Protective Effect of Inula britannica Flower Extract on Corticosterone-Induced PC12 Cells via Regulation of Stress-Related Factors

The flowers of Inula britannica var. japonica (Asteraceae) has been listed in the Korean Herbal Pharmacopoeia as a medicinal herb used to alleviate cough, phlegm, and gastrointestinal discomfort. Traditionally, it has been prescribed for inflammatory disorders such as bronchitis, as well as for metabolic diseases including diabetes and hypertension. Recent pharmacological studies have validated its traditional uses and revealed novel bioactivities such as anti-inflammatory, antioxidant, anti-obesity, and neuroprotective effects, largely attributed to its sesquiterpene lactones and flavonoid constituents. To investigate the neuroprotective and anti-stress potential of Inulae Flos, the present study employed a corticosterone-induced PC12 cell model, which mimics stress-induced neuronal dysfunction. In this study, hot-water and ethanolic extracts of Inulae Flos were evaluated for their protective effects on ROS generation, inflammatory cytokines, apoptosis and neurotrophic signaling including BDNF, NGF, and CREB activation in corticosterone-induced PC12 cells. The extracts significantly restored cell viability and reduced ROS production and apoptotic cell death. Western blot analysis revealed that Inulae Flos extracts upregulated the phosphorylation of CREB and enhanced the expression of BDNF and NGF, while suppressing the phosphorylation of ERK and p38 MAPK involved in inflammatory signaling. Markedly, Inulae Flos extract increased BDNF expression to the level comparable to the positive controls, L-theanine and fluoxetine. These findings demonstrate that Inulae Flos exerts a potent neuroprotective effect against glucocorticoid-induced neuronal stress by modulating oxidative, inflammatory, and neurotrophic pathways. The results suggest that Inulae Flos extract has promising potential as a functional ingredient for stress alleviation and brain health improvement.