Protective Effects of Safranal Against Spike Protein-Induced Mitochondrial Dysfunction and Inflammation in Peripheral and Central Immune Cells
Bibliographic record
Abstract
Background: .) contains bioactive molecules with antioxidant, anti-inflammatory, and neuroprotective properties. Growing evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes neuroinflammation and mitochondrial dysfunction contributing to neuro-coronavirus disease. Objectives: The aim of this study is to evaluate the antioxidant, anti-inflammatory, and neuroprotective effects of 3 saffron derivatives, picrocrocin, 4-hydroxysafranal, and safranal, in peripheral immune cells and microglia, and to test the hypothesis that these compounds, especially safranal, counteract Spike protein 1(S1)-induced inflammation and mitochondrial dysfunction. Methods: An immortalized murine microglial cell line (BV2) and human peripheral blood mononuclear cells (PBMCs) from healthy donors were treated with saffron derivatives at nontoxic concentrations (0.05-0.5 mM). Cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-5-(3‑carboxymethoxyphenyl)-2-(4‑sulfophenyl)-2H‑tetrazolium (MTS) assay), antioxidant capacity [2,2-diphenyl-1-picrylhydrazyl (DPPH)], intracellular reactive oxygen species (ROS; 2,7-dichlorodihydrofluorescein diacetate), cytokine expression (enzyme-linked immunosorbent assay and quantitative polymerase chain reaction), and mitochondrial membrane potential (5,5',6,6'‑tetrachloro‑1,1',3,3'‑tetraethylbenzimidazolylcarbocyanine iodide (JC-1) assay) were assessed. Lipopolysaccharide (LPS) served as an inflammatory control, whereas S1 was used to model SARS-CoV-2-mediated neuroinflammation and mitochondrial damage. Results: All saffron derivatives showed antioxidant activity, with safranal demonstrating the strongest DPPH radical scavenging effect and the most pronounced reduction of intracellular ROS. In LPS-stimulated BV2 cells, safranal significantly decreased inducible nitric oxide synthase expression. In PBMCs, saffron compounds attenuated LPS-induced interleukin-1 beta (IL-1β) release, with safranal showing the greatest decrease. S1 increased IL-1β and tumor necrosis factor-alpha expression in BV2 microglia. Co-treatment with safranal reduced these cytokines by ∼38% and 44%, respectively. S1 induced a loss of mitochondrial membrane potential, which was effectively restored by safranal, as confirmed by JC-1 fluorescence analysis. Conclusions: These findings identify safranal as a promising neuroprotective candidate for preventing or mitigating SARS-CoV-2-associated neurological damage and other disorders involving microglial activation and mitochondrial impairment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".