Neuroprotective effects of salidroside against cerebral ischemia-reperfusion injury involve downregulation of total NAMPT and suppression of microglial inflammation.
SAL may help mitigate the effects of cerebral ischemia-reperfusion injury by influencing NAMPT and inflammatory responses, but further research is needed to confirm these effects in humans.
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)-mediated neuroinflammation. SAL was administered at a dose of 10 μg/rat, and various neurological and inflammatory parameters were assessed. The results indicated significant changes in neurological deficits and inflammatory markers following SAL treatment.
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
Cerebral ischemia-reperfusion injury is a significant clinical concern, often leading to neuronal damage and inflammation. Previous research has indicated that NAMPT plays a role in neuroprotection, and salidroside has been suggested to have protective effects. This study aims to elucidate the mechanisms by which salidroside may confer neuroprotection, particularly through the modulation of NAMPT and microglial activity.
Methods
The study utilized a rodent model to assess the effects of salidroside on cerebral ischemia-reperfusion injury. Specific details regarding the population, sample size, dosage, duration, and primary or secondary outcome measures were not reported in the abstract.
Results
Not reported in abstract.
Interpretation
While the study addresses an important area of research, the lack of specific numeric findings limits the ability to compare these results to existing literature. Without clear effect sizes or statistical significance, it is difficult to assess the clinical relevance of the findings. The reliance on rodent models also raises questions about the applicability of the results to human subjects.
Key findings
- Not reported in abstract.
- Not reported in abstract.
- Not reported in abstract.
Limitations
- Not reported in abstract.
- Rodent model may not translate to humans.
- Specific numeric findings not provided.