Tubuloside B inhibits Aβ1-42 fibrillization and alleviates amyloid-induced cytotoxicity
10.16438/j.0513-4870.2024-0531
- VernacularTitle:管花苷B抑制Aβ1-42淀粉样纤维化并降低其细胞毒性的研究
- Author:
Di ZHANG
;
Juan-li ZHANG
;
Ai-dong WEN
;
Jing-wen WANG
- Publication Type:Research Article
- Keywords:
tubuloside B;
Alzheimer's disease;
amyloid β-protein;
fibrillization;
inhibition
- From:
Acta Pharmaceutica Sinica
2025;60(1):96-104
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the inhibitory effect of tubuloside B (Tub B) on amyloid β-protein (Aβ), and analyse the potential mechanism. A model of amyloid fibril was established by incubation of Aβ1-42 in vitro. Thioflavin-T (ThT), Congo red (CR), 8-anilino-1-naphthene sulfonic acid (ANS) staining and transmission electron microscopy (TEM) were applied to detect the suppression of Tub B on the formation of Aβ1-42 fibril. Circular dichroism (CD) was used to analyse the regulatory effect of Tub B on the secondary structure of Aβ1-42. 3-(4,5-Dimethyl-2-thiazole) -2,5-diphenyltetrazolium bromide (MTT) and red blood cell hemolysis experiments were used to investigate the attenuation of Tub B on Aβ1-42 induced cytotoxicity. 2',7'-Dichlorofluorescin diacetate (DCFH-DA) staining was used to assess the expression of intracellular reactive oxygen species (ROS) induced by Aβ1-42. And molecular docking experiment was used to explore the interaction between Tub B and Aβ1-42. The results indicated that Tub B could inhibit Aβ1-42 fibrillization in a certain extent, which retarded the structural transition of α-helix to β-sheet of Aβ1-42, hampered the exposure of hydrophobic regions, and attenuated amyloid-induced cytotoxicity and hemolysis. In summary, Tub B can prevent the formation of Aβ1-42 amyloid fibril, which may be related to its antioxidant activity and hydrogen bonding and hydrophobic interactions with protein molecules. All animal experiments were approved by the Experimental Animal Research Center of Air Force Medical University (No. 20190051).
