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Panax notoginseng saponins ameliorate spinal cord injury by inhibiting JAK2/STAT3-mediated macrophage polarization: Enhanced delivery by ultrasound-targeted microbubble destruction

Year: 2026

Type: article

Abstract: • PNS alleviates spinal cord injury by inhibiting macrophage M1 polarization, promoting M2 polarization, and thereby reducing neuronal apoptosis. • PNS modulates macrophage polarization by inhibiting the JAK2/STAT3 signaling pathway. • UTMD strengthens PNS’s regulatory effects on macrophage polarization and the JAK2/STAT3 pathway. Spinal cord injury (SCI) causes abnormal macrophage polarization, worsening inflammation and neuronal apoptosis, with current therapies showing limited efficacy. Panax Notoginseng Saponins (PNS) has anti-inflammatory and neuroprotective potential but is limited by low bioavailability. Ultrasound-targeted microbubble destruction (UTMD) can open the blood-spinal cord barrier to improve drug delivery. To clarify the role of PNS and molecular mechanisms in regulating macrophage polarization for SCI and explore the effect of UTMD on enhancing PNS efficacy. RAW264.7 macrophages and rat SCI models were used. Flow cytometry, RT-qPCR, Western blotting (WB), TUNEL staining, BBB scoring, and MRI were applied to detect polarization markers, JAK2/STAT3 pathway proteins, neuronal apoptosis, and neurological recovery. PNS dose-dependently promoted macrophage M2 polarization, inhibited the JAK2/STAT3 pathway, and reduced neuronal apoptosis. These effects were enhanced by the JAK2/STAT3 inhibitor AG490, while PNS also antagonized the pro-apoptotic action of the pathway activator colivelin. UTMD strengthened PNS’s effects in vitro. In rats, compared with the SCI-only group, the SCI+PNS group already showed therapeutic effects, with improved BBB scores, less M1 infiltration, suppressed JAK2/STAT3, and reduced apoptosis and cyst areas. Notably, the SCI+UTMD+PNS group exhibited even more pronounced improvements in these aspects and superior efficacy to both the SCI and SCI+PNS groups. PNS inhibits JAK2/STAT3 to promote M2 polarization and reduce apoptosis. UTMD amplifies PNS’s efficacy, providing a novel SCI therapy strategy. PNS inhibits the JAK2/STAT3 pathway to promote macrophage M2 polarization and reduce neuronal apoptosis, while UTMD amplifies the therapeutic efficacy of PNS.

Source: Phytomedicine

DOI: 10.1016/j.phymed.2026.157856