摘要Oxaliplatin(OXA)is a widely used chemotherapeutic agent whose clinical utility is limited by OXA-induced peripheral neuropathy(OIPN).Sarco/endoplasmic reticulum Ca2+-ATPase(SERCA)transports Ca2+from the cytoplasm into the endoplasmic reticulum(ER),thereby maintaining intracellular Ca2+homeostasis.Schefflera kwangsiensis Merr.ex H.L.Li(SKM)is traditionally used to treat neuropathic pain conditions such as trigeminal neuralgia and sciat-ica,and its active component Schekwanglupaside C has been identified as a potent SERCA ac-tivator.In this study,an OIPN mouse model was established by intraperitoneal administra-tion of OXA(4 mg·kg-1)on days 1,2,8,9,15,and 16.SERCA2b mRNA and protein expression in dorsal root ganglia(DRG)were evaluated by quantitative polymerase chain reaction(qP-CR)and immunofluorescence.Mechanical allodynia was assessed using the Von Frey test.DRG neuronal excitability was examined by whole-cell current-clamp recordings,whereas ox-idative stress and neuronal apoptosis/necrosis were assessed using the reactive oxygen spe-cies(ROS)-sensitive probe 2',7'-dichlorofluorescin diacetate(H2DCFDA)and fluorescein iso-thiocyanate(FITC)/propidium iodide(PI)dual staining.This study identifies SERCA2b as a novel therapeutic target for OIPN.We observed that SERCA2b mRNA and protein levels were significantly downregulated during OIPN progression.Treatment with the SERCA agonist CDN1163(CDN),the ethyl acetate extract of SKM(SKM.Ext),or duloxetine(DLX)attenuated neuronal pathology,restored DRG neuron soma diameter,and reduced the expression of pro-inflammatory cytokines interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α).Pre-in-cubation of DRG neurons with CDN1163 or SKM.Ext for 1 h significantly attenuated OXA-in-duced hyperexcitability and reduced the abnormal increase in voltage-gated sodium channel(VGSC)current density.Inhibition of oxidative stress with N-acetyl-L-cysteine(NAC)signific-antly restored SERCA expression in OIPN,indicating that oxidative stress downregulates SERCA2b in DRG.Collectively,these findings demonstrate that activation of SERCA2b by CDN1163 or Schefflera kwangsiensis extract enhances SERCA2b expression,reduces DRG neuronal sensitization,and alleviates OIPN.This work supports SERCA2b as a novel thera-peutic target for OXA-induced neuropathy and expands the potential clinical analgesic indica-tions of Schefflera kwangsiensis.