PTP1B inhibitory activity and molecular docking analysis of stilbene derivatives from the rhizomes of Rheum undulatum L

Stilbene derivatives, the principal constituent of Rheum undulatum L., are known to have a wide range of biological activities, such as anti-allergic, anti-diabetic, antioxidant, and anti-inflammatory activities. A phytochemical study on the methanol extract of Korean rhubarb (R. undulatum L.) led t...

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Published in:Fitoterapia 2018-11, Vol.131, p.119-126
Main Authors: Ha, Manh Tuan, Park, Dong Hwa, Shrestha, Srijan, Kim, Minji, Kim, Jeong Ah, Woo, Mi Hee, Choi, Jae Sue, Min, Byung Sun
Format: Article
Language:English
Subjects:
Antioxidants
Data processing
Derivatives
Diabetes mellitus
Flavonoids
Flowers & plants
Inflammation
Inhibition
Molecular docking
Phytochemicals
Piceatannol
Polygonaceae
Protein tyrosine phosphatase 1B
Protein-tyrosine-phosphatase
Proteins
Rheum undulatum
Rhizomes
Rhubarb
Stilbene
Stilbenes
Tyrosine
Ursolic acid
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Summary:Stilbene derivatives, the principal constituent of Rheum undulatum L., are known to have a wide range of biological activities, such as anti-allergic, anti-diabetic, antioxidant, and anti-inflammatory activities. A phytochemical study on the methanol extract of Korean rhubarb (R. undulatum L.) led to the isolation of nine stilbene derivatives (1–9) and one flavonoid (10). All structures were elucidated based on a comprehensive analysis of spectroscopic data. Compound 1 (5-methoxy-cis-rhapontigenin) was elucidated as a new compound, while compound 2 (5-methoxy-trans-rhapontigenin) was isolated from a natural source for the first time. Among the isolated compounds, stilbene derivatives (7–9) showed a strong inhibitory effect on protein tyrosine phosphatase 1B (PTP1B) with IC50 values ranging from 4.25 to 6.78 μM, which was significantly higher than that of the positive control, ursolic acid (IC50 = 11.34 μM). Furthermore, for the first time, kinetic analysis and molecular docking simulations were performed in order to understand the inhibition type as well as the interaction and binding mode of the active stilbenes (7–9) with PTP1B. Our results showed that the types of PTP1B inhibition were noncompetitive for ɛ-viniferin (8) and mixed for piceatannol (7) and δ-viniferin (9). Docking simulations of these stilbenes demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B. [Display omitted]
ISSN:0367-326X
1873-6971
DOI:10.1016/j.fitote.2018.10.020