Curcumin ameliorates insulin signalling pathway in brain of Alzheimer's disease transgenic mice.

Deficits in glucose, impaired insulin signalling and brain insulin resistance are common in the pathogenesis of Alzheimer's disease (AD); therefore, some scholars even called AD type 3 diabetes mellitus. Curcumin can reduce the amyloid pathology in AD. Moreover, it is a well-known fact that curcumin has anti-oxidant and anti-inflammatory properties. However, whether or not curcumin could regulate the insulin signal transduction pathway in AD remains unclear. In this study, we used APPswe/PS1dE9 double transgenic mice as the AD model to investigate the mechanisms and the effects of curcumin on AD. Immunohistochemical (IHC) staining and a western blot analysis were used to test the major proteins in the insulin signal transduction pathway. After the administration of curcumin for 6 months, the results showed that the expression of an insulin receptor (InR) and insulin receptor substrate (IRS)-1 decreased in the hippocampal CA1 area of the APPswe/PS1dE9 double transgenic mice, while the expression of phosphatidylinositol-3 kinase (PI3K), phosphorylated PI3K (p-PI3K), serine-threonine kinase (AKT) and phosphorylated AKT (p-AKT) increased. Among the curcumin groups, the medium-dose group was the most effective one. Thus, we believe that curcumin may be a potential therapeutic agent that can regulate the critical molecules in brain insulin signalling pathways. Furthermore, curcumin could be adopted as one of the AD treatments to improve a patient's learning and memory ability.

[Neuroprotective effect of curcumin to Aß of double transgenic mice with Alzheimer's disease].

OBJECTIVE: To observe the changes in Aß40, Aß42 and ADDLs in brains of 3 month-old APPswe/PS1dE9 double transgenic mice after six-month intervention with curcumin, in order to discuss the neuroprotective effect of curcumin. METHOD: APPswe/PS1dE9dtg mice were randomly divided into the model group, the Rosiglitazone group (10 mg x kg(-1) x d(-1)) and curcumin high (400 mg x kg9-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dosage groups, with C57/BL6J mice of the same age and the same background in the normal control group. After 6 months, the immunohistochemical staining (IHC) and the Western blot method were used to observe the changes in positive cell of Aß40, Aß42 and ADDLs in hippocampal CA1 area, their distribution and protein expressions. RESULT: Both of the immunohistochemical staining and the Western blot method showed more positive cell of Aß40, Aß42 and ADDLs in hippocampal CA1 area and higher protein expressions in the model group than the normal group (P < 0.01). IHC showed a lower result in the Rosiglitazone group than the model group (P < 0.05), while Western blot showed a much lower result (P < 0.01). The number of Aß40, Aß42 and ADDLs positive cells and the protein expressions decreased in the curcumin high group, the medium group showed a significant decrease (P < 0.01), and the low dose group also showed reductions in the protein expressions of Aß40 and Aß42. CONCLUSION: The six-month intervention with curcumin can significantly reduce the expressions of hippocampal Aß40, Aß42 and ADDLs in brains of APPswe/PS1dE9 double transgenic mice. Whether curcumin can impact Aß cascade reaction by down-regulating expressions of Aß40, Aß42 and ADDLs and show the neuroprotective effect needs further studies.

[Effect of curcumin on hippocampal IRS-1 and p-IRS-1 expressions in APP/PS1 double transgenic mice].

OBJECTIVE: To observe the effect of curcumin on the expressions of insulin receptor substrate-1 (IRS-1) and phosphated insulin receptor substrate-1 (p-IRS-1I) in APP/PS1 double transgenic mice of the AD model. METHOD: Three-month-old APP/ PSI double transgenic mice were randomly divided into the model group, the positive rosiglitazone control group and curcumin high (400 mg . kg-1 . d-1), medium (200 mg . kg-1 . d-1) and low (100 mg . kg-1 . d-1) dose groups. The normal group was composed of non-transgenic mice under the same background. After they were orally administered for three months, they were detected with immunohistochemistry, Western blot and RT-PCR. RESULT: According to IRS-1 and p-IRS-1 immumohistochemical staining, the expression of IRS-1 positive cells in hippocampus CA1 area in model mice was significantly higher than that of the normal control group (P<0. 01). Compared with the model group, the number of IRS-1 positive cells in hippocampus CA1 area decreased (P <0. 05 or P <0. 01) and the number of p-IRS-1 positive cells in hippocampus CA1 area increased in all of curcumin intervention groups. Western blot results were consistent with IRS-1 and p-IRS-1 protein expressions and immunohistochemistry results. RT-PCR test showed opposite IRS-1 mRNA expression results with immunohistochemistry and Western blot results. CONCLUSION: Curcumin can recover increased IRS-1 and decreased p-IRS-1 in hippocampus of APP/PS1 double transgenic mice, increase IRS-1 mRNA expression, and improve the insulin-signaling transduction in APP/PS1 double transgenic mice. This suggests that curcumin can regulate the insulin-signaling transduction mechanism and show an anti-AD effect.

[Effects of curcumin on expression of PI3K and p-pI3K in hippocampus of AD mice].

OBJECTIVE: To observe the effect of curcumin on the expression of PI3K (phosphatidylinositol-3-kinase, PI3K) and p-P3 K (phosphated phosphatidylinositol-3-kinase, p-PI3K) in the hippocampus of Alzheimer's disease (AD) model (APP/PS1 double transgenic) mice. METHOD: A total of 60 three-month-old APP/PS1 double transgenic mice were randomly divided into model group, rosiglitazone group(10 mg . kg-1 . d-1) and curcumin large(400 mg . kg-1 . d-1), medium(200 mg- kg-1 . d-1) and small(100 mg . kg-1 . d-1) dose group. Twelve C57BL/6J mice in the same age and genetic background as APP/PS1 double transgenic mice were used as normal control group. All the 6 groups of mice were intragastrically administered for 3 months. After 3 months, the expression of PI3K and p-PI3K were detected by immunohistochemistry and Western blot. RESULT: The expression of PI3K and p-PI3K positive cells in hippocampus CA1 region significantly decreased in model group compared with normal control group (P < 0. 05) , while compared with model group, PI3K and p-PI3K positive cells of all the curcumin intervention groups increased to varying degrees in hippocampus CA1 region,especially the middle dose group(P <0. 01). Besides,Western blot results of the curcumin high dose group were also increased obviously (P <0. 05). CONCLUSION: Curcumin can recover the decreased PI3K and p-PI3K and improve the insulin-signaling transmission in the hippocampus of APP/PS1 double transgenic mice. The mechanism of curcumin maybe by regulating the insulin signal transduction to treat AD.

[Dynamic effect of curcumin on urine concentration of neuronal thread protein in AD mice].

OBJECTIVE: Through the dynamic detection of the concentration change of the urine Alzheimer-associated neuronal thread protein (AD7C-NTP) in the curcumin treated Alzheimer's disease (AD) model (APP/PS1 double transgenic) mice, the therapeutic effect of curcumin in AD was determined. METHOD: Thirty three-month-old APP /PS1 double transgenic mice were randomly divided into 5 groups, 6 in each group, the model group, rosiglitazone group(10 mg . kg-1 . d-1) , high(400 mg . kg -1 . d-1) , medium(200 mg . kg-1. d-1) and low(100 mg . kg-1 . d-1) dose curcumin groups. Six C57BL/6J mice in the same age and genetic background were used as normal control group. All the 6 groups of mice were intragastrically administered for 6 months. Urine samples were collected on 4 month, 5 month and 6 month after intragastric administration, respectively. The changes of urinary AD7C-NTP concentration were detected by enzyme-linked immunosorbent assay (ELISA). RESULT: The concentration of AD7C-NTP of each group was compared at the same time point, the concentration of model group is higher than normal control group (P <0.05) ; the concentration of other groups is lower than model group. The concentration of high curcumin dose group with 4 months treatment, has no statistical difference compared with model group. The AD7C-NTP concentration of each group was elevated with the age growth, and all concentrations of the treatment groups were lower than the model group at the same period. With the treatment of 4, 5 and 6 months, the concentration of the normal control group has significant difference with the treatment groups(P <0. 01). There have no statistical difference between all the groups with the treatment of 6 months compared with 5 months. CONCLUSION: With the progression of the disease in AD mice, there are fluctuations in urinary AD7C-NTP concentration, the compound curcumin from traditional Chinese medicine can delay the progression of AD.

[Effect of curcumin on expression of AKT and p-AKT in hippocampus CA1 area of App/PS1 double transgenic mice].

OBJECTIVE: To observe the effect of curcumin on the expressions of AKT (serine-threonine kinase, AKT, also known as PKB) and p-AKT (phosphated serine-threonine kinase, p-AKT) in APP/PS1 double transgenic mice of the AD model. METHOD: Three-month-old APP/PS1 double transgenic mice were randomly divided into the model group, the rosiglitazone (10 mg kg-1 . d-1) group, and high (400 mg . kg-1 d-1), medium (200 mg . kg-1 d-1) and low (100 mg kg-1 d-1) dosecurcumin groups. Non-transgenic mice of the same age and background were selected as the control group ( n = 12). After all of the six groups were intragastrically administered for consecutively three months, the protein expressions of AKT and p-AKT in hippocampus CA1 area were detected by immunohistochemistry and Western blot. RESULT: The results of immunohistochemistry showed that the expression of AKT and p-AKT positive cells in hippocampus CA1 area significantly decreased in the model group (P <0. 05 and P < 0. 01). Compared with the model group, AKT and p-AKT positive cells of hippocampus CA1 area increased obviously in the rosiglitazone group and high and medium dose curcumin group (P <0.05 or P <0.01) ,especially the medium dose group (P <0.01). The results of Western blot were consistent with that of immunohistochemistry. CONCLUSION: Curcumin can recover the decreased AKT and p-AKT cells in hippocampus CAl area of APP/PS1 double transgenic mice of the AD model, suggesting that curcumin may regulate AKT and its phosphorylation process, as well as PI3K/AKT insulin signal transduction pathway, and show the anti-AD effect.

[An experiment study of protection and treatment of Kudan granule on rats of pulmonary fibrosis induced by pinyangmycin].

OBJECTIVE: To explore the protection and treatment effects of Kudan granule on rats of pulmonary fibrosis induced by pinyangmycin. METHOD: In asepsis condition, rat was anaesthetized by 3.5% chloral hydrate, inserted the needle above the bifurcation of trachea and injecting 5 mg x kg(-1) pinyangmycin normal saline solution. RESULT: For model-group rats, after injecting pinyangmycin at 7, 14, 28, 56 days, there were mass inflammation cell infiltration at pulmonary alveoli and interstitial, the pulmonary alveolar wall and interstitial thickened obviously, and the pulmonary interval broadened distinctly. The structure of collagen fiber was destroyed, and the pulmonary alveoli disappeared. By Masson dyeing, there were hunk collagen fiber and the consolidation of lung had come into being. Compared with the model group, the rats of Kudan granule big-dose group, at 7, 14, 28, 56 days after injecting pinyangmycin, there were still much inflammation cell infiltration at pulmonary alveoli and interstitial, pulmonary interstitial edema and spotty necrosis, thickened alveolar wall, broadened pulmonary interval, and much collagen fiber in pulmonary interstitial, but there was not bunk the consolidation of lung. The curative effect of Kudan granule small-dose group was not better than that of Kudan granule big-dose group, because there were still bunk collagen fiber and the consolidation of lung in pulmonary interstitial. Although the destroyed area was more than 50%, it was better than that of the model-group. CONCLUSION: The big-dose Kudan granule show the better function of protection and treatment for pulmonary fibrosis of rats induced by pinyangmycin.

[Effect and mechanism of bishudiwan(BSDW) against allergy].

OBJECTIVE: To investigate the effect and mechanism of BSDW on the model of allergic rhinitis and the model of guinea pigs by histamine shocking in guinea pigs. METHOD: Using the model of allergic rhinitis in guinea pigs caused by 10% TDI, we observed the effect of BSDW on physiological and pathological symptoms of allergic rhinitis in guinea pigs, the effect of the levels of serum IgE and serum and nasal histamine. Using the model of guinea pigs by histamine shocking, we observed the effect of BSDW on physiological symptoms in guinea pigs. RESULT: BSDW significantly relieved the pathological symptoms of allergic rhinitis in guinea pigs, alleviated the hyperplasia of columnar epithelium, decreased the number of monocyte and eosinocyte compared with the model group. It also reduced the levels of serum IgE, and decreased the release of serum and nasal histamine. BSDW significantly prolonged the occurent time of gasping, eclampsia and death caused by shock, reduced the times of gasping in the model of guinea pigs by histamine shocking. CONCLUSION: BSDW has significant effect against allergy. The mechanism relates to its effects of decreasing the levels of serum IgE and inhibiting the release of serum and nasal histamine.