Gut microbiota mediated inflammation, neuroendocrine and neurotrophic functions involved in the antidepressant-like effects of diosgenin in chronic restraint stress.

BACKGROUND: Diosgenin is a well-known steroid saponin possessing neuroprotective activities. However, it is unknown whether diosgenin could alleviate depression-like symptoms. METHODS: The antidepressant-like effect of diosgenin was investigated in mice induced by chronic restraint stress. The effects of diosgenin on behaviors, inflammation, neuroendocrine, neurotrophic function, and gut microbiota were evaluated. RESULTS: The results showed that diosgenin alleviated the depressive-like behaviors in mice. In addition, diosgenin was found to reduce serum concentrations of proinflammatory cytokines and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Besides, diosgenin could activate hippocampal brain-derived neurotrophic factor (BDNF)/TrkB/ERK/CREB signaling pathway and improve the expression of postsynaptic protein PSD95. Meanwhile, the neurogenesis which was inhibited by chronic restraint stress, was totally reversed by diosgenin. Moreover, diosgenin increased the abundance of phylum Firmicutes and the genus Lactobacillus in stressed mice. The results further showed that diosgenin caused a strong correlation between gut microbiota composition and inflammation, the HPA axis activity, or hippocampus neurotrophic function. LIMITATIONS: Only male mice were used for evaluation in the present study, which limits the understanding of effects of diosgenin on the both sexes. In addition, the results only indicate microbiota at the phylum or genus mediate the regulation of neuroinflammation, neuroendocrine, and neurotrophic function, but does not elucidate how microbiota modulate the systems via their primary or secondary metabolites. CONCLUSIONS: The present study shows that diosgenin exerts the antidepressant activity, which is associated with the enhancement of neurotrophic function and the inhibition of inflammatory and neuroendocrine activities via the regulation of gut microbiota.

Dexmedetomidine Improves Lung Function by Promoting Inflammation Resolution in Patients Undergoing Totally Thoracoscopic Cardiac Surgery.

OBJECTIVE: Totally thoracoscopic cardiac surgery under cardiopulmonary bypass combined with one-lung ventilation has been identified as the trend in cardiac surgery. The aim of this study was to examine the effects of the selective α 2 adrenergic receptor agonist dexmedetomidine on the pulmonary function of patients who underwent mitral valve surgery using the totally thoracoscopic technique. METHODS: Fifty-seven patients who underwent thoracoscopic mitral valve surgery between July 2019 and December 2019 were selected. The patients were randomly divided into the control (Con) group (n = 28) and the dexmedetomidine (DEX) group (n = 29) using the random number table method. Arterial blood gas analyses were performed, and the oxygenation (PaO2/FiO2) and respiratory indexes (P(A-a)O/PaO2) were calculated 5 min after tracheal intubation (T1), 2 h after operation (T2), 6 h after operation (T3), and 24 h after operation (T4). Moreover, the serum cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were detected using the enzyme-linked immunosorbent method at all time points. Chest radiography was performed 24 h after surgery. Peripheral blood samples were collected before and after the operation for a complete hemogram. Additionally, the procalcitonin concentration was measured and recorded when the patients were transported to the intensive care unit (ICU). The postoperative extubation time, length of ICU stay, and pulmonary infection rate were also recorded. RESULTS: Inflammatory reaction after surgery was evident. However, the inflammatory cytokines IL-6, TNF-α, and ICAM-1 in the DEX group were lower than those in the Con group after surgery (T2 to T4; P < 0.05). Neutrophil counts and procalcitonin concentration were higher in the Con group than in the DEX group (P < 0.05). In addition, in the DEX group, pulmonary exudation on chest radiography was lower, and pulmonary function, as shown by an increase in oxidation index and decrease in the respiratory index, improved after surgery (P < 0.05). Moreover, the duration of mechanical ventilation in the Con group was 3.4 h longer than that in the DEX group. CONCLUSION: Dexmedetomidine has a protective effect on pulmonary function in patients undergoing mitral valve surgery using a totally video-assisted thoracoscopic technique, which may be related to a reduction in the concentration of inflammatory cytokines in the early perioperative period.