Ergosta-7,9(11),22-trien-3β-ol Rescues AD Deficits by Modulating Microglia Activation but Not Oxidative Stress
Abstract
Ergosta-7,9(11),22-trien-3β-ol (EK100) was isolated from the Taiwan-specific medicinal fungus Antrodia camphorata, which is known for its health-promotion and anti-aging effects in folk medicine. Alzheimer's disease (AD) is a major aging-associated disease. We investigated the efficacy and potential mechanism of ergosta-7,9(11),22-trien-3β-ol for AD symptoms. Drosophila with the pan-neuronal overexpression of human amyloid-β (Aβ) was used as the AD model. We compared the life span, motor function, learning, memory, oxidative stress, and biomarkers of microglia activation and inflammation of the ergosta-7,9(11),22-trien-3β-ol-treated group to those of the untreated control. Ergosta-7,9(11),22-trien-3β-ol treatment effectively improved the life span, motor function, learning, and memory of the AD model compared to the untreated control. Biomarkers of microglia activation and inflammation were reduced, while the ubiquitous lipid peroxidation, catalase activity, and superoxide dismutase activity remained unchanged. In conclusion, ergosta-7,9(11),22-trien-3β-ol rescues AD deficits by modulating microglia activation but not oxidative stress.
Figures 
Figure 1
Ergosta-7,9(11),22-trien-3β-ol improved the survival and…
Figure 1
Ergosta-7,9(11),22-trien-3β-ol improved the survival and climbing of AD Drosophila. ( A ) Survival…
Figure 1 Ergosta-7,9(11),22-trien-3β-ol improved the survival and climbing of AD Drosophila. (A) Survival curve of AD Drosophila treated with different doses of ergosta-7,9(11),22-trien-3β-ol. (B) Climbing curve of AD Drosophila treated with different doses of ergosta-7,9(11),22-trien-3β-ol. CTRL denotes drug-free control, while EK denotes ergosta-7,9(11),22-trien-3β-ol (EK100).
Figure 2
Ergosta-7,9(11),22-trien-3β-ol improved ( A )…
Figure 2
Ergosta-7,9(11),22-trien-3β-ol improved ( A ) the learning ability and ( B ) one-hour…
Figure 2 Ergosta-7,9(11),22-trien-3β-ol improved (A) the learning ability and (B) one-hour memory of AD Drosophila. Error bar stands for standard error of mean, while * or ** denote p < 0.05 or 0.01 in Student’s t-test, respectively. WT denotes wildtype control. AD denotes Alzheimer’s model. AD-EK denotes the Alzheimer’s model treated with ergosta-7,9(11),22-trien-3β-ol (EK100).
Figure 3
Ergosta-7,9(11),22-trien-3β-ol decreased the expression of…
Figure 3
Ergosta-7,9(11),22-trien-3β-ol decreased the expression of ( A ) microglial activation and ( B…
Figure 3 Ergosta-7,9(11),22-trien-3β-ol decreased the expression of (A) microglial activation and (B) inflammatory markers. Error bar stands for standard error of mean, while * and *** denotes p < 0.05 and 0.001 in Student’s t-test, respectively. AD denotes Alzheimer’s model. AD-EK denotes Alzheimer’s model treated with ergosta-7,9(11),22-trien-3β-ol (EK100).
Figure 4
Ergosta-7,9(11),22-trien-3β-ol did not modulate oxidative…
Figure 4
Ergosta-7,9(11),22-trien-3β-ol did not modulate oxidative stress in an AD fruit fly model. (…
Figure 4 Ergosta-7,9(11),22-trien-3β-ol did not modulate oxidative stress in an AD fruit fly model. (A) Lipid peroxidation (MDA) assay. (B) Catalase assay. (C) SOD assay. (D) mRNA expression of oxidative stress genes. Error bar stands for standard error of mean. AD denotes Alzheimer’s model. AD-EK denotes Alzheimer’s model treated with ergosta-7,9(11),22-trien-3β-ol (EK100).