Synthesis and Evaluation of a Series of New Bulleyaconitine A Derivatives as Analgesics.

As a nonaddictive analgesic widely used in clinics, the LD50 of bulleyaconitine A is just only 0.92 mg/kg, which exhibits obvious toxicity. Therefore, 31 new non-natural C19-diterpenoid alkaloids (2a-w, 2'a-e, 3, 4a, and 4b) were designed and synthesized from bulleyaconitine A to develop nonaddictive analgesics with low toxicity. The chemical structures were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) spectra. The analgesic activities were evaluated by a hot plate test in mice. At the dosage of 10 mg/kg, six compounds (2d, 2j, 2k, 2m, 2t, 2w) exhibited good analgesic activities (increased pain threshold >100%) with a long duration. Among them, 2w showed the best analgesic activity and the longest duration. Its pain threshold reached 166.35% in 15 min, peaked at 30 min (182.35%), and remained 82.59% even at 60 min.

Role of Ginkgo biloba extract as an adjunctive treatment of elderly patients with depression and on the expression of serum S100B.

OBJECTIVE: To explore the effect of ginkgo biloba extract (EGb) as an adjunctive treatment of elderly patients with depression and the effect on the expression of serum S100B. METHODS: 136 elderly patients with depression were divided into EGb +  citalopram (Cit) group and Cit group equally. Efficacy was evaluated by Hamilton Depression Rating Scale (HAMD). Wisconsin Card Classification Test (WCST) was used to evaluate cognitive function. Serum S100B expression was measured with ELISA. The relationship of S100B with HAMD, Hamilton Anxiety Scale (HAMA) score, and WCST results was evaluated subsequently. RESULTS: The time of onset of efficacy was significantly shorter in EGb + Cit group. There were significant differences in HAMD and HAMA scores after treatment than before treatment between groups (all P < .05). After treatment, total number of WCST test, the number of continuous errors and non-persistent errors in both groups were less than those before treatment. The correct number and classifications number were increased than before treatment. In EGb + Cit group, correct numbers and classifications were increased, and the number of persistent errors was decreased. After treatment, S100B level was decreased, and S100B levels change in EGb + Cit group was greater than in Cit group. Serum S100B level was positively correlated with HAMD and HAMA scores before treatment and positively correlated with persistent errors number in WCST. CONCLUSION: EGb, as an adjunctive treatment, can effectively improve depressive symptoms and reduce expression of serum S100B, which is a marker of brain injury, suggesting that EGb restores neurologic function during the treatment of depression in elderly patients and S100B participates in the therapeutic mechanism. EGb combined with depressive drugs plays synergistic role, and the time of onset of efficacy is faster than single antidepressants.

MicroRNA-126 is down-regulated in human esophageal squamous cell carcinoma and inhibits the proliferation and migration in EC109 cell via PI3K/AKT signaling pathway.

MicroRNA-126 (miR-126) was found down-regulated in different types of cancer including esophageal squamous cell carcinoma (ESCC). However, the onco-genetic role of miR-126 in ESCC still remains unknown. In the present study, we found the relative expression of miR-126 in ESCC was significant decreased in ESCC tissues compared to adjacent normal tissues. Overexpression of miR-126 in EC109 cells resulted in significant decrease in cell proliferation, colon formation and migration. PI3K regulatory subunit p85 beta (PIK3R2), a member of PI3K/AKT signaling pathway was found upregulated in ESCC tissues and there is a negative relation between expression of PIK3R2 and miR-126. Restoration of miR-126 in EC109 cells induced a reduction in PIK3R2 protein levels, accompanied with a substantial reduction in phosphorylated AKT levels in EC109 cells, suggesting impairment in PI3K/AKT signaling pathway. The luciferase reporter assay confirmed that PIK3R2 was a direct target of miR-126. Furthermore, we also indicated overexpression of miR-126 suppresses G2/M transition in EC109 cells. Taken together, our study suggests that miR-126 functions as a potential tumor suppressor in ESCC progression via regulating PI3K/AKT signaling pathway partly by targeting PIK3R2, and targeting of miR-126 may provide a novel strategy for the diagnosis and treatment of ESCC.