Proliferation and differentiation of neural stem cells is regulated by autologous or external, adjacent or remote cell signaling pathways. This paper reviewed the studies about the Notch, BMP, Wnt, Shh signaling pathways related to brain neurogenesis.

Objective To study the effects of morroniside on the expression of Wnt signaling-related transcription factors neurogenin 2 (Ngn2), Pax6 and Tbr2 in the ischemic ipsilateral cortex 7 days after cerebral ischemia-reperfusion in rats. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of Ngn2, Pax6 and Tbr2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ngn2 increased in the ischemia group compared with the sham group (P<0.05), and it further increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference between the ischemia group and sham group in the expression of Pax6, while it increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference among all the groups in the expression of Tbr2. Conclusion Morroniside could increase the expression of Ngn2 and Pax6 in the ischemic ipsilateral cortex 7 days after ischemia-reperfusion in rats, suggesting promoting the neurogenesis after ischemia.

Objective To study the effects of morroniside on the expression of matrix metalloproteinase (MMP) -2 and MMP-9 in the peri- infarct cortex 3 days after cerebral ischemia- reperfusion. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of MMP-2 and MMP-9 in peri-infarct cortex were detected with immunohistochemistry staining 3 days after operation. Results The expression of MMP-2 and MMP-9 increased in the ischemia group compared with the sham group (P<0.01), and it decreased in all the morroniside groups compared with the ischemia group (P<0.01). Conclusion Morroniside could decrease the expression of MMP-2 and MMP-9 in the peri-infarct cortex 3 days after ischemia, suggesting protecting the function of blood-brain barrier from ischemia.

Tissues and organs generate angiogenesis under the stimulation of angiogenic factors in physiological or pathological conditions.Multiple signal pathways including VEGF, Notch, Wnt/β-catenin, Ang1(2)/tie2 and PIK-Akt etc.have effects on various stages of angiogenesis.VEGF exerts irreplaceable effects on the whole process of angiogenesis through multiple signal pathways.Over the past few years, new progress has been made in the researches of mechanisms regulating angiogenesis through VEGF-related signal pathways both at home and abroad.These findings provide us new theoretical basis for clarification of the pathogenesis of many diseases and clinical drug development.In this article we will summarize the recent research progress in this field, hoping to provide new possibilities for the treatment of angiogenesis-related diseases.

Objective To explore the effects of morroniside on the expression of Angiopoietin-1 (Ang-1) and Tie-2 in a rat after focal cerebral ischemia-reperfusion. Methods 20 male Sprague-Dawley rats were randomly divided into sham group (n=4), ischemia group (n=4), and morroniside groups (low, medium and high dosage groups, n=4). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg after operation. The expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ang-1 and Tie-2 increased in the ischemia group compared with the sham group (P<0.01), and both of them further increased in the morroniside groups of high dosage compared with the ischemia group (P<0.01), and the expression of Tie-2 also increased in the morroniside groups of medium dosage (P<0.001). Conclusion Morroniside could increase the expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, suggesting promoting the angiogenesis after ischemia.

Atherosclerosis is the common basic pathophysiology progresses of acute cardiovascular and cerebrovascular diseases. Atherosclerotic plaque rupture and consequently thrombosis are the major cause of mobility and mortality in atherosclerosis, and treatment aimed at stabilizing vulnerable plaques is of great clinical importance. However, an ideal drug for stabilizing vulnerable plaques is still lacking. Although Statins are considered as the most potent drugs for stabilizing plaques, their side effects are serious. Traditional Chinese medicine have multi-targets and less side effect, it might be the potential candidate for atherosclerosis treatment. This article reviewed the latest progresses on the stabilizing vulnerable plaques treatments.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative movement disorder in human being, characterized by progressive degeneration and lost of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc),causing low level of DA in the nigrostriatal pathway, eventually leading to motor dysfunctions including tremor, rigidity, bradykinesia,and postural instability.The pathology of PD is complex and the etiology remains poorly understood. In recent years,inflammation has been suggested to be involved in the occurrence and development of PD, by activation of microglia and overexpression of the inflammatory factors. And anti-inflammatory drugs has been developed to delay or prevent the progressive course of PD, becoming a new hotspot in treatment of PD. In this review, the latest progresses on the inflammatory mechanisms and anti-inflammatory treatments of PD was introduced.

Objective To investigate the effects of morroniside on hydrogen peroxide (H2O2)-induced calcium overload and cytotoxicity in SH-SY5Y neuroblastoma cells. Methods SH-SY5Y cells were pre-incubated with morroniside 1, 10, or 100 μmol/L for 24 h prior to exposure to H2O2 300~500 μmol/L for 18 h. The cytosolic free calcium concentration and LDH release were determined. Results The H2O2-induced cytosolic free calcium concentration decreased in the cells pre-incubated with morroniside 10 or 100 μmol/L, while the LDH release level decreased in the cells pre-incubated with morroniside 1, 10 or 100 μmol/L, comparison with the cells exposed H2O2 along. Conclusion Morroniside effects neuroprotection against H2O2-induced calcium overload and cytotoxicity in SH-SY5Y cell.

Objective To explore the effects of morroniside on platelet aggregation induced by adenosine diphosphate (ADP) in focal cerebral ischemia/reperfusion in rats. Methods 48 Sprague-Dawley rats were randomly divided into sham group, model group, morroniside dose groups (30 mg/kg, 90 mg/kg, 270 mg/kg) and acetyl salicilic acid (ASA) group (10 mg/kg). The model of middle cerebral artery occlusion (MCAO) was established in all rats except the sham group. Born's turbidimetry was used to measure platelet aggregation rate in rats of MCAO model (in vivo). Results Compared with the model group, the platelet aggregation decreased significantly in the morroniside high dose group (P<0.001). Conclusion Morroniside has the effect of anti-platelet aggregation in focal cerebral ischemia/reperfusion in rats.

Objective To investigate the effects of morroniside on fibrinogen (Fib), prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) in focal cerebral ischemia/reperfusion in rats. Methods The animal model was induced with occlusion of middle cerebral artery (MCAO) with suture embolus, and morroniside was then administered intragastrically at the dose of 30, 90 and 270 mg/kg for 7 d. Acetyl salicylic acid was taken as positive control drug. The content of Fib, and PT, APTT and TT were measured withrelated kits. Results Compared with the sham-operated group, the concentration of Fib significantly increased (P<0.001) and PT, APTT and TT significantly shortened in the model group (P<0.001); however, compared with the model group, morroniside significantly decreased Fib content (P<0.01) and prolonged PT, APTT and TT (P<0.05). Conclusion Morroniside can antagonize the coagulation function in focal cerebral ischemia/reperfusion in rats.