Glycyrrhizic acid as an adjunctive treatment for depression through anti-inflammation: A randomized placebo-controlled clinical trial.

BACKGROUND: Recently, abundant evidence indicated proinflammatory cytokines might play a crucial role in pathophysiology and treatment of depression. According to our preclinical research, we propose glycyrrhizic acid (GZA) for an adjunctive treatment owing to its safety, economical and anti-inflammatory profile. METHODS: Eligible participants were recruited and randomly allocated into independent treatment groups of SSRI+GZA (n = 30) and SSRI+PBO (placebo, n = 26). Depressive symptoms and specific serum biomarkers were detected during the 4-week treatment course. Afterward, the relationships between biomarkers and clinical effects were explored. RESULTS: Depressive symptoms relieved more in SSRI+GZA than SSRI+PBO, both at week 2 (P = 0.003) and week 4 (P = 0.016). Meanwhile, at week 4, both response rate (P = 0.035) and remission rate (P = 0.031) acutely became higher in SSRI+GZA compared with SSRI+PBO. Mediation analysis further demonstrated that TNF-α reduction mediated the association between GZA treatment and clinical improvement, the indirect effect lay between 0.124 and 3.514 (95% CI). The exploratory analysis also suggested that the symptomatic improvement existed in patients with high-inflammation (baseline CRP > 3 mg/L) rather than those with low-inflammation (baseline CRP ≤ 3 mg/L). LIMITATIONS: The sample size in this study was not large enough and the follow-up duration was relatively short. CONCLUSIONS: This study offers a novel strategy for the diagnosis, categorization, individualization and prognosis regarding upgrading traditional antidepressant therapy, which is from biomarkers to diagnostic indicator and therapeutic target. Patients are necessary to be classified according to the inflammatory state, those with high levels of baseline inflammation should receive combined treatment with anti-inflammatory agents like GZA.

High-mobility group box-1 was released actively and involved in LPS induced depressive-like behavior.

Depression disorder is a common mental illness, of which the pathogenesis is not well understood. Studies suggest that immunity imbalance and up-regulation of pro-inflammatory cytokines may be associated with the pathogenesis of depression. High-mobility group box 1 protein (HMGB1) has gained much attention as an important player in innate immune responses and an modulating factor in several inflammatory diseases. Here we sought to explore the role of HMGB1 in the development of depression. Depression model was established with low dose of lipopolysaccharide (LPS) administration. Depressive behavior was reflected with increased immobility time in tail suspension test. Accompanying with depressive-like behavior, translocation of HMGB1 from nuclei to cytoplasm was observed by immunofluorescence assays. Meanwhile, no significant necrosis was observed evaluated by hematoxylin-eosin staining. These data indicated that HMGB1 was released actively in the central nervous system. In addition, treating the mice with human recombinant HMGB1 (rHMGB1) could induce the development of depressive-like behavior. Blockage of HMGB1 with GZA abrogated the depressive-like behavior induced by LPS or rHMGB1. These results implicated that HMGB1 was involved in LPS-induced depressive-like behavior.

[Flavonoids of puerarin versus tanshinone II A for ischemic stroke: a randomized controlled trial].

BACKGROUND: Flavonoids are widely used today in the treatment of ischemic stroke. The therapeutic effects and functions of flavonoids are, therefore, generating more and more interest. OBJECTIVE: To investigate the therapeutic effects and functions of flavonoids of puerarin in treating patients with ischemic stroke. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 67 inpatients suffering from ischemic stroke from the Department of Neurology, Changhai Hospital in China were divided into two groups randomly, the treatment group, which was treated with flavonoids of puerarin, and the control group, administered with tanshinone II A sulfate instead. MAIN OUTCOME MEASURES: Defects in neurological function were evaluated according to the National Institutes of Health Stroke Scale (NIHSS) on the first day of onset. Lactate dehydrogenase (LDH), serum interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) levels were determined by radioimmunoassay on the second trial day. After a 14-day treatment, LDH, serum IL-6 and BDNF levels and NIHSS score were also detected, and CT perfusion imaging was used to measure and analyze the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time (MTT). RESULTS: On the first day, NIHSS scores of the two groups were similar. On the second day there was no significant difference in LDH and IL-6 levels between the treatment group and the control group. After a 14-day treatment, LDH and IL-6 levels and the NIHSS score in the treatment group were lower than those in the control group (P<0.05). There was no significant difference in BDNF levels in the two groups. After 14 d, the CT perfusion imaging demonstrated that the treatment group showed more effective blood perfusion than the control group. CONCLUSION: Flavonoids of puerarin can restrain the increase of IL-6 after acute ischemic stroke, and depress the LDH raised by reperfusion after cerebral ischemia. It can also enhance blood perfusion of the ischemic region.

[Effects of prenatal methylmercury exposure on learning and memory ability of mice and ultrastructure of hippocampus neurons in mice].

OBJECTIVE: To study the effects of prenatal methylmercury exposure on learning and memory ability of mice and ultrastructure of hippocampus neurons in mice. METHODS: Methylmercury in doses of 0 and 4mg/(kg x d) were fed to pregnant mice at 7th-9th day after conception. Learning and memory ability of the mice offspring was detected. The ultrastructure of hippocampus neurons was observed by electron microscope after the completion of the experiment. RESULTS: The learning and memory ability of the mice offspring of 4 mg/(kg x d) dose group was lower than those of 0 mg/(kg x d) dose group (P < 0.05). Changes in the ultrastructure of hippocampus neurons were obvious in 4 mg/(kg x d) dose group as compared with the 0 mg/(kg x d) dose group. CONCLUSION: Methylmercury could affect the growth and development of central nerve system. The learning and memory ability of mice offspring was greatly damaged and the ultrastructure of hippocampus neurons was changed by methylmercury.