Safflower yellow alleviates sciatic nerve crush injury in rats: associated with TRPV1-pERK signaling pathway

Peripheral nerve injury (PNI) clinically resembles the traditional Chinese medical "Bi" and "Blood-Stasis" syndromes. Carthamus tinctorius L. (safflower) is a classic blood-activating and stasis-resolving herb commonly prescribed for PNI, whereas the protective effect of its major active component safflower yellow (SY) against PNI remains unclear.

To explore the efficacy and potential mechanisms of SY in ameliorating PNI using a rat sciatic nerve crush (SNC) model.

Rats were randomly assigned to four groups (n=10): Sham, SNC model, SNC+SY 20 mg/kg, and SNC+SY 40 mg/kg. All rats were sacrificed 15 days after SNC surgery.

SY intervention significantly promoted sciatic nerve functional recovery, alleviated mechanical allodynia, reversed denervation-induced gastrocnemius atrophy, and ameliorated histopathological damage in SNC-injured nerve tissues. Mechanistically, SY suppressed neuroinflammation, as evidenced by reduced CD68-positive macrophage accumulation and decreased levels of tumor necrosis factor-α, interleukin-1β, prostaglandin E₂, and cyclooxygenase-2, restored oxidative balance by regulating superoxide dismutase and malondialdehyde contents in injured nerves. Moreover, SY upregulated nerve regeneration markers (growth-associated protein 43, myelin basic protein, β₃-tubulin). Molecular docking revealed strong binding of SY to transient receptor potential vanilloid 1 (TRPV1) (-7.7 kcal/mol); molecular dynamics simulation verified stable complex formation (RMSD 0.38±0.03 nm). Biological validation demonstrated that SY markedly inhibited SNC-induced upregulation of TRPV1-pERK1/2 in sciatic nerve and dorsal root ganglion.

SY alleviates peripheral nerve damage, neuroinflammation, oxidative stress, promotes nerve repair in SNC rats, and is associated with modulation of TRPV1-pERK1/2 signaling, revealing a novel neuroprotective role of SY for PNI.