Catenin signaling pathway. Taking benefit of CUMS as a valuable model to study desperate behavior [53], we also found that crocin reversed the desperate behavior, activated Wnt/b-catenin signaling and promoted the proliferation and differentiation of hippocampal neurons. Interestingly, crocin increased the survival price of newborn neurons in CUMS mice (Fig. 8G), but not in standard mice (Fig. 2F), which indicated that crocin exhibited no effect around the normal apoptosis of neurons in the state of low tissue harm but could minimize the pathological harm to hippocampal neurons brought on by external stimuli, meanwhile, with reduced unwanted effects. Having said that, there’s nonetheless a limited quantity of well-controlled, numerous center clinical trials to provide the evidence of antidepressant action of crocin. Additionally, it is better to clarify the effect of crocin on Wnt/ b-catenin signaling activation in a much more simplified experimental program or in a particular kind of cells. Therefore, further investigation works are desperately needed. In summary, the existing study displayed that crocin exerted antidepressant effects with reduced unwanted side effects than fluoxetine. We showed that the antidepressant response of crocin was accompanied by hippocampal neurogenesis in mice and activation of the Wnt/b-catenin cascade. These final results elucidated a neuronal basis for the antidepressant impact of crocin, demonstrating the essential role of neurogenesis. Our studies offered the foundation for further establishment of crocin application for enhancing the treatment outcome of depression.Acknowledgement This operate was supported by National Organic Science Foundation of China (81873096, 82174002, 81874374), Key research and development projects of east-west cooperation (2021BEG02040), Open Projects with the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine Supported by the Topic of Academic priority discipline of Jiangsu Greater Education Institutions (NO. ZYX03KF73), and Blue Project of Middle-aged in Jiangsu province (2020).Appendix A. Supplementary material Supplementary data to this article is often discovered online at doi.org/10.1016/j.jare.2022.02.015.
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