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.

Efficacy of Baishao Luoshi decoction on synaptic plasticity in rats with post stroke spasticity.

OBJECTIVE: To evaluate the efficacy of Baishao Luoshi decoction (, BD) on synaptic plasticity in rats with post stroke spasticity (PSS), and to study the mechanism behind the action. METHODS: The PSS model of rat was established by middle cerebral artery occlusion (MCAO). The neurological deficit symptoms were evaluated by modified neurological deficit score (mNSS). Muscle tension were evaluated by Modified Ashworth score (MAS). Transmission electron microscopy (TEM) was used to observe the synaptic ultrastructure. The expression of synaptic plasticity-related protein brain derived neurotrophic factor (BDNF), growth associated protein-43 (GAP43), synaptophysin (p38) and microtubule-associated protein 2 (MAP2) in the brain tissue around the infarct were detected by Western blotting. RESULTS: We found that mNSS were significantly improved and limb spasticity was ameliorated treated by BD. The thickness of postsynaptic density and the synaptic curvature increased significantly. The expression of synaptic plasticity-related protein BDNF, GAP43, p38, MAP2 in the brain tissue around the infarct were raised remarkably after treated by BD. CONCLUSIONS: Alleviating PSS by BD may be related to rescuing the synaptic plasticity, which provides a probable new therapeutic method for PSS.