Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 / 中国天然药物

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aβ

Separation and Extraction of Total Flavonoids from Dendrobium nobile Leaves and Study on Its Anti-Alzheimer's Disease Activity in vitro / 中国药房

OBJECTIVE: To separate and isolate total flavonoids from Dendrobium nobile leaves, and to investigate its anti-Alzheimer's disease (AD) activity in vitro. METHODS: Total flavonoids were obtained by ultrasonic extraction method and extracted by chloroform, ethyl acetate and butyl alcohol after the obtained extract was dispersed with water. Qualitative analysis was carried out with color reaction and TLC. The content of total flavonoids in extracts was analyzed quantitatively by Aluminum nitrate-sodium nitrite method. Antioxidant activity of extract was investigated by DPPH radical scavenging assay; the inhibitory effect of each extract on Aβ42 protein aggregation was investigated by Thioflavin T assay. Metals (Cu2+, Fe3+, Zn2+) chelating property was studied by UV-vis spectrum scanning to investigate the anti-AD activity in vitro. RESULTS: The flavonoids were found in ethyl acetate, butyl alcohol and aqueous extracts, and their flavonoids contents were 0. 03, 0. 12, 0. 05 mg/mL, respectively. IC50 of three extracts to DPPH free radicals were 0. 021, 0. 011, 0. 013 mg/mL. Inhibitory rates of them to Aβ42 protein aggregation were 43. 77％, 52. 28％, 38. 42％, respectively. Three extracts exerted metal chelating ability which was best in Cu2+. CONCLUSIONS: The total flavonoids from D. nobile leaves have good antioxidant activities, Aβ42 aggregation inhibitory activities and metal chelating activity, show certain anti-AD activity in vitro especially in butyl alcohol extract.

Effect of controlled low threshold blood pressure on the expression of A β42 and p-Tau-181 protein in cerebrospinal fluid and cognition after operation in aged rats / 实用医学杂志

Objective To investigate the effects of different duration hypotension thresholds on p-Tau-181 and Aβ-42 protein expression and cognition in rats. Methods Thirty-nine healthy male SD rats were randomly di-vided into 4 groups:the control group(group C,n=9),the hypotension group(groupA1、A2、A3 ,n=10). The blood pressure of groupA1、A2、A3 was measured in different time of 2 h、4 h、6 h ,for 5 days. The antihyperten-sive group of mean arterial pressure(MAP)were maintained in the 50~55 mmHg safe range. Morris water maze was used to detect the spatial learning and memory ability of rats. The levels of Aβ42 and p-Tau-181 were detected by ELISA. Results There was no significant difference in mortality of rats in each group (P > 0.05). Compared with the group C,the escape latency and swimming distance of A2 group and A3 group were increased(P<0.05). In 3~7 days after operation,the cerebrospinal fluid P-Tau-181 and Aβ42 protein expression increased in the A2 group and A3 group compared with the A1 group(P<0.05). The escape latency and swimming distance of the A2 group and the A3 group were significantly longer than those in the control group. Aβ42 and p-Tau-181 were signifi-cantly increased in A3 group(P < 0.05). Compared with the A2 group,the increase of Aβ42 and p-Tau-181 in the A3 group was not significant(P<0.05). Conclusion Long-term controlled hypotension may lead to postoper-ative cognitive dysfunction which may relate to the increase of Aβ42 and p-Tau-181 protein expression.

Overexpression of N141I PS2 increases γ-secretase activity through up-regulation of Presenilin and Pen-2 in brain mitochondria of NSE/hPS2m transgenic mice / 한국실험동물학회지

Alzheimer's disease (AD) is known to induce alterations of mitochondrial function such as elevation of oxidative stress and activation of apopotosis. The aim of this study was to investigate the effects of human Presenilin 2 mutant (hPS2m) overexpression on the γ-secretase complex in the mitochondrial fraction. To achieve this, alterations of γ-secretase complex expression and activity were detected in the mitochondrial fraction derived from brains of NSE/hPS2m Tg mice and Non-Tg mice. Herein, the following were observed: i) overexpression of the hPS2m gene significantly up-regulated the deposition of Aβ-42 peptides in the hippocampus and cortex of brain, ii) overexpression of hPS2m protein induced alterations of γ-secretase components such as main component protein and activator protein but not stabilization-related proteins, iii) changes in γ-secretase components induced by overexpression of hPS2m protein up-regulated γ-secretase activity in the mitochondrial fraction, and iv) elevation of γ-secretase activity induced production of Aβ-42 peptides in the mitochondrial fraction. Based on these observations, these results indicate that alteration of γ-secretase activity in cells upon overexpression of hPS2m is tightly linked to mitochondrial dysfunction under the specific physiological and pathological conditions of AD.

Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection / 한국실험동물학회지

To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Aβ-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Aβ-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Aβ-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75NTR expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis.

Significance and detection of Aβ42 and P-tau levels in CSF of patients with mild cognitive impairment / 实用医学杂志

Objective To investigate Aβ42 and P-tau levels in cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI). Methods CSF of 25 cases of MCI and 14 cases of cognitively normal (CN) were investigated. The CSF levels of Aβ42 and P-tau were detected by ELISA method. Correlation analysis was used to analyze the correlation between P-tau level and MMSE score in MCI. Results The CSF level of Aβ 42 was higher and P-tau was lower in MCI than CN group(P<0.05). P-tau level in MCI was also negatively correlated with MMSE score (P<0.05). Conclusion Aβ42 and P-tau levels in CSF may be valuable biological markers in the diagnosis of MCI. P-tau level in CSF of MCI may be related to the severity of cognitive impairment.

Effect of Tibet-medicine Ratanasampil on serum β-amyloid protein and inflamatory cytokine levels in patients with Alzheimer's disease / 中华老年医学杂志

Objective To study the effect of ratanasampil (RNSP) which is Traditional Tibetan Medicine on the levels of serum β-amyloid protein, interleukin and tumor necrosis factor alpha (TNF-α) in patients with mild to moderate Alzheimer's disease (AD). Methods One hundred AD patients were divided into two groups in randomized controlled study, including treatment group (RNSP 1 g/d) and control group (piracetam 2.4 g/d). The treatment lasted 12 weeks. The Mini Mental State Examination (MMSE), Alzheimer' s disease Assessment Scale-cognitive subscale (ADAS-cog) and Activity of Daily Living Scale (ADLs) were taken to evaluate the efficacy. Serum levels of amyloid peptides (Aβ40 and Aβ42 ) were measured by ELISA assay. The radioimmunologic assay was used to determine the serum levels of IL-1β, IL-2, IL-6, IL-8 and TNF-α. Results The scores of MMSE, ADAS-cog and ADL significantly improved at 12 weeks after RNSP treatment (P＜0.01, 0.01, 0.05, respectively), while had no significant changes in piracetam group (P＜0.05).The levels of TNF-α, IL-1β, IL-6 and Aβ42 were significantly lower in RNSP group than in Piracetam group (P＜0.01). There was a decrease trend of the Aβ42/Aβ40 ratio at 12 weeks after RNSP treatment (P＜0. 05, P＜0.01 ). The serum Aβ42 level had strong correlations with TNF-α, IL-1 β and IL-6. There were no significant differences in Aβ40 and IL-8 between RNSP group and piracetam group. No obvious drug side effect happened on the groups. Conclusions The reductions of serum TNF-α, IL-1β and IL-6 levels after RNSP treatment may lead to decrease of Aβ42 production in AD patients. RNSP may decrease the Aβ42/Aβ40 ratio and slow down the progress of AD. It may improve the learning and memory ability in treating patients with mild to moderate AD and is well tolerated and safe.

Age-related changes of the expression of p21-activated kinase in hippocampus in an APP/PS1 transgenic mice model of Alzheimer's disease / 神经解剖学杂志

It has been known that the Alzheimer's disease(AD)is related closely with a synaptic failure,and the p21-activated kinase(PAK)is well documented to play an important role in the regulation of the synaptie functions.However,the relationship between thePAK and the pathology of AD is unclear.In the present study,we examined the expressions of the PAK3(one subtype ofPAK),phospho-rylated-PAK(pPAK) and β-amyloid42(Aβ42,β-amyloid with 42 peptides)in an APP/PS1 double transgenie mouse model of AD andthe morphologies of geurOtlS in the hippocampus at different ages.The Western Blot results showed that the expression of PAK remainedunchanged,while,the expression of pPAK decreased largely at the age of 32 weeks and further decreased significantly with aging in thehippocampus of the APP/PS1 transgenic mouse.A1342 levels in the hippocampus were detected to increase as early as the age of 22 weeks,and kept the increase to continue with aging.The morphological results showed no obvious neuron loss in the sections of Nissl staining,while serious distonion and disorder of the dendrites of the hippocampal neurons were observed on the sections of Gelgi staining in theAPP/PS1 transgenic mouse.The present results suggested that it seemed something wrong in the processes of phospholization of PAK,butnot in the expression of the PAK itself;the toxic Aβ42 might affect the PAK in its phospholization,which in turn directly influence thedendritic development in the hippocampal neurons and cause the dendrites distorting and disordering.