Progress in Neuro-psychopharmacology & Biological Psychiatry · Jun 13, 2026

Cajanine protects against menopausal mood disorders and concomitant metabolic dysfunctions in ovariectomized mice via ERβ-mediated pathways

By Yan Q, Wu F, Xu P et al.

Menopausal mood disorders (MMD) are common neuropsychiatric symptoms in postmenopausal women, often accompanied by metabolic dysfunctions. This study aimed to investigate the therapeutic effect of cajanine on MMD and its underlying mechanism, with its therapeutic potential for metabolic abnormalities and the relevant mechanism as an exploratory objective. Network pharmacology was used to predict the potential targets of cajanine in the treatment of MMD. Estrogen receptor β (ERβ) was identified as its most promising binding target, and Estrogen Response Element (ERE)-luciferase reporter assay confirmed the functional activation of ERβ by cajanine. Animal experiments showed that cajanine significantly alleviated depression and anxiety behaviors in ovariectomized (OVX) mice. Biochemical analysis revealed that cajanine significantly upregulated ERβ expression and reversed the abnormal levels of nuclear factor kappa-B (NF-κB), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase-3 in the hippocampus and amygdala of OVX mice. The use of ERβ antagonist and agonist further confirmed that cajanine exerts its beneficial effects on mood disorders by suppressing neuroinflammation and regulating apoptotic pathways in an ERβ-dependent manner. Exploratory analysis revealed that cajanine also alleviated weight gain and metabolism abnormalities in OVX mice. The ameliorative effects of cajanine on weight change and metabolism abnormalities were associated with the regulation of peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor γ (PPARγ) in liver and adipose tissues, which was also mediated by ERβ. In conclusion, cajanine exerts estrogen-like activity via ERβ to exert a multi-target therapeutic effect, thereby treating MMD and its coexisting metabolic abnormalities.

doi.org/10.1016/j.pnpbp.2026.111777 PubMed 42288306 Interventions