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Triptolide treatment reduces Alzheimer's disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD.

Wang Q, Xiao B, Cui S, Song H, Qian Y, Dong L, An H, Cui Y, Zhang W, He Y, Zhang J, Yang J, Zhang F, Hu G, Gong X, Yan Z, Zheng Y, Wang X - Dis Model Mech (2014)

Bottom Line: Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases.We observed enhanced spatial learning performances, and attenuated Aβ production and deposition in the brain.Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of βAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.

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Treatment with triptolide had anti-oxidative effects on the brains of 5XFAD mice. (A,E) ELISA was used to detect the activity of GSH-Px in the cortex (Cor) and hippocampus (Hipp) of saline-treated wild-type mice (WT+NS), saline-treated 5XFAD mice (Tg+NS) and triptolide (T10)-treated 5XFAD mice (Tg+T10). (B,F) CAT levels in the cortex and hippocampus of the three groups of mice were measured by using ELISA. (C,G) SOD contents of the cortex and hippocampus of the three groups of mice. (D,H) The production of MDA in the cortex and hippocampus of the three groups of mice. (I,J) The protein samples of cortex or hippocampus were treated with dinitrophenyl hydrazine and subjected to western blotting. The levels of oxidative proteins were determined by using densitometry to quantify positive bands of 2,4-dinitrophenyl (DNP)-modified proteins. Actin was used as an internal control (n=6 animals per group), *P<0.05, **P<0.01, ***P<0.001 versus Tg+NS, one-way ANOVA with Tukey’s post hoc test. Conc, concentration; OD, optical density.
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f7-0071385: Treatment with triptolide had anti-oxidative effects on the brains of 5XFAD mice. (A,E) ELISA was used to detect the activity of GSH-Px in the cortex (Cor) and hippocampus (Hipp) of saline-treated wild-type mice (WT+NS), saline-treated 5XFAD mice (Tg+NS) and triptolide (T10)-treated 5XFAD mice (Tg+T10). (B,F) CAT levels in the cortex and hippocampus of the three groups of mice were measured by using ELISA. (C,G) SOD contents of the cortex and hippocampus of the three groups of mice. (D,H) The production of MDA in the cortex and hippocampus of the three groups of mice. (I,J) The protein samples of cortex or hippocampus were treated with dinitrophenyl hydrazine and subjected to western blotting. The levels of oxidative proteins were determined by using densitometry to quantify positive bands of 2,4-dinitrophenyl (DNP)-modified proteins. Actin was used as an internal control (n=6 animals per group), *P<0.05, **P<0.01, ***P<0.001 versus Tg+NS, one-way ANOVA with Tukey’s post hoc test. Conc, concentration; OD, optical density.

Mentions: We next analyzed the ability of triptolide to modulate the levels and activity of antioxidant enzymes [glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)] and the oxidative products of lipids and proteins [malondialdehyde (MDA) and protein carbonyl groups, respectively]. Treatment with triptolide prevented the decrease in the activity of GSH-Px, the expression of CAT and SOD in the cortex (Fig. 7A–C), and CAT levels in the hippocampus (Fig. 7F). By contrast, the activity of GSH-Px and the expression of SOD in the hippocampus were comparable in the three groups (Fig. 7E,G). In addition, triptolide reduced the production of the oxidative marker MDA in the cortex and hippocampus of 5XFAD mice by ~50% (Fig. 7D,H). Protein carbonyls, which represent the extent of protein oxidation, were upregulated in the brains of 5XFAD mice, and treatment with triptolide partially reversed these effects (Fig. 7I,J). Triptolide therefore increased the activities of anti-oxidative enzymes and subsequently reduced the production of oxidative markers in the brains of 5XFAD mice.


Triptolide treatment reduces Alzheimer's disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD.

Wang Q, Xiao B, Cui S, Song H, Qian Y, Dong L, An H, Cui Y, Zhang W, He Y, Zhang J, Yang J, Zhang F, Hu G, Gong X, Yan Z, Zheng Y, Wang X - Dis Model Mech (2014)

Treatment with triptolide had anti-oxidative effects on the brains of 5XFAD mice. (A,E) ELISA was used to detect the activity of GSH-Px in the cortex (Cor) and hippocampus (Hipp) of saline-treated wild-type mice (WT+NS), saline-treated 5XFAD mice (Tg+NS) and triptolide (T10)-treated 5XFAD mice (Tg+T10). (B,F) CAT levels in the cortex and hippocampus of the three groups of mice were measured by using ELISA. (C,G) SOD contents of the cortex and hippocampus of the three groups of mice. (D,H) The production of MDA in the cortex and hippocampus of the three groups of mice. (I,J) The protein samples of cortex or hippocampus were treated with dinitrophenyl hydrazine and subjected to western blotting. The levels of oxidative proteins were determined by using densitometry to quantify positive bands of 2,4-dinitrophenyl (DNP)-modified proteins. Actin was used as an internal control (n=6 animals per group), *P<0.05, **P<0.01, ***P<0.001 versus Tg+NS, one-way ANOVA with Tukey’s post hoc test. Conc, concentration; OD, optical density.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257007&req=5

f7-0071385: Treatment with triptolide had anti-oxidative effects on the brains of 5XFAD mice. (A,E) ELISA was used to detect the activity of GSH-Px in the cortex (Cor) and hippocampus (Hipp) of saline-treated wild-type mice (WT+NS), saline-treated 5XFAD mice (Tg+NS) and triptolide (T10)-treated 5XFAD mice (Tg+T10). (B,F) CAT levels in the cortex and hippocampus of the three groups of mice were measured by using ELISA. (C,G) SOD contents of the cortex and hippocampus of the three groups of mice. (D,H) The production of MDA in the cortex and hippocampus of the three groups of mice. (I,J) The protein samples of cortex or hippocampus were treated with dinitrophenyl hydrazine and subjected to western blotting. The levels of oxidative proteins were determined by using densitometry to quantify positive bands of 2,4-dinitrophenyl (DNP)-modified proteins. Actin was used as an internal control (n=6 animals per group), *P<0.05, **P<0.01, ***P<0.001 versus Tg+NS, one-way ANOVA with Tukey’s post hoc test. Conc, concentration; OD, optical density.
Mentions: We next analyzed the ability of triptolide to modulate the levels and activity of antioxidant enzymes [glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)] and the oxidative products of lipids and proteins [malondialdehyde (MDA) and protein carbonyl groups, respectively]. Treatment with triptolide prevented the decrease in the activity of GSH-Px, the expression of CAT and SOD in the cortex (Fig. 7A–C), and CAT levels in the hippocampus (Fig. 7F). By contrast, the activity of GSH-Px and the expression of SOD in the hippocampus were comparable in the three groups (Fig. 7E,G). In addition, triptolide reduced the production of the oxidative marker MDA in the cortex and hippocampus of 5XFAD mice by ~50% (Fig. 7D,H). Protein carbonyls, which represent the extent of protein oxidation, were upregulated in the brains of 5XFAD mice, and treatment with triptolide partially reversed these effects (Fig. 7I,J). Triptolide therefore increased the activities of anti-oxidative enzymes and subsequently reduced the production of oxidative markers in the brains of 5XFAD mice.

Bottom Line: Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases.We observed enhanced spatial learning performances, and attenuated Aβ production and deposition in the brain.Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of βAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.

Show MeSH
Related in: MedlinePlus