Luteolin promotes neuronogenesis in hippocampus of chronic unpredictable mild stress rats and primary hippocampus of fetal rats.

OBJECTIVE: To investigate the effects of luteolin on chronic unpredictable mild stress (CUMS)-induced depressive rats and corticosterone (CORT)-induced depressive primary hippocampal neurons, and to elucidate the mechanism behind the action. METHODS: The antidepressant mechanism of luteolin was studied by using CUMS rat model and primary hippocampal neurons in fetal rats. In vivo, novelty suppressed feeding, open-field and sucrose preference tests as well as Morris water maze were evaluated. The content of brain derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in serum were detected by enzyme-linked immunosorbent assay. The mechanisms of luteolin were explored based on neurotrophin and hippocampal neurogenesis, and proliferation. Survival of the septo-temporal axis in hippocampus was assayed using the 5-bromo-2-deoxyuridine (BrdU), the expression of BDNF, neurotrophin-3 (NT-3), and nerve growth factor (NGF) in hippocampus dentate gyrus region were measured by Western-blotting. In vitro, BDNF, NT-3, tropomyosin receptor kinase B (TrkB), and phosphorylated cyclic adenosine monophosphate responsive element binding protein (p-CREB) were detected through the high content analysis (HCA) to investigate neurotrophin and apoptosis. RESULTS: Induction of CUMS in rats induced depressive symptoms, while luteolin significantly enhanced sucrose consumption, decreased feeding latency, increased locomotor activity, escape latency, distance of target quadrant and regulated the content of depressive-like biomarkers. Histology analysis revealed that luteolin increased the abundance of new born neurons that had been labeled with BrdU, BrdU + neuronal nuclear antigen, and BrdU + doublecortin in septo-temporal axis of S2 (mid-septal) and T3 (mid-temporal). Moreover, expression of BDNF, NT-3, and NGF increased significantly in the septo-temporal axis of S2 and T3. HCA showed increased expression of BDNF, NT-3, TrkB and p-CREB in primary hippocampal neurons. CONCLUSION: The results provided direct evidence that luteolin has an antidepressant effect and could effectively promote the regeneration of the septotemporal axis nerve and hippocampal neuronutrition, which suggested that the antidepressant effect of luteolin may be related to hippocampal neurogenesis.

Simultaneous Determination of 5 Constituents in Xiao'er Magan Granule by HPLC-QAMS / 中国药师

Objective:To develop a method of quantitative analysis of multi-components by single marker(QAMS)for the determi-nation of five constituents(ephedrine hydrochloride,amygdalin,liquiritin, baicalin and ammonium glycyrrhizinate)in Xiao'er Magan granule. Methods:Amygdalin was used as the internal reference substance, and the relative correlation factors(RCF) of ephedrine hydrochloride,liquiritin,baicalin and ammonium glycyrrhizinate to amygdalin were calculated and evaluated. The contents of the five constituents were determined by the external standard method(ESM) and QAMS,respectively. The content results determined by the two methods were compared and the feasibility of QAMS method was verified. Results:The RCF between amygdalin and the other con-tents was 1.237,1.318,1.327 and 0.884,respectively. There were no significant differences in the results between QAMS and ESM with the relative errors less than 0.3%. Conclusion:The QAMS method is accurate and feasible for the simultaneous determination of Xiao'er Magan granule.