Development of resveratrol with thiolated alginate as a supplement to prevent nonalcoholic fatty liver disease (NAFLD)

Nowadays, nonalcoholic fatty liver disease is a common metabolic liver disease of all ages worldwide. However, current pharmacological and surgical treatments are accompanied with side effects and complications. EndoBarrier, a less invasive bariatric surgery, blocks the upper portion of the intestine to reduce nutrition absorption. To mimic the nutrient restriction effect of EndoBarrier, thiol-containing materials may bind to the thiol groups of the mucus with an enhanced mucoadhesive property. Here, we develop thiolated alginate with cysteine conjugation via an N-(3-dimethylaminopropyl)-N-ethylcarbodiimide/N-hydroxysuccinimide reaction. The alginate–cysteine (AC) exhibits excellent mucoadhesive properties and forms a physical barrier in the intestine to reduce absorption significantly, which was tested with both in vitro and in vivo mucoadhesive test and barrier function test. The nontoxicity property of AC was also proven with WST-1 and live and dead stain. In addition, AC demonstrates potent carrier properties of extending the release of resveratrol to improve the efficacy with the test of the transwell system in the release profile. In the long-term therapeutic evaluation, alginate cysteine with resveratrol (ACR) is orally administrated daily to mice with an methionine choline-deficient diet. The results of this in vivo study show that developed ACR could effectively alleviate fat degeneration in the liver and improve fat-related metabolic parameters in serum without hepatocellular damage and kidney dysfunction. In sum, AC was found to be mucoadhesive, reduce glucose absorption, alleviate inflammation, and decrease fatty degradation. This promising material exhibits the potential to be a supplement for nonalcoholic fatty liver disease.