BACKGROUND In over 300 million clinical cases, antidepressant drugs seem to provide only symptomatic relief and limited protection in life-threatening depressive events. OBJECTIVES To compare neuronal-signaling mechanism and neuroprotective roles of Thymoquinone (TQ) suspension and its SLN (TQSLN) against standard antidepressant drug fluoxetine. METHODS This research investigated in-silico docking at NF-KB p50 active site, CLSM based gut permeation, screening of antidepressant activities and neurosignaling pathways involved. RESULTS As compared to fluoxetine, TQ reporteda significantly better docking score (-6.83 v/s -6.22) and a better lower free binding energy of (-34.715 Kcal/mol v/s -28.537 Kcal/mol). While poorly oral bioavailable and P-gp substrate TQ reported approximately 250% higher gut permeation if delivered as TQSLN formulation. In locomotor studies, as compared to TQS, TQSLN favored more prominent (p< 0.010) elevation in average time, horizontalactivity, average-velocity, and total-movement with reduced rest time LPS treated groups. However, in the tail suspension test, TQSLN significantly reduced immobility time (p<0.010). Similarly, In the modified force swimming test, TQSLN also significantly reduced immobility time (p<0.010), but swimming time (p<0.010) and climbing time (p<0.050) were significantly elevated. Subsequently, TQSLN reported significantly elevated neuroprotective BDNF (p<0.010) as well as hippocampal 5HT/TRP; accompanied with reduced levels of hippocampal inflammatory markers TNF-α (p<0.001) and IL-6 (p<0.010) as well as lower kynurenine and tryptophan ratio (KYN/TRP). Similarly, the hippocampal CA1 region further revealed TQSL more predominantly attenuated NF-kB nuclear translocation in the brain. CONCLUSION Despite the poor bioavailability of TQ, TQSLN potentially attenuates neuroinflammatory transmitters and favors BDNF to modulate depressive neurobehavioral states.

中文翻译：

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Thymoquinone Lipid Nanoparticles 通过神经保护性 BDNF 和下调 LPS 处理的大鼠中的神经炎症 NF-κB、IL-6 和 TNF-α 来切断抑郁症的痛处。

背景在超过 3 亿个临床病例中，抗抑郁药物似乎只能缓解症状，在危及生命的抑郁事件中提供有限的保护。目的比较百里醌 (TQ) 悬液及其前哨淋巴结 (TQSLN) 与标准抗抑郁药物氟西汀的神经元信号传导机制和神经保护作用。方法 本研究调查了 NF-KB p50 活性位点的计算机对接、基于 CLSM 的肠道渗透、抗抑郁活性的筛选和所涉及的神经信号通路。结果与氟西汀相比，TQ 报告了显着更好的对接分数（-6.83 v/s -6.22）和更好的较低自由结合能（-34.715 Kcal/mol v/s -28.537 Kcal/mol）。虽然口服生物利用度差和 P-gp 底物 TQ 报告说，如果作为 TQSLN 制剂递送，肠道渗透率大约高 250%。在运动研究中，与 TQS 相比，TQSLN 有利于平均时间、水平活动、平均速度和总运动的更显着 (p<0.010) 升高，同时减少休息时间 LPS 治疗组。然而，在悬尾试验中，TQSLN 显着减少了不动时间（p<0.010）。同样，在改良力量游泳测试中，TQSLN 也显着缩短了不动时间 (p<0.010)，但游泳时间 (p<0.010) 和攀爬时间 (p<0.050) 显着增加。随后，TQSLN 报告了显着升高的神经保护性 BDNF (p<0.010) 以及海马 5HT/TRP；伴随着海马炎症标志物 TNF-α (p<0.001) 和 IL-6 (p<0.010) 水平的降低以及犬尿氨酸和色氨酸比率 (KYN/TRP) 的降低。相似地，海马 CA1 区进一步揭示了 TQSL 更主要地减弱了大脑中的 NF-kB 核易位。结论 尽管 TQ 的生物利用度较差，但 TQSLN 可能会减弱神经炎症递质，并有利于 BDNF 调节抑郁性神经行为状态。