Neuroprotective effects of salidroside against cerebral ischemia-reperfusion injury involve downregulation of total NAMPT and suppression of microglial inflammation.
SAL may have protective effects against cerebral ischemia-reperfusion injury in a rat model, but the clinical relevance of these findings to human patients is not established.
Where it sits
this study against the rest of the nad+ (nicotinamide adenine dinucleotide) corpusSummary and findings
This study investigated the effects of Salidroside (SAL) on cerebral ischemia-reperfusion (I/R) injury in male SD rats, focusing on its role in regulating nicotinamide phosphoribosyltransferase (NAMPT) and neuroinflammation. SAL was administered at a dose of 10 μg/rat, and various outcomes such as neurological deficit scores and infarct volume were measured. The results indicated significant changes in these parameters compared to controls.
Abstract
Objective This study investigated the protective effect of Salidroside (SAL) against cerebral ischemia-reperfusion (I/R) injury and its role in regulating nicotinamide phosphoribosyltransferase (NAMPT)-mediated neuroinflammation and damage. Methods In vivo, a middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in male SD rats. Animals were divided into sham-operated (Sham), I/R (MCAO-NS), MCAO+eNAMPT, and MCAO+eNAMPT+SAL groups. Recombinant NAMPT (5 μg/rat) and/or SAL (10 μg/rat) were administered intracerebroventricularly. Neurological deficit scores (mNSS), infarct volume (TTC), brain levels of IL-1β/TNF-α (ELISA), total NAMPT expression (WB/ELISA), and NAD+ content were assessed. In vitro, primary microglia were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and divided into control (Ctrl), OGD-NS, OGD+eNAMPT (20 ng/mL), and OGD+eNAMPT+SAL (6 μg/mL) groups. Cytotoxicity (LDH), viability (MTT), and IL-1β/TNF-α secretion (ELISA) were measured. Results Compared to Sham, the I/R group showed worsened neurological deficits, larger infarct volumes, elevated total NAMPT, TNF-α, and IL-1β levels (P < 0.001), and reduced NAD+ (P < 0.001). Exogenous eNAMPT further exacerbated these injuries and inflammation (P < 0.001). SAL treatment significantly reversed eNAMPT-aggravated neurological deficits and infarction (P < 0.001), downregulated total NAMPT, TNF-α, and IL-1β, and increased NAD+ levels (P < 0.001). In vitro, eNAMPT stimulation increased OGD/R-induced TNF-α and IL-1β secretion from microglia (P < 0.001), which SAL effectively inhibited (P < 0.001). Conclusion This study provides experimental evidence that the neuroprotective effects of SAL against cerebral I/R injury are associated with downregulation of pathologically elevated NAMPT expression (likely reflecting a reduction in pro-inflammatory eNAMPT), restoration of cerebral NAD+ homeostasis (potentially preserving iNAMPT function), and suppression of microglia-mediated neuroinflammation, suggesting that eNAMPT may serve as a potential effector molecule of SAL.
Background
The paper addresses the neuroprotective effects of salidroside in the context of cerebral ischemia-reperfusion injury, a condition known to provoke significant neuronal damage. Prior research has indicated that inflammation and metabolic dysregulation play critical roles in the pathophysiology of such injuries. Understanding the mechanisms by which salidroside may exert protective effects could contribute to the development of new therapeutic strategies.
Methods
The study employed a rodent model to assess the effects of salidroside on cerebral ischemia-reperfusion injury. Specific details regarding the sample size, dosing regimen, duration of treatment, and outcome measures were not reported in the abstract.
Results
Not reported in abstract.
Interpretation
Without specific numeric findings or effect sizes, it is challenging to compare these results to existing literature or assess their clinical significance. The reliance on rodent models introduces confounding factors that may limit the applicability of the findings to human populations. Caution is warranted in interpreting the implications for clinical practice.
Key findings
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Limitations
- Not reported in abstract.
- Rodent model may not translate to humans.
- Specific numeric findings not provided.
- No details on sample size or dosing regimen.