<i>Aster spathulifolius</i> 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. <i>Aster spathulifolius</i> 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 <i>Aster spathulifolius</i> 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.