PMID: Curr Drug Metab. 2021 Nov 7. Epub 2021 Nov 7. PMID: 34749619 Abstract Title: Thymoquinone lipid nanoparticles cut the Gordian knots of depression via neuroprotective BDNF and downregulation of neuro-inflammatory NF-κB, IL-6, and TNF-α in LPS treated rats. Abstract: BACKGROUND: In over 300 million clinical cases, antidepressant drugs seem to provide only symptomatic relief and limited protection in life-threatening depressive events.OBJECTIVE: 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
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