PI3K/Akt pathway contributes to neuroprotective effect of Tongxinluo against focal cerebral ischemia and reperfusion injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), a compound prescription, is formulated according to the collateral disease doctrine of traditional Chinese medicine, and is widely used for the treatment of cardio-cerebrovascular diseases in China. AIM OF THE STUDY: We aimed to investigate the neuroprotective effect of TXL on focal cerebral ischemia and reperfusion injury in rats by attenuating its brain damage and neuronal apoptosis, and to assess the potential role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in this protection. MATERIALS AND METHODS: Adult Male Sprague-Dawley rats (n=120) were randomly divided into 5 groups: sham, cerebral ischemia and reperfusion (I/R), cerebral ischemia and reperfusion plus TXL (1.6g/kg/day) (TXL1.6), TXL1.6 plus LY294002 and dimethyl sulfoxide (DMSO) (TXL1.6+LY294002), TXL1.6 plus DMSO (TXL1.6+vehicle). Prior to the grouping, TXL1.6 was selected to be the optimal dose of TXL by evaluating the neurological deficits score of five group rats (Sham, I/R, TXL0.4, TXL0.8 and TXL1.6, n=30) at 0, 1, 3, 5, and 7 days after reperfusion. Rats, being subjected to middle cerebral artery occlusion (MCAO) for 90min followed by 24h reperfusion, were the cerebral ischemia/reperfusion models. At 24h after reperfusion, cerebral infarct area was measured via tetrazolium staining and neuronal damage was showed by Nissl staining. The double staining of Terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) staining and immunofluorescence labeling with NeuN, was performed to evaluate neuronal apoptosis. Proteins involved in PI3K/Akt pathway were detected by Western blot. RESULTS: The results showed that TXL markedly improved neurological function, reduced cerebral infarct area, decreased neuronal damage, and significantly attenuated neuronal apoptosis, while these effects were eliminated by inhibition of PI3K/Akt with LY294002. We also found that TXL up-regulated the expression levels of p-PDK1, p-Akt, p-c-Raf, p-BAD and down-regulated Cleaved caspase 3 expression notably, which were partially reversed by LY294002. Additionally, the increment of p-PTEN level on which LY294002 had little effect was also detected in response to TXL treatment. CONCLUSIONS: These findings demonstrated that TXL provided neuroprotection against cerebral ischemia/reperfusion injury and neuronal apoptosis, and this effect was mediated partly by activation of the PI3K/Akt pathway.

[Ginkgo leaves tablet improved the memory quotient of patients with mild cognitive impairment: a clinical observation].

OBJECTIVE: To observe the effect of Ginkgo Leaves Tablet (GLT) on memory quotient (MQ) of mild cognitive impairment (MCI) patients. METHODS: One hundred and thirteen patients were randomly assigned to the control group (55 cases) and the treatment group (58 cases). Patients in the control group received dietetic therapy and physical exercises, while those in the treatment group additionally took GLT, 19.2 mg each time, three times daily. The treatment course was 12 months for all. The MQ of all the patients was assessed by WMS-RC before treatment,at 6-month of treatment, and 12-month of treatment. RESULTS: Compared with the control group, the improvement of MQ increased in the treatment group 0.5 and 1 year after treatment (P < 0.05). The clinical efficiency of MQ obviously increased in the treatment group (48.28% and 50.00%), showing statistical difference when compared with the control group (30.91% and 27.27%, P < 0.05, P < 0.01). There was statistical difference in added scores of recognition, regeneration, understanding, and recitation test at 6-month of treatment and 12-month of treatment between the treatment group and the control group (P < 0.05, P < 0.01). CONCLUSION: GLT was effective in improving MQ of MCI patients, especially in improving recognition, regeneration, understanding, and recitation test.

[Effects of Ginkgo biloba extract in improving episodic memory of patients with mild cognitive impairment: a randomized controlled trial].

BACKGROUND: Mild cognitive impairment is a transitional stage between normal aging and dementia. It is important in terms of recognizing memory loss in older people as well as identifying a group of individuals at high risk of developing dementia and who may benefit from preventive strategies. Ginkgo biloba extract has been shown to possess polyvalent properties, such as anti-oxidation, anti-apoptosis and anti-inflammation. Ginkgo biloba extract appears to have a neuroprotective effect against neurodegenerative diseases. OBJECTIVE: To observe the efficacy of Ginkgo biloba leaf tablet in improving episodic memory of mild cognitive impairment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a multicenter, randomized, controlled trial. The authors enrolled generally healthy, ambulatory or ambulatory-aided amnestic subjects with MCI, 60 to 85 years old, who expressed a memory complaint from Huadong Hospital, seven Community Health Centers in Shanghai, and Shanghai First Welfare Institution. A total of 120 MCI patients were randomly assigned to the Ginkgo biloba leaf tablet group (treatment group, 60 cases) and control group (60 cases). The patients in the treatment group took Ginkgo biloba leaf tablets 3 times a day, 19.2 mg each dose. The control group did not receive any intelligence-promoting or vasodilator reflex treatment except some health care. MAIN OUTCOME MEASURES: The patients were tested with nonsense picture recognition of the clinical memory scale and the logical memory test based on the Wechsler memory scale before and after treatment. RESULTS: After 6 months of treatment, the scores of the logical memory test and nonsense picture recognition were increased significantly in the treatment group (P<0.01, P<0.05), while the scores of the two tests from the control group had no statistically significant difference (P>0.05). After treatment, the positive rate of nonsense picture recognition was 55.17% in the treatment group, which was significantly higher than that of the control group at 32.73% (P<0.05). The efficacy rate of logical memory was 58.62% in the treatment group, also higher than 38.18% in the control group (P<0.05). CONCLUSION: Ginkgo biloba leaf tablet showed good efficacy in promoting episodic memory function in MCI patients.