The new coumarin compound Bis 3 ameliorates cognitive disorder and suppresses brain-intestine-liver systematic oxidative stress in high-fat diet mice.

Abstract

High-fat diet (HFD)-induced systemic oxidative damage is critical to the pathological process of obesity and is associated with energy metabolism and cognitive disorders. In our previous research, the coumarin derivative Bis 3 was shown to improve neurological disorders as a potent free radical scavenger. In this study, a 12-week high-fat diet model was established, and mice were randomly divided into 3 groups: standard diet, high-fat diet, and high-fat diet with Bis 3 treatment. Our results demonstrated that Bis 3 attenuated body weight gain and inhibited the development of insulin resistance in high-fat diet-fed mice. Bis 3 protected against high fat-induced intestinal barrier integrity damage and lipid content disorder. HFD-induced hepatocyte lipid metabolism disorder and hepatocyte damage were also alleviated by Bis 3. Moreover, the results of cognitive tests indicated that Bis 3 attenuated high fat-induced cerebral dysfunction, such as cognitive disorders. Importantly, Bis 3 simultaneously ameliorated oxidative stress in the digestive and central nervous systems. These findings suggest that Bis 3 protects against systematic oxidative stress in HFD-induced obese mice, balancing insulin resistance, lipid metabolic disorders, and cognitive disorders through its antioxidative effects, indicating that Bis 3, a novel free radical scavenger, might represent a new therapeutic strategy for high fat-induced chronic systemic redox imbalance.

• Authors: Jun Wang, Wentong Zhang, Mingkai Li, Xia Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 137 Pg. 111293 (May 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 33485120 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Antioxidants
• Blood Glucose
• Coumarins

Topics

• Animals
• Antioxidants (pharmacology)
• Behavior, Animal (drug effects)
• Blood Glucose (drug effects, metabolism)
• Brain (drug effects, metabolism, physiopathology)
• Cognition (drug effects)
• Cognition Disorders (etiology, metabolism, prevention & control, psychology)
• Coumarins (pharmacology)
• Diet, High-Fat
• Disease Models, Animal
• Insulin Resistance
• Intestines (drug effects)
• Lipid Metabolism (drug effects)
• Liver (drug effects, metabolism)
• Locomotion (drug effects)
• Male
• Mice, Inbred C57BL
• Morris Water Maze Test (drug effects)
• Oxidative Stress (drug effects)
• Mice