Remedial Effect of α-tocopherol and Tocotrienol-rich Palm Oil Extract on Primary Dysmenorrhea-associated Mood Dysfunction in Mice

Introduction: Primary dysmenorrhea is manifested as uterine cramps before and/or during menstruation without pelvic disease, which causes painful menstruation. Many patients with primary dysmenorrhea expressed the presence of emotional depression, anxi-ety, and stress. Vitamin E has been demonstrated to reduce menstrual pain, but its impact on primary dysmenorrhea-related mood responses remains unexplored. Methods: The present report examined the ameliorative effects of α-tocopherol (α-T) and tocotrienol-rich palm oil extract (TRPO) on a mouse model of primary dysmenorrhea, in-duced by oxytocin injection in estrogen-primed female mice. The depressive- and anxiety-like responses were tested via the open field. Social interaction and tail suspension test. The serum corticosterone and hippocampal pro-inflammatory cytokine levels were measured via an ELISA test. Results: Our study revealed that mice induced with primary dysmenorrhea, via estradiol and oxytocin injections, exhibited depressive- and anxiety-like behaviors. Treatment with α-T (50 and 100 mg/kg) and TRPO (100 and 200 mg/kg) via the oral route significantly modu-lated these behavioral changes. Interestingly, treatment with TRPO, but not α-T, signifi-cantly modulated the increased serum corticosterone level. An ELISA study on the hippo-campal tissue showed that α-T and TRPO significantly suppressed elevated IL-1β and IL-6, but only TRPO inhibited the elevated TNF-α. Discussion: The results suggested that TRPO relieved primary dysmenorrhea-related mood disorders, at least in part, by modulating the stress-related and pro-neuroinflammatory path-ways, with a slightly different mechanism than α-T. Conclusion: This study's findings may establish a new basis for utilizing vitamin E or its isomers in treating depressive and anxiety-like responses associated with primary dysmen-orrhea, thereby enhancing women's health.