic neurons in the SN and increased TH expression in the striatum. Neuroinflammation-related factors, such as GFAP, Iba-1, TNF-α and IL-1β were also suppressed in PD mice after VNS compared to those without treatment. Furthermore, the proportion of c-Fos-positive noradrenergic neurons in the LC increased when animals received VNS. Additionally, the expression of the adrenergic receptor of α1BR was also upregulated after VNS compared to PD mice. In conclusion, VNS has potential as a novel PD therapy for neuroprotective effects, and indicate that activation of norepinephric neurons in LC may plays an important role in VNS treatment for PD.

帕金森病（PD）是一种常见的神经退行性疾病，其特征是黑质（SN）中多巴胺能（DA）神经元的丧失。传统治疗方法无法有效逆转疾病的进展。最近，迷走神经刺激（VNS）对帕金森病的治疗和康复潜力得到了探索。然而，其潜在机制在很大程度上仍不为人所知。在本研究中，我们研究了迷走神经刺激在侧支损伤型帕金森病小鼠模型中的神经保护作用。除去对照组，实验小鼠接受了左侧迷走神经袖带电极植入和双侧纹状体 6-羟基多巴胺给药。十天后，对帕金森病动物进行连续11天的电刺激。刺激后进行行为测试。免疫荧光或 Western 印迹法检测了神经元和纹状体中 TH、Iba-1、GFAP、肾上腺素能受体和细胞因子的表达。此外，还测量了脑室（LC）中去甲肾上腺素能神经元的活性。我们的结果表明，VNS 改善了帕金森病小鼠在杆旋转、开阔地测试和爬杆测试中的行为表现，同时减少了SN中多巴胺能神经元的丢失，增加了纹状体中TH的表达。与未接受治疗的小鼠相比，VNS治疗后PD小鼠的神经炎症相关因子，如GFAP、Iba-1、TNF-α和IL-1β也受到抑制。此外，接受 VNS 治疗的小鼠 LC 中 c-Fos 阳性的去肾上腺素能神经元比例增加。此外，与帕金森病小鼠相比，VNS治疗后α1BR肾上腺素能受体的表达也上调了。总之，VNS 有可能成为一种新型的 PD 治疗方法，具有神经保护作用，并表明激活 LC 中的去甲肾上腺素能神经元可能在 VNS 治疗 PD 中发挥重要作用。

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引用次数: 0

Honokiol-induced SIRT3 upregulation protects hippocampal neurons by suppressing inflammatory processes in pilocarpine-induced status epilepticus Honokiol诱导的SIRT3上调可抑制皮质类药物诱发的癫痫状态的炎症过程，从而保护海马神经元。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-10-01 DOI: 10.1016/j.neuint.2024.105873

Status epilepticus (SE), a continuous and self-sustaining epileptic seizure lasting more than 30 min, is a neurological emergency that can cause severe brain injuries and increase the risk for the development of epilepsy. Over the past few decades, accumulating evidence has suggested the importance of brain inflammation in the pathogenesis of epilepsy. Honokiol (HNK), a pharmacological activator of sirtuin 3 (SIRT3), is a bioactive compound extracted from the bark or leaves of Magnolia plants that possesses therapeutic benefits for preventing the development of inflammatory injury. However, the therapeutic effects of HNK against epileptic brain injury via regulating molecular mechanisms related to neuroinflammation remains elusive. Therefore, the present study investigated the effects of HNK on pilocarpine-induced status epilepticus (PCSE) and the therapeutic benefits of HNK in regulating inflammatory processes in the hippocampus. Treatment with HNK before PCSE induction attenuated the initiation of behavioral seizures. Post-treatment with HNK after SE onset increased SIRT3 expression, which mitigated glial activation, including reactive astrocytes and activated microglia, in the hippocampus following PCSE. Moreover, HNK treatment reduced the activation of the nuclear factor-κB/nucleotide-binding domain leucine-rich repeat with a pyrin-domain containing 3 inflammasome pathway, thereby inhibiting the production of interleukin-1β pro-inflammatory cytokine, subsequently alleviating PCSE-triggered apoptotic neuronal death in the hippocampus. These results indicate that HNK-induced SIRT3 upregulation has the potential to prevent the progression of epileptic neuropathology through its anti-inflammatory properties. Therefore, the present study suggests that HNK is a natural therapeutic agent for epileptic brain injury.

癫痫状态（SE）是一种持续时间超过 30 分钟的连续性、自我维持性癫痫发作，是一种神经系统急症，可导致严重的脑损伤并增加癫痫的发病风险。过去几十年来，越来越多的证据表明脑部炎症在癫痫发病机制中的重要性。Honokiol（HNK）是sirtuin 3（SIRT3）的药理激活剂，是从厚朴植物的树皮或叶子中提取的一种生物活性化合物，具有预防炎症损伤发展的治疗功效。然而，HNK 通过调节与神经炎症相关的分子机制对癫痫性脑损伤的治疗效果仍不明确。因此，本研究探讨了 HNK 对皮质类固醇诱发的癫痫状态（PCSE）的影响，以及 HNK 在调节海马炎症过程中的治疗作用。在 PCSE 诱导前用 HNK 治疗可减轻行为性癫痫发作的开始。在癫痫发作开始后使用 HNK 治疗可增加 SIRT3 的表达，从而减轻 PCSE 后海马神经胶质的活化，包括反应性星形胶质细胞和活化的小胶质细胞。此外，HNK 治疗减少了核因子-κB/核苷酸结合域富含亮氨酸重复序列的含吡啶域 3 炎性体通路的激活，从而抑制了白细胞介素-1β 促炎细胞因子的产生，随后缓解了 PCSE 在海马中触发的神经元凋亡。这些结果表明，HNK 诱导的 SIRT3 上调有可能通过其抗炎特性阻止癫痫神经病理学的发展。因此，本研究表明 HNK 是一种治疗癫痫性脑损伤的天然药物。

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引用次数: 0

Bacopa monnieri confers neuroprotection by influencing signaling pathways associated with interleukin 4, 13 and extracellular matrix organization in Alzheimer's disease: A proteomics-based perspective 猴面包树通过影响与白细胞介素 4、13 和阿尔茨海默病细胞外基质组织相关的信号通路来提供神经保护：基于蛋白质组学的视角

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-09-29 DOI: 10.1016/j.neuint.2024.105864

Alzheimer's disease, a prevalent neurodegenerative disorder in the elderly, is characterized by the accumulation of senile plaques and neurofibrillary tangles, triggering oxidative stress, neuroinflammation, and neuronal apoptosis. Current therapies focus on symptomatic treatment rather than targeting the underlying disease-modifying molecular mechanisms and are often associated with significant side effects. Bacopa monnieri, a traditional Indian herb with nootropic properties, has shown promise in neurological disorder treatment from ancient times. However, its mechanisms of action in Alzheimer's disease remain elusive. In this study, a cellular model for Alzheimer's disease was created by treating differentiated IMR-32 cells with beta-amyloid, 1–42 peptide (Aβ₄₂). Additionally, a recovery model was established through co-treatment with Bacopa monnieri to explore its protective mechanism. Co-treatment with Bacopa monnieri extract recovered Aβ₄₂ induced damage as evidenced by the decreased apoptosis and reduced reactive oxygen species production. Mass spectrometry-based quantitative proteomic analysis identified 21,674 peptides, corresponding to 3626 proteins from the Alzheimer's disease model. The proteins dysregulated by Aβ₄₂ were implicated in cellular functions, such as negative regulation of cell proliferation and microtubule cytoskeleton organization. The enriched pathways include extracellular matrix organization and interleukin-4 and interleukin-13 signaling. Bacopa monnieri co-treatment showed remarkable restoration of Aβ₄₂ altered proteins, including FOSL1, and TDO2. The protein-protein interaction network analysis of Bacopa monnieri restored proteins identified the hub gene involved in Alzheimer's disease. The findings from this study may open up new avenues for creating innovative therapeutic approaches for Alzheimer's disease.

阿尔茨海默病是一种普遍存在于老年人中的神经退行性疾病，其特征是老年斑和神经纤维缠结的累积，引发氧化应激、神经炎症和神经元凋亡。目前的疗法侧重于对症治疗，而不是针对潜在的疾病改变分子机制，而且往往会产生严重的副作用。百服宁（Bacopa monnieri）是一种传统的印度草药，具有神经营养特性，自古以来就显示出治疗神经系统疾病的前景。然而，它在阿尔茨海默病中的作用机制仍然难以捉摸。在这项研究中，通过用β-淀粉样蛋白1-42肽（Aβ42）处理分化的IMR-32细胞，建立了阿尔茨海默病的细胞模型。此外，还通过与百忧解联合处理建立了一个恢复模型，以探索其保护机制。通过减少细胞凋亡和活性氧的产生，联合使用百服宁提取物可恢复 Aβ42 诱导的损伤。基于质谱的定量蛋白质组分析鉴定出了 21674 个肽段，对应于阿尔茨海默病模型中的 3626 个蛋白质。Aβ42调控失调的蛋白质与细胞功能有关，如细胞增殖负调控和微管细胞骨架组织。富集的途径包括细胞外基质组织以及白细胞介素-4和白细胞介素-13信号转导。百服宁联合治疗显示，Aβ42改变的蛋白质，包括FOSL1和TDO2，得到了显著的恢复。通过对单叶枯草恢复蛋白的蛋白-蛋白相互作用网络分析，确定了阿尔茨海默病的枢纽基因。这项研究的发现可能会为阿尔茨海默病的创新治疗方法开辟新的途径。

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引用次数: 0

Unraveling the role of cholecystokinin in epilepsy: Mechanistic insight into neuroplasticity 揭示胆囊收缩素在癫痫中的作用：神经可塑性的机制启示。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-09-28 DOI: 10.1016/j.neuint.2024.105870

Epilepsy is a disorder characterized by an imbalance between excitability and inhibition, leading to uncontrolled hyperexcitability of neurons in the central nervous system. Despite the prevalence of epileptic seizures, the underlying mechanisms driving this hyperexcitability remain poorly understood. This review article aims to enhance our understanding of the mechanisms of epilepsy, with a specific focus on the role of cholecystokinin (CCK) in this debilitating disease. We will begin with an introduction to the topic, followed by an examination of the role of GABAergic neurons and the synaptic plasticity mechanisms associated with seizures. As we delve deeper, we will elucidate how CCK and its receptors contribute to seizure behavior. Finally, we will discuss the CCK-dependent synaptic plasticity mechanisms and highlight their potential implications in seizure activity. Through a comprehensive examination of these aspects, this review provides valuable insights into the involvement of CCK and its receptors in epilepsy. By improving our understanding of the mechanisms underlying this condition, particularly the role of CCK, we aim to contribute to the development of more effective treatment strategies.

癫痫是一种以兴奋性和抑制性失衡为特征的疾病，会导致中枢神经系统的神经元出现不受控制的过度兴奋。尽管癫痫发作十分普遍，但人们对这种过度兴奋的内在机制仍然知之甚少。这篇综述文章旨在加深我们对癫痫机制的了解，并特别关注胆囊收缩素（CCK）在这一使人衰弱的疾病中的作用。我们将首先介绍这一主题，然后探讨 GABA 能神经元的作用以及与癫痫发作相关的突触可塑性机制。随着研究的深入，我们将阐明 CCK 及其受体如何对癫痫发作行为产生影响。最后，我们将讨论依赖 CCK 的突触可塑性机制，并强调其在癫痫发作活动中的潜在影响。通过对这些方面的全面研究，本综述为了解 CCK 及其受体在癫痫中的作用提供了宝贵的见解。我们希望通过加深对癫痫发病机制的了解，特别是对CCK作用的了解，为制定更有效的治疗策略做出贡献。

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引用次数: 0

Neuroprotective effects of Withania somnifera on ischemic stroke are mediated via anti-inflammatory response and modulation of neurotransmitter levels 睡茄对缺血性中风的神经保护作用是通过抗炎反应和调节神经递质水平来实现的。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-09-28 DOI: 10.1016/j.neuint.2024.105867

The present study was designed to evaluate the beneficial effects of hydroalcoholic root extract of Withania somnifera (WS) on ischemia-reperfusion injury (IRI) induced by Middle Cerebral Artery Occlusion (MCAO). MCAO animals showed increase in IL-6, TNF-α and MCP-1 levels in terms of mRNA and protein levels. Concomitantly, mRNA and protein levels for astrocyte and microglial activation markers; GFAP and IBA-1, were increased in MCAO animals. COX-2 and NF-kβ protein levels were also increased in the brains of MCAO animals. The levels of neurotransmitters; glutamate and GABA were increased in the MCAO animals. On the contrary, levels of catecholamines; dopamine, norepinephrine and serotonin were reduced in the MCAO animals. Additionally, MCAO animals showed reduced locomotor activity. However, pre-supplementation with WS hydro-alcoholic root extract at a dose of 300 mg/kg, body weight to MCAO animals reduced the expression of IL-6, TNF-α and MCP-1. In addition, WS also reduced the number of GFAP and Iba-1 positive cells in comparison to MCAO animals. WS pre-supplementation was also observed to inhibit MCAO induced increase in COX-2; NF-kβ proteins and reduce the glutamate levels. The levels of GABA, dopamine, norepinephrine and serotonin were increased in WS pre-supplemented MCAO animals. WS pre-supplementation also prevented motor deficits in the MCAO animals. Taken together, these findings suggest that WS is effective in attenuating IRI induced neuroinflammation, neurochemical alterations and motor deficits in MCAO model of ischemic stroke thereby suggesting its ameliorative role in ischemia-reperfusion injury.

本研究旨在评估薇甘菊（WS）水醇根提取物对大脑中动脉闭塞（MCAO）诱导的缺血再灌注损伤（IRI）的有益作用。MCAO 动物的 mRNA 和蛋白水平显示 IL-6、TNF-α 和 MCP-1 水平升高。同时，MCAO动物的星形胶质细胞和小胶质细胞活化标记物（GFAP和IBA-1）的mRNA和蛋白质水平也有所升高。MCAO动物大脑中的COX-2和NF-kβ蛋白水平也有所增加。神经递质谷氨酸和 GABA 的水平在 MCAO 动物中有所增加。相反，MCAO 动物体内儿茶酚胺、多巴胺、去甲肾上腺素和血清素的水平降低。此外，MCAO 动物的运动活动减少。然而，在 MCAO 动物体内预先补充 300 毫克/千克（体重）剂量的 WS 水醇根提取物可减少 IL-6、TNF-α 和 MCP-1 的表达。此外，与 MCAO 动物相比，WS 还能减少 GFAP 和 Iba-1 阳性细胞的数量。观察还发现，预先补充 WS 可抑制 MCAO 诱导的 COX-2、NF-kβ 蛋白的增加，并降低谷氨酸的水平。在预先补充 WS 的 MCAO 动物中，GABA、多巴胺、去甲肾上腺素和血清素的水平均有所提高。预先补充 WS 还能防止 MCAO 动物出现运动障碍。综上所述，这些研究结果表明，WS 能有效减轻 IRI 诱导的神经炎症、神经化学物质改变和缺血性中风 MCAO 模型的运动障碍，从而表明其在缺血再灌注损伤中的改善作用。

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引用次数: 0

Phyto-nanotechnology: A novel beneficial strategy for Alzheimer's disease therapy 植物纳米技术：一种治疗阿尔茨海默病的新型有益策略。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-09-25 DOI: 10.1016/j.neuint.2024.105868

Alzheimer's disease, a neurodegenerative condition, is characterized by the slow and progressive deterioration of the cognitive functions of geriatric patients. It occurs due to exacerbation of neurons in the brain, indicated by loss of memory, mood instability, and even death. The aggregation of amyloid β protein and neurofibrillary tangles-atypical forms of tau protein is the major cause of this disease. Phytoconstituents have been frequently employed in treating Alzheimer's disease. These natural compounds act through different molecular mechanisms to treat the disease. However, their potential in Alzheimer's disease therapy may be limited due to poor blood-brain barrier permeability, off-target effects, low bioavailability, etc. In recent times, nanotechnology has gained attraction to overcome these challenges. This article focuses on the potential phytoconstituents for Alzheimer's disease treatment and the associated limitations. Moreover, it highlights various nanoformulation strategies employed to penetrate the blood-brain barrier effectively, avoid side effects, improve bioavailability, and target specificity in treating Alzheimer's disease. The integration of nanotechnology with plant-derived compounds has the potential to revolutionize the therapeutic landscape for Alzheimer's disease.

阿尔茨海默病是一种神经退行性疾病，其特征是老年患者的认知功能缓慢而逐渐地退化。它的发生是由于大脑神经元的恶化，表现为记忆力减退、情绪不稳定，甚至死亡。淀粉样β蛋白和神经纤维缠结（tau蛋白的典型形式）的聚集是这种疾病的主要原因。植物成分经常被用于治疗阿尔茨海默病。这些天然化合物通过不同的分子机制来治疗这种疾病。然而，由于血脑屏障渗透性差、脱靶效应、生物利用度低等原因，它们在阿尔茨海默病治疗中的潜力可能受到限制。近来，纳米技术在克服这些挑战方面越来越有吸引力。本文重点介绍了治疗阿尔茨海默病的潜在植物成分及其相关局限性。此外，文章还重点介绍了各种纳米制剂策略，以有效穿透血脑屏障、避免副作用、提高生物利用度和治疗阿尔茨海默病的靶向特异性。纳米技术与植物提取化合物的结合有望彻底改变阿尔茨海默病的治疗格局。

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引用次数: 0

Neuroprotective effect of vitamin B12 supplementation on cognitive functions and neuronal morphology at different time intervals after traumatic brain injury in male Swiss albino mice 补充维生素 B12 对雄性瑞士白化小鼠脑外伤后不同时间间隔认知功能和神经元形态的神经保护作用

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-09-25 DOI: 10.1016/j.neuint.2024.105869

Traumatic brain injury is a highly irreversible process that consists of primary as well as secondary injury which develops and progresses over months to years, leading to cognitive dysfunctions. Vitamin B₁₂ received considerable interest due to its potential therapeutic properties. The pathways of vitamin B₁₂ are closely related to neuronal survival but its effects on the pathophysiology of injury with respect to cognition is a relatively unexplored area of research. In this study, we investigated, the effect of vitamin B₁₂ and its involvement in neuroprotection on TBI-induced pathophysiology in male Swiss albino mice. Our findings suggested that vitamin B₁₂ supplementation improves TBI-mediated neurological impairments, spatial and recognition memory, and anxiety-like behavior. Furthermore, the oxidative stress was reduced by declined homocysteine level with vitamin B₁₂ supplementation validating declined expression of astrocytes and TBI biomarkers. The studies on neuronal morphology revealed that vitamin B₁₂ supplementation increases the dendritic arborization and density of mushroom and filopodia-shaped spines and further increases the expression of synaptic plasticity-related genes and proteins. Taken together, our findings reveal that, supplementation of vitamin B₁₂ restored the TBI-induced downregulation of dendritic arborization, and spine density which ultimately increases synaptic plasticity, cell survival, and recovery of cognitive dysfunctions.

创伤性脑损伤是一个高度不可逆的过程，包括原发性和继发性损伤，经过数月至数年的发展和演变，导致认知功能障碍。维生素 B12 因其潜在的治疗特性而备受关注。维生素 B12 的作用途径与神经元的存活密切相关，但其对认知损伤的病理生理学的影响是一个相对尚未开发的研究领域。在这项研究中，我们调查了维生素 B12 及其参与神经保护对雄性瑞士白化小鼠创伤性脑损伤引起的病理生理学的影响。我们的研究结果表明，补充维生素 B12 可改善创伤性脑损伤引起的神经损伤、空间记忆和识别记忆以及焦虑行为。此外，补充维生素 B12 后，同型半胱氨酸水平下降，氧化应激也随之减少，这验证了星形胶质细胞和创伤性脑损伤生物标志物表达的下降。对神经元形态学的研究表明，补充维生素 B12 可增加树突轴化以及蘑菇状和丝状棘突的密度，并进一步增加突触可塑性相关基因和蛋白的表达。综上所述，我们的研究结果表明，补充维生素 B12 可恢复创伤性脑损伤引起的树突轴化和棘突密度下调，从而最终提高突触可塑性、细胞存活率和认知功能障碍的恢复。

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引用次数: 0

Statins ameliorate oxaliplatin- and paclitaxel-induced peripheral neuropathy via glutathione S-transferase 他汀类药物通过谷胱甘肽-S-转移酶改善奥沙利铂和紫杉醇诱发的周围神经病变

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-09-21 DOI: 10.1016/j.neuint.2024.105863

Some therapeutic agents have been found to have effects beyond their primary indications. Peripheral neuropathy, a common side effect of chemotherapy, remains inadequately treated. Identifying additional properties of existing medications could thus uncover novel therapeutic avenues. Previous studies have identified an additional effect of simvastatin in reducing neuropathy; however, the mechanism underlying this effect remains unclear. We investigated the novel effects of statins on chemotherapy-induced peripheral neuropathy in mice. Mice treated with oxaliplatin or paclitaxel did not show exacerbation or improvement in cold sensations upon acetone testing with statin administration. However, concurrent oral statin treatment mitigated the nociceptive response to mechanical stimuli induced by each anti-tumor agent. Co-administration of a glutathione S-transferase inhibitor, which modulates redox reactions, abolished the ameliorative effect of statins on mechanical nociceptive behavior. Additionally, the glutathione S-transferase inhibitor did not affect normal sensory perception or impair the anti-tumor effect of chemotherapy agents. A search for GST-associated molecules and pathways using artificial intelligence revealed that GST regulates inflammatory cytokines as a regulatory or causative gene. Our findings suggest that statins have class effects that ameliorate cytotoxic anti-cancer drug-induced mechanical allodynia via GST pathway activation.

一些治疗药物被发现具有超出其主要适应症的效果。周围神经病变是化疗的一种常见副作用，但治疗效果不佳。因此，识别现有药物的其他特性可以发现新的治疗途径。先前的研究发现辛伐他汀具有减轻神经病变的额外作用，但这种作用的机制仍不清楚。我们研究了他汀类药物对化疗引起的小鼠周围神经病变的新作用。接受奥沙利铂或紫杉醇治疗的小鼠在服用他汀类药物进行丙酮测试时，冷感没有出现加剧或改善。不过，同时口服他汀类药物可减轻每种抗肿瘤药物诱发的机械刺激痛觉反应。同时服用谷胱甘肽-S-转移酶抑制剂（可调节氧化还原反应）可消除他汀类药物对机械痛觉行为的改善作用。此外，谷胱甘肽-S-转移酶抑制剂不会影响正常的感官知觉，也不会损害化疗药物的抗肿瘤作用。利用人工智能搜索谷胱甘肽相关分子和通路发现，谷胱甘肽作为调节基因或致病基因调节炎症细胞因子。我们的研究结果表明，他汀类药物具有类药物效应，可通过激活 GST 通路改善细胞毒性抗癌药物诱导的机械异感。

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引用次数: 0

Role of Mandukparni (Centella asiatica Linn Urban) in neurological disorders: Evidence from ethnopharmacology and clinical studies to network enrichment analysis Mandukparni (Centella asiatica Linn Urban) 在神经系统疾病中的作用：从民族药理学和临床研究到网络富集分析的证据。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-09-20 DOI: 10.1016/j.neuint.2024.105865

Centella asiatica Linn Urban (C. asiatica), aka Mandukparni, is one of the flagship herbs used in traditional medicines to effectively manage neurological problems. Although this plant has a wealth of comprehensive preclinical pharmacological profiles, further clinical research and execution of its molecular mode of action are still required. We searched electronic databases (Google Scholar, SciFinder, MEDLINE, Scopus, EMBASE, Science Direct, and PubMed) using relevant key words to retrieve information pertaining to C. asiatica till June 2023 and performed network pharmacology to understand the mechanism related to their neurobiological roles. This study extensively analyses its pharmacological properties, nutritional profile, ethnomedical uses, safety, and mechanistic role in treating neurological and neurodegenerative disorders. Additionally, a network pharmacology study was performed which suggests that its phytomolecules are involved in different neuroactive ligand-receptor pathways, glial cell differentiation, gliogenesis, and astrocyte differentiation. Hopefully, this report will lead to a paradigm shift in medical practice, research, and the creation of phytopharmaceuticals derived from C. asiatica that target the central nervous system.

积雪草（Centella asiatica Linn Urban），又名曼杜克帕尼（Mandukparni），是传统医学中用于有效治疗神经问题的主要草药之一。虽然这种植物拥有丰富全面的临床前药理特征，但仍需要进一步的临床研究并确定其分子作用模式。我们使用相关关键词搜索了电子数据库（Google Scholar、SciFinder、MEDLINE、Scopus、EMBASE、Science Direct 和 PubMed），检索了截至 2023 年 6 月有关茜草的信息，并进行了网络药理学研究，以了解其神经生物学作用的相关机制。本研究广泛分析了其药理特性、营养成分、民族医药用途、安全性以及在治疗神经和神经退行性疾病中的作用机制。此外，还进行了一项网络药理学研究，表明其植物大分子参与了不同的神经活性配体-受体通路、神经胶质细胞分化、神经胶质细胞生成和星形胶质细胞分化。希望本报告能促使医学实践、研究和针对中枢神经系统的茜草提取物植物药的开发发生范式转变。

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引用次数: 0

Cycloleucine induces neural tube defects by reducing Pax3 expression and impairing the balance of proliferation and apoptosis in early neurulation 环亮氨酸会降低 Pax3 的表达，并损害早期神经形成过程中增殖和凋亡的平衡，从而诱发神经管缺陷。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international

Pub Date : 2024-09-20 DOI: 10.1016/j.neuint.2024.105861

S-adenosylmethionine (SAM) plays a critical role in the development of neural tube defects (NTDs). Studies have shown that the paired box 3 (Pax3) gene is involved in neural tube closure. However, the exact mechanism between Pax3 and NTDs induced by SAM deficiency remains unclear. Here, The NTD mouse model was induced using cycloleucine (CL), an inhibitor of SAM biosynthesis, to determine the effect of Pax3 on NTDs. The effect of CL on NTD occurrence was assessed by 5-ethynyl-2′-deoxyuridine (EdU) staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and Western blot in NTD embryonic brain tissues and immortalized hippocampal neuron cells (HT-22). A high incidence of NTDs was observed when CL was administered at a dose of 200 mg/kg body weight. The levels of SAM and Pax3 were significantly reduced in NTD embryonic brain tissues and HT-22 cells after CL exposure. Decreased proliferation and excessive apoptosis were observed in neuroepithelial cells of NTD embryos and HT-22 cells under SAM deficiency, but these effects were reversed by overexpression of Pax3. These results suggest that decreased expression of Pax3 impairs the dynamic balance between cellular proliferation and apoptosis, contributing to NTDs induced by SAM deficiency, which would provide new insights for clarifying the underlying mechanism of NTDs.

S- 腺苷蛋氨酸（SAM）在神经管畸形（NTD）的发育过程中起着至关重要的作用。研究表明，配对盒 3（Pax3）基因参与了神经管闭合。然而，Pax3与SAM缺乏诱导的NTD之间的确切机制仍不清楚。在此，我们使用SAM生物合成抑制剂环亮氨酸（CL）诱导了NTD小鼠模型，以确定Pax3对NTD的影响。在NTD胚胎脑组织和永生化海马神经元细胞（HT-22）中，通过5-乙炔基-2'-脱氧尿苷（EdU）染色、免疫组化、末端脱氧核苷酸转移酶介导的dUTP缺口标记（TUNEL）、实时定量反转录聚合酶链反应（qRT-PCR）和Western印迹等方法评估了CL对NTD发生的影响。当 CL 的剂量为 200 毫克/千克体重时，NTD 的发生率很高。接触 CL 后，NTD 胚胎脑组织和 HT-22 细胞中的 SAM 和 Pax3 水平显著降低。在 SAM 缺乏的情况下，NTD 胚胎和 HT-22 细胞的神经上皮细胞出现增殖减少和过度凋亡，但过表达 Pax3 可逆转这些影响。这些结果表明，Pax3表达减少会破坏细胞增殖和凋亡之间的动态平衡，从而导致SAM缺乏诱导的NTD，这将为阐明NTD的内在机制提供新的见解。

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