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2000
Volume 32, Issue 14
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Based on the Maillard reaction principle of red ginseng, this study innovatively synthesized a new amino acid derivative by combining arginine with lactose through simulated synthesis and was separated and purified through repeated silica gel and polyacrylamide gel (Bio-gel P-II) column chromatography.

Purpose

The work was aimed at elucidating the synthesis of a novel amino acid derivative and investigating the intestinal protective activity of the novel amino acid derivative and possible molecular mechanism by establishing the intestinal injury model induced by cisplatin in mice.

Methods

The purity and molecular weight of the amino acid derivatives were determined to be by electrospray ionization mass spectrometry (ESI-MS). Subsequently, by establishing cisplatin (20 mg/kg)-induced intestinal injury for 10 days and IEC-6 cell model. The biochemical indexes and histopathological analysis were used to evaluate the oxidative stress and inflammatory and pathological changes of intestinal tissue in mice. The protein expression levels of p-Nuclear transcription factor-κB (p-NF-κB), cleaved caspase 3/caspase 3, cleaved caspase 9/caspase-9, Bcl-2, Bax, cytochrome C, phosphatidylinositol 3-kinase (PI3K), Protein Kinase B (Akt), p-PI3K, p-Akt were quantified through immunofluorescence staining and Western blot analysis.

Results

The new amino acid derivatives of chemical structure were identified to be 1-(arginine-Nαgroup)-1-deoxy-4-O-(β--galactopyranosyl)--fructose, named Argininyl-fructosyl-galactose (AFGA, CHNO). The results showed that pretreatment with a single AFGA dose remarkably alleviated cisplatin-evoked intestinal oxidative stress injury, and the levels of reactive oxygen species (ROS) were lessening in IEC-6 cells (<0.05, <0.01) and could effectively reduce the secretion of TNF-α and IL-1β in serum and the expression level of NF-κB protein in intestinal tissues (<0.01). Meantime, AFGA also significantly suppressed the caspase 3, caspase 9, cytochrome C and Bax protein expression in intestinal tissue in mice (<0.01), and regulated the PI3K/Akt pathway (<0.05, <0.01). Importantly, the molecular docking results of AFGA also suggested a better binding ability with the above-mentioned related target proteins.

Conclusion

The results clearly revealed AFGA as a potential multifunctional therapeutic agent with a clear protective effect against cisplatin-induced intestinal injury may be related to the PI3K/Akt signaling pathway.

© 2025 Bentham Science Publishers
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2025-10-07

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Argininyl-Fructosyl-Galactose: A Novel Amino Acid Derivative Improves Cisplatin-induced Intestinal Toxicity via Reactive Oxygen Species-mediated Apoptosis Pathway
Curr. Med. Chem. 32, 2809 (2025); https://doi.org/10.2174/0109298673259612231124070909
/content/journals/cmc/10.2174/0109298673259612231124070909
/content/journals/cmc/10.2174/0109298673259612231124070909
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  • Article Type:     Research Article
Keyword(s): anti-apoptosis; Argininyl-fructosyl-galactose; cisplatin; intestinal toxicity; reactive oxygen species; structure identification

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