Major depression has various types of symptoms and disease courses with inconsistent response to monoamine-related antidepressants. Thus, monoamine theory may not be the only pathophysiologic pathway relevant to depression. Recently, it has been suggested that regulatory T cell (Treg) is associated with depression. Based on our previous study that showed decreased regulatory T cell (Treg) population following chronic high-dose captopril (CHC, 40 mg/kg/day * 21 days) administration, we examined whether CHC alone can induce depressive-like behaviors in mice even without stressful stimuli. In this study, we found that CHC induced depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST) without systemic illness, while it did not induce anhedonic behavior, anxiety-like behaviors, or sociality-related behavior. The depressive-like behaviors were rescued by either CHC washout or antidepressant. CHC caused reduction in foxp3 and gata3 mRNA expression in the lymph nodes with elevation in plasma IL-1β and IL-6. Interestingly, CHC increased serum angiotensin II level. In the hippocampus, CHC increased TNF-α and IL-6 mRNA expression with microglia activation while reduced glucocorticoid receptor expression. However, CHC did not affect to hippocampal kynurenine pathway, serotonin level, hypothalamic corticotropin-releasing hormone mRNA level, or serum corticosterone level. Consequently, we propose that CHC may induce a specific form of depressive-like behaviors via Treg reduction and microglial activation.

We have designed the cyclopropane analog of stilbene as subtype-selective ligands for estrogen receptor based on the bioisosterism that cyclopropane could act as alkene bioisoster. Three cyclopropane analogs were prepared efficiently starting from 4-benzyloxybenzaldehyde, and evaluated for their binding to estrogen receptors ERα and ERβ. These cyclopropane analogs were also found to be full agonists in estrogen receptor-mediated gene transcription assay. Compared to the stilbene analogs such as tamoxifen and raloxifene, the three cyclopropane analogs showed lower binding affinity for estrogen receptor, but higher subtype selectivity for ERα. The structure-activity relationship revealed from this study might provide clues for improving subtype selectivity for ERα.

Micelles, which are called solubilization formulation, have been widely used in skin lotion, mist or various formulations for the purpose of solubilizing the fragrance rather than the role of the active ingredient carrier because the particles are very small. In this study, we developed the swollen micelle having a transparent appearance to deliver β-sitosterol. When preparing the swollen micelle, solubility parameter was considered with active ingredient. This method allowed insoluble active ingredient to be safely entrapped inside the micelles. Stability of micelle was evaluated by dynamic light scattering (DLS). The transparency and shape of the micelles were confirmed by cryo-TEM. In addition, through the thermal analysis using DSC, β-sitosterol was found to be stably present in the swollen micelles. These results indicate that swollen micelles considered solubility parameter could be used as a new carrier for the insoluble active ingredients.