Tiaobu Xinshen Recipe () Improved Mild Cognitive Impairment of Alzheimer's Disease Patients with Xin (Heart) and Shen (Kidney) Deficiency.

OBJECTIVE: To observe the intervention effects of Tiaobu Xinshen Recipe (, TXR) on patients with mild cognitive impairment caused by Alzheimer's disease (MCI-AD). METHODS: Totally 88 MCI-AD patients with syndrome of Xin (Heart) and Shen (Kidney) deficiency were assigned to the experimental group (47 cases, treated with TXR) and the control group (41 cases, treated with donepezil hydrochloride) using a random number table. Final recruited qualified patients were 44 cases in the experimental group and 39 cases in the control group. The therapeutic course was 12 weeks. Neuropsychological scales [mini mental state examination (MMSE) and Montreal cognitive assessment (MoCA)], and Chinese medicine (CM) dementia syndromes scales were performed in all patients, and results were compared between groups or intra-group before and after treatment. RESULTS: MMSE and MoCA scores of the two groups were increased after treatment compared with those before treatment (P<0.05). But there was no statistical difference in MMSE or MOCA scores after treatment between the two groups (P>0.05). CM dementia syndrome score was significantly decreased after treatment in the experimental group compared with the control group (P<0.01). Visual spatial and executive function scores and delayed recall scores of the two groups were increased compared with those before treatment (P<0.01). CONCLUSION: TXR could effectively improve cognitive impairment of MCI-AD patients with syndrome of Xin and Shen deficiency.

Characterization of astrocytes and microglial cells in the hippocampal CA1 region after transient focal cerebral ischemia in rats treated with Ilexonin A.

Ilexonin A is a compound isolated from the root of Ilex pubescens, a traditional Chinese medicine. Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the peri-infarct area after ischemia. However, the effects of ilexonin A on astrocytes and microglia in the infarct-free region of the hippocampal CA1 region remain unclear. Focal cerebral ischemia models were established by 2-hour occlusion of the middle cerebral artery in rats. Ilexonin A (20, 40 or 80 mg/kg) was administered immediately after ischemia/reperfusion. The astrocyte marker glial fibrillary acidic protein, microglia marker Iba-1, neural stem cell marker nestin and inflammation markers were detected by immunohistochemistry and western blot assay. Expression levels of tumor necrosis factor-α and interleukin 1ß were determined by enzyme linked immunosorbent assay in the hippocampal CA1 tissue. Astrocytes were activated immediately in progressively increasing numbers from 1, 3, to 7 days post-ischemia/reperfusion. The number of activated astrocytes further increased in the hippocampal CA1 region after treatment with ilexonin A. Microglial cells remained quiescent after ischemia/reperfusion, but became activated after treatment with ilexonin A. Ilexonin A enhanced nestin expression and reduced the expression of tumor necrosis factor-α and interleukin 1ß in the hippocampus post-ischemia/reperfusion. The results of the present study suggest that ilexonin A has a neuroprotective effect in the hippocampus after ischemia/reperfusion, probably through regulating astrocytes and microglia activation, promoting neuronal stem cell proliferation and reducing the levels of pro-inflammatory factors. This study was approved by the Animal Ethics Committee of the Fujian Medical University Union Hospital, China.

Ilexonin A Promotes Neuronal Proliferation and Regeneration via Activation of the Canonical Wnt Signaling Pathway after Cerebral Ischemia Reperfusion in Rats.

Aims. Ilexonin A (IA), a component of the Chinese medicine Ilex pubescens, has been shown to be neuroprotective during ischemic injury. However, the specific mechanism underlying this neuroprotective effect remains unclear. Methods. In this study, we employed a combination of immunofluorescence staining, western blotting, RT-PCR, and behavioral tests, to investigate the molecular mechanisms involved in IA regulation of neuronal proliferation and regeneration after cerebral ischemia and reperfusion in rodents. Results. Increases in ß-catenin protein and LEF1 mRNA and decreases in GSK3ß protein and Axin mRNA observed in IA-treated compared to control rodents implicated the canonical Wnt pathway as a key signaling mechanism activated by IA treatment. Furthermore, rodents in the IA treatment group showed less neurologic impairment and a corresponding increase in the number of Brdu/nestin and Brdu/NeuN double positive neurons in the parenchymal ischemia tissue following middle cerebral artery occlusion compared to matched controls. Conclusion. Altogether, our data indicate that IA can significantly diminish neurological deficits associated with cerebral ischemia reperfusion in rats as a result of increased neuronal survival via modulation of the canonical Wnt pathway.

Neuroprotective effects of Ilexonin A following transient focal cerebral ischemia in rats.

Ilexonin A is a compound isolated from the root of a plant commonly used in traditional Chinese medicine. The aim of the present study was to investigate the possible protective mechanism of Ilexonin A in rats subjected to occlusion of the middle cerebral artery (MCAO). Transient focal cerebral ischemia was induced by 2 h of MCAO, followed by reperfusion. Ilexonin A at doses of 20, 40 and 80 mg/kg were administered via intraperitoneal injection immediately following ischemia/reperfusion. The expression levels of glial fibrillary acidic protein (GFAP), ionized calcium­binding adapter molecule­1 (Iba­1), vascular endothelial growth factor (VEGF), fetal liver kinase­1 (Flk­1) and Nestin were examined using immunostaining and Western blot analysis of the peri­infarct region following ischemia/reperfusion. Ilexonin A significantly decreased the infarct volume and improved neurological deficits in a dose­dependent manner. The expression levels of VEGF, Flk­1 and Nestin were significantly increased in the rats treated with Ilexonin A, compared with the rats administered with saline. Following treatment with Ilexonin A, a higher number of GFAP­positive astrocytes were found in the Ilexonin A­treated rats at 1, 3 and 7 days, compared with the rats exposed to ischemia only, however, there were fewer astrocytes at 14 days, compared with the ischemia group. Ilexonin A significantly decreased the protein expression of Iba­1. The results of the present study suggested that the protective effects of Ilexonin A were associated with revascularization, neuronal regeneration, and the regulation of astrocyte and microglia cell activation.

[Changes of left ventricular remodeling in hypertension patients with carotid atherosclerosis of phlegm-dampness syndrome].

OBJECTIVE: To study changes of left ventricular remodeling (LVR) in hypertension patients with carotid atherosclerosis (CAS) of phlegm-dampness syndrome (PDS). METHODS: Doppler ultrasonography data of CAS were observed in 223 hypertension patients with CAS (as the hypertension group, including 119 patients of the PDS group and 104 of the non-PDS group), 81 CAS patients with non-hypertension, and 19 non-hypertension non-CAS patients (as the control group). The difference in the degree of LVR was compared among the above groups. RESULTS: The left ventricular posterior wall thickness (LVPWT), inter ventricular septum thickness (IVS), E/A were higher in the hypertension group than in the non-hypertension group (P < 0.05). The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), stroke volume (SV) were higher in the soft plaque hypertension group and the soft plaque non-hypertension group than in the hard plaque group, the thickening intimal group, and the normal intimal group (P < 0.01 , P < 0.05). The LVEDD, LVESD, and SV were higher, and the ejection fraction (EF) was lower in the PDS hypertension group than in the non-PDS hypertension group (all P < 0.05). Of them, LVEDD, LVESD, and SV were higher in the soft plaque group than in the hard plaque group (P < 0.01), the thickening intimal group (P < 0.01) and the normal intimal group (P < 0.05). There was no statistical difference in PDS hypertension between the soft plaque group and the hard plaque group (P > 0.05). CONCLUSION: The hypertension patients with CAS of PDS might be correlated to LVR, and LVR was more obviously in the soft plaque patients.

[Correlation study between carotid atherosclerosis and hypertension].

OBJECTIVE: To study the correlation between carotid atherosclerosis (CAS) and hypertension. METHODS: Color Doppler ultrasonography data of CAS were observed in 150 hypertension patients [as the hypertension group, including 70 patients in the phlegm-stasis syndrome (PSS) group and 80 in the non-PSS group] and 30 non-hypertension patients (as the control group). The difference of the CAS occurrence was compared among the three groups. RESULTS: The incidence of CAS was higher in the PSS group and the non-PSS group than in the control group, showing statistical difference (P<0.01). Of them, it was higher in the PSS group than in the non-PSS group (P<0.05). Hard plaque dominated in the CAS plaque constitution in both the PSS group and the non-PSS group. Of them the soft plaque ratio was higher in the PSS group than in the non-PSS group, showing statistical difference (41.9% vs 11.4%, P<0.05). The CAS plaque distribution positions among the three groups (P>0.05). The inner diameters of the left and right common carotid artery, and the resistant indices of the left and right common carotid artery, the left internal carotid artery, and the left vertebral artery in the PSS group and the non-PSS group were higher than in the control group (P<0.05). CONCLUSIONS: Hypertension patients are often accompanied with CAS of various degrees. Especially the soft plaque ratio of the CAS plaque was higher in those of PSS, indicating the possibility of target organs damage such as cerebral infarction was higher.