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Blood-brain barrier (BBB) is a barrier which maintains the material exchange balance of brain microenvironment and could be destroyed by chronic stress (CS). Glucocorticoids (GCs) can mimic the chronic stress induced damage to BBB. GCs induced BBB trauma models in vitro and in vivo to explore the effects of the traditional medicine Xiao-Yao-San (XYS). In this research, we found CS could injure the BBB to change the biochemical index, which could be reversed by XYS in vitro. The abilities of cell proliferation, invasion, and the expression of tight junction related genes (Occludin, Claudin, JAM-1 and ZO-1) were suppressed by CS and the trauma could be reversed by XYS partly. It was showed that GRs interacted with Occludin directly and inhibited Occluding expression. In rats BBB trauma model, the GC content was deceased and BBB permeability was repaired by XYS. The expression of Occludin, Claudin, JAM-1 and ZO-1 were increased in the treatment of XYS. In our research, it shown that XYS affect the content of the GC and GR which interacted with Occludin directly for the first time. In addition, we also found that XYS could reduce BBB injury induced by CS via GR in BBB model in vitro. Therefore, it proves that XYS is a potential BBB repair medicine and may help to elucidate mechanism of brain pathology., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent researches have shown that autophagy is associated with the pathogenesis of neurodegenerative disorders, but there is no paper to investigate the effects of autophagy modulation on Parkinson's disease depression (PDD). In addition, glycyrrhizic acid (GA), the major bioactive ingredient of Radix glycyrrhizae, can induce autophagy and ease rotenone-induced Parkinson's disease (PD). However, there is also no paper to study the action and molecular mechanisms of GA on PDD. In this research, we built the injury model of SH-SY5Y cells through 6-hydroxydopamine (6-OHDA) and corticosterone (CORT). Then, our results showed that GA markedly increased the viability and decreased the apoptosis in SH-SY5Y cells after pre-treating with 6-OHDA and CORT. Moreover, GA notably decreased the expressions of α-Syn and p-S1292-LRRK2 proteins, and significantly increased the levels of CREB and BDNF proteins. Previous papers have suggested that CORT contributed to dopaminergic neurodegeneration via the glucocorticoid (GC)/glucocorticoid receptor (GR) interaction, and our results showed that GA reduced GC level and hypothalamic-pituitary-adrenal (HPA) activity in SH-SY5Y cells by regulating GR signaling pathway. Furthermore, mechanism investigations also showed that GA had the ability to up-regulate the conversion of LC3B II/I and the expression of Beclin-1, and induce autophagy in SH-SY5Y cells, which were reversed by the autophagy inhibitor 3-methyladenine (3-MA). Collectively, these findings proved that GA exerted efficient activity against neurotoxicity in SH-SY5Y cells induced by 6-OHDA and CORT via activation of autophagy, which should be developed as an efficient candidate for treating PDD in the future.

Background: Depression is characterized by a pathological injury to the hippocampal neurons. Senkyunolide A (SenA) is one of the major active components of Dan-zhi-xiao-yao-san, which is widely used in the treatment of depression-related disorders., Materials and Methods: In the present study, it was hypothesized that the antidepressant effect of Dan-zhi-xiao-yao-san depended on the function of SenA and the authors attempted to reveal the molecular mechanism associated with the treatment. An in vitro depression model was induced using corticosterone (Cort), and the effect of SenA on the cell viability, apoptosis, and protein phosphatase 2A/α-synuclein (PP2A/α-syn) signaling was detected. To validate the mechanism driving the therapeutic effect of SenA, activity of PP2A and α-syn was modulated and the effect on neural cells was evaluated., Results: The results showed that SenA protects Cort-induced cell apoptosis in PC12 cells. In addition, SenA increased Cort-induced reduction of PP2A activity, while it decreased the expression of p-PP2A, α-syn, and p-α-syn (Ser129). Further, modulation of PP2A activity with specific inhibitor okadaic acid (OA) increased Cort-induced cell apoptosis, while PP2A activator D-erythro-sphingosine (SPH) exhibited an opposite effect. The neuroprotective effects of SenA on neural cells also depended on inhibition of α-syn function, the regulation of which would influence the activity of PP2A in a negative loop., Conclusion: Collectively, the results suggested that the neuroprotective effects of SenA were exerted by modulating activities of PP2A activities and α-syn. The findings partially explained the mechanism associated with the neuroprotective effect of SenA., Competing Interests: Disclosure The authors report no conflicts of interest in this work.