Aster spathulifolius Maxim. Alleviates Primary Dysmenorrhea in a Mouse Model by Modulating Myometrial Contractions via NF-κB/COX-2 Pathway Inhibition.

Primary dysmenorrhea (PD) is characterized by excessive uterine contraction and ischemic vasoconstriction, primarily driven by elevated levels of prostaglandins (PGs; PGF2α) and inflammatory mediators. Nonsteroidal antiinflammatory drugs (NSAIDs) remain the standard treatment for PD; however, their associated adverse effects necessitate the use of alternative therapeutic strategies. Aster spathulifolius Maxim. is a perennial herb native to the coastal regions of Korea, that exhibits antiviral, anticancer, and antidiabetic effects. In this study, we investigated the potential of Aster spathulifolius Maxim. extract (PDR97) to alleviate PD in both animal models and human uterine smooth muscle cells (HUtSMCs). Our findings demonstrated that PDR97 significantly reduced pain-related responses and restored uterine morphology in PD-induced mice. Mechanistically, PDR97 suppressed the expression of uterine contraction-related proteins, decreased NF-κB phosphorylation, and downregulated the expression of proinflammatory cytokines. Furthermore, PDR97 effectively inhibited PGF2α- and interleukin-1β (IL-1β)-induced reactive oxygen species (ROS) production in both the PD mouse model and HUtSMCs, exhibiting potent antioxidant properties. Notably, PDR97 modulated NF-κB signaling-a key regulatory pathway associated with uterine contraction and pain relief-and its antioxidant effects contributed to the suppression of inflammatory and oxidative stress-mediated signaling. Collectively, these findings highlight the potential of PDR97 as a promising natural therapeutic agent for PD, with potential applications in other gynecological disorders associated with inflammation and oxidative stress.