6-BA is a common plant growth regulator, but its safety has not been conclusive. The heart is one of the most important organs of living organisms, and the cardiogenesis process of zebrafish is similar to that of humans. Therefore, based on wild-type and transgenic zebrafish, we explored the development of zebrafish heart under 6-BA exposure and its mechanism. We found that 6-BA affected larval cardiogenesis, inducing defective expression of key genes for cardiac development (myl7,vmhc, andmyh6) and AVC differentiation (bmp4,tbx2b, andnotch1b), ultimately leading to weakened cardiac function (heart rate, diastolic speed, systolic speed). Acridine orange staining showed that the degree of apoptosis in zebrafish hearts was significantly increased under 6-BA, and the expression of cell-cycle-related genes was also changed. In addition, HPA axis assays revealed abnormally expressed mRNA levels of genes and significantly increased cortisol contents, which was also consistent with the observed anxiety behavior in zebrafish at 3 dpf. Transcriptional abnormalities of pro- and anti-inflammatory factors in immune signaling pathways were also detected in qPCR experiments. Collectively, we found that 6-BA induced cardiotoxicity in zebrafish, which may be related to altered HPA axis activity and the onset of inflammatory responses under 6-BA treatment.Keywords:zebrafish;6-benzylaminopurine;cardiotoxicity;HPA axis activity;inflammation
Perimenopausal depression is a psychiatric disorder that occurs around the time of menopause and seriously affects women's health. The pathogenesis of perimenopausal depression is unclear which affects its prevention and treatment. Quercetin is a flavonoid compound with antidepressant and estrogen-like effects. The aim of this research was to investigate the role of quercetin on adrenal gland metabolic disorders in perimenopausal depressed rats based on untargeted metabolomics. Female Wistar rats with no difference in sucrose preference were randomly separated into four groups (n = 12): sham-operated group; perimenopausal depression model group; model + 50 mg/kg.bw quercetin group; model + 0.27 mg/kg.bw 17β-estradiol group. After successful modeling, adrenal gland and hypothalamic samples were collected for metabolomics experiments and detection of related indicators. A total of 22 differential metabolites were identified in the model group, and pathway analysis revealed adrenal gland metabolism abnormalities including steroid hormone biosynthesis, arachidonic acid metabolism, and linoleic acid metabolism. Notably, Spearman’s rank correlation analysis between differential metabolites and rat behavioral results showed strong positive or negative correlations ( P < 0.01). Meanwhile, the hypothalamus of the model group showed TrkB-BDNF signaling pathway abnormality, and the HPA axis was found to play an important role in perimenopausal depression. Treatment with quercetin or 17β-estradiol restored these abnormal changes. It suggested that quercetin can regulate adrenal metabolic disorders through multiple pathways, thereby ameliorating perimenopausal depression.Further more, quercetin can modulate HPA axis through the TrkB-BDNF signaling pathway. This research provides new ideas for the application of quercetin in the precaution and treatment of perimenopausal depression.
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