Wei Liu, Yi-nan Zheng, Shuang Jiang, Shen Ren, Shan Tang, Jing Zhang, Zi Wang, Wei Li

Argininyl-Fructosyl-Galactose: A Novel Amino Acid Derivative improves Cisplatin-induced Intestinal Toxicity via Reactive Oxygen Species- mediated Apoptosis Pathway

  • Pharmacology
  • Molecular Medicine
  • Drug Discovery
  • Biochemistry
  • Organic Chemistry
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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. background: Based on the Maillard reaction principle of red ginseng (Panax ginseng C.A. Meyer) 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. objective: In recent years, there has been growing interest in the development of amino acid derivatives because of the increasingly prominent application of MR in newly-type functional foods 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 in vivo 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. method: 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, establishing cisplatin-induced intestinal injury in vivo and IEC-6 cell model Results: The new amino acid derivatives of chemical structure were identified to be 1- (arginine-Nαgroup)-1-deoxy-4-O-(β-D-galactopyranosyl)-D-fructose, named Argininylfructosyl- galactose (AFGA, C18H34N4O12). 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 (p<0.05, p<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 (p<0.01). Meantime, AFGA also significantly suppressed the caspase 3, caspase 9, cytochrome C and Bax protein expression in intestinal tissue in mice (p<0.01), and regulated the PI3K/Akt pathway (p<0.05, p<0.01). Importantly, the molecular docking results of AFGA also suggested a better binding ability with the above-mentioned related target proteins. result: the results showed that pretreatment with AFGA significantly ameliorated cisplatin induced oxidative stress by reducing levels of reactive oxygen species (ROS) in IEC-6 cells (p&lt;0.05, p&lt;0.01), and could effectively reduce the secretion of pro-inflammatory factors in serum and the expression level of NF-κB protein in intestinal tissues (p&lt;0.01). 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. conclusion: This study revealed AFGA as a potential multifunctional therapeutic agent with clear protective effect against cisplatin-induced intestinal injury. other: This demonstrated that AFGA can exert intestinal protective activity through PI3K/Akt and downstream caspase pathway.

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