title: IAPP aggregation and cellular toxicity are inhibited by 1,2,3,4,6-penta-O-galloyl-β-D-glucose.
abstract: The polyphenol, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) has been found to exhibit a host of positive pharmacologic activities, including anti-cancer and anti-diabetic. Little is known about the mode of action of PGG in yielding these positive activities. We show here that PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the toxic effects of IAPP oligomeric intermediates. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind thioflavin T. Atomic force microscopy revealed that PGG prevented amyloid-based fiber formation under rigorous conditions conducive to forming IAPP aggregates. PGG was also found to protect PC12 rat cells from toxic IAPP. PGG was compared to the known amyloid inhibitors (and structural relatives); tannic acid and gallic acid. In every test, PGG was far superior to tannic and gallic acids at inhibiting amyloid aggregation. These results indicate that PGG is a potent inhibitor of IAPP amyloid aggregation and a potential lead molecule for development of an amyloid inhibiting therapeutic.
authors: Department of Chemistry and Biochemistry, Loyola Marymount University, Los Angeles, CA 90045, USA.
authors: Edward
authors: E
authors: Bruno
authors: Catalina
authors: C
authors: Pereira
authors: Karla P
authors: KP
authors: Roman
authors: Marisa
authors: M
authors: Takiguchi
authors: Pei-Yu
authors: PY
authors: Kao
authors: Luiza A
authors: LA
authors: Nogaj
authors: David A
authors: DA
authors: Moffet
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D002470:Cell Survival / Q000187:drug effects; D005707:Gallic Acid / Q000494:pharmacology; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018625:Microscopy, Atomic Force; D016716:PC12 Cells; D051381:Rats; D013050:Spectrometry, Fluorescence; D013634:Tannins / Q000494:pharmacology; D013844:Thiazoles
chemical_list: D052160:Benzothiazoles; D047348:Hydrolyzable Tannins; D058228:Islet Amyloid Polypeptide; D013634:Tannins; D013844:Thiazoles; C009462:thioflavin T; C435084:pentagalloylglucose; D005707:Gallic Acid