Yaobi-Sutong formula modulates endothelial responses and MAPK1/NF-κB signaling in experimental inflammatory intervertebral disc injury

Background and objective Lumbar disc herniation (LDH) is a common cause of acute low back and radicular pain. Increasing evidence suggests that microvascular impairment and inflammation contribute to LDH-associated pain. Yaobi Sutong Formula (YSF), a traditional herbal prescription derived from Buyang Huanwu Decoction (BYHWD) and Wutou Decoction (WTD), may modulate inflammation-related responses, but its effects on endothelial dysfunction remain unclear. This study investigated the effects of YSF on inflammation-associated endothelial dysfunction and experimental intervertebral disc injury, with particular attention to MAPK1-related signaling. Methods The effects of YSF on Human umbilical vein endothelial cells (HUVECs) viability, migration, tube-like network formation, and MAPK1/NF-κB-related protein phosphorylation were evaluated in vitro. A rat model was established to assess histopathological alterations and vascular-associated marker expression following YSF treatment. Results YSF improved HUVEC viability, migration, and tube-like network formation under inflammatory conditions. Inflammatory stimulation reduced MAPK1 phosphorylation and increased NF-κB p65 phosphorylation, whereas YSF treatment partially reversed these changes in vitro and in vivo. YSF treatment was associated with improved histological appearance and increased CD31 and VEGFR2 immunoreactivity in the sampled endplate-adjacent tissues. MAPK1 knockdown or MEK inhibition with PD98059 attenuated the YSF-associated improvements in endothelial functional responses, suggesting possible involvement of MAPK1-related signaling. Conclusion YSF was associated with improved endothelial functional responses and attenuated histopathological alterations, accompanied by increased MAPK1 phosphorylation and reduced NF-κB p65 phosphorylation. These findings provide preliminary preclinical evidence supporting further investigation of YSF in inflammation-associated endothelial dysfunction and experimental intervertebral disc injury.