Herbacetin Inhibits Human Fructose 1,6-Bisphosphatase Among a Panel of Chromone Derivatives and Pyrazoles, Demonstrating Positive Effects on Insulin-Resistant HepG2 Cells

• Type: Article in International Scientific Journal
• Date: 2024

Authors

Rocha, S (Author) Other; Vicente, B (Author) Other; Proença, C (Author) Other; Silva, VLM (Author) Other; Silva, AMS (Author) Other; Corvo, ML (Author) Other; Eduarda Fernandes (Author) FFUP; Freitas, M (Author) Other

Journal

Title: Chemical Biology and Drug Design

Vol. 104

ISSN: 1747-0277

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 0 Citations

Scopus

Other information

Authenticus ID: P-017-HA2

DOI: 10.1111/cbdd.70017

Abstract (EN): In patients with type 2 diabetes mellitus (DM), excessive gluconeogenesis is considered a major contributor to hyperglycemia. Therefore, targeting fructose 1,6-bisphosphatase (FBPase), a key regulatory enzyme involved in gluconeogenesis, has gained interest as a potential therapeutic target for managing DM. In this study, a library of 42 structurally-related chromone derivatives (including flavonoids, 2-styrylchromones, and 2-(4-arylbuta-1,3-dien-1-yl)chromones, named as 2-styrylchromone-related derivatives), as well as 4- and 5-styrylpyrazoles, were tested against human FBPase using a noncellular microanalysis screening system. Herbacetin, 3,4 ',5,7,8-pentahydroxyflavone, inhibited FBPase activity with an IC50 value of 6.4 +/- 0.7 mu M. The effects of herbacetin were also explored using an insulin-resistant human hepatocellular carcinoma cell line (HepG2 cells). The results showed that herbacetin significantly decrease insulin resistance by promoting the phosphorylation of protein kinase B (Akt), and exhibited a capacity to ameliorate inflammation, evidenced by the modulation of the inhibitor of kappa B alpha (I kappa B alpha). This study provides important considerations for the design of novel FBPase inhibitors. Furthermore, it indicates a preliminary potential of herbacetin's dual action in improving insulin resistance and decreasing inflammation, suggesting the need for further investigation of this compound for addressing the complexities of type 2 DM management.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15