Application of caffeic acid or chlorogenic acid in preparing AGEs (advanced glycation end products) -induced inflammatory reaction inhibitor
阅读说明：本技术 咖啡酸或绿原酸在制备AGEs诱导的炎症反应抑制剂中的应用 (Application of caffeic acid or chlorogenic acid in preparing AGEs (advanced glycation end products) -induced inflammatory reaction inhibitor ) 是由 李冰 张振辉 李琳 张霞 苏国莹 李晓玺 徐振波 苏健裕 于 2018-08-03 设计创作，主要内容包括：本发明属于炎症反应抑制剂技术领域,公开了咖啡酸或绿原酸在制备AGEs诱导的炎症反应抑制剂中的应用。本发明技术方案主要为咖啡酸或绿原酸在制备AGEs诱导的炎症反应抑制剂中的应用。本发明中,咖啡酸或绿原酸可以直接抑制AGEs-RAGE/ROS/MAPK/NF-κB信号通路,和/或通过与AGEs相互作用,形成复合物,影响AGEs与RAGE相互作用,从而抑制AGEs-RAGE/ROS/MAPK/NF-κB信号通路,实现对炎症反应的抑制。本发明的咖啡酸与绿原酸是天然无毒副作用的物质,来源广泛,价格适宜。本发明应用抑制了AGEs诱导的炎症反应,加速了创口修复的速度,尤其是加速了糖尿病人创口修复的速度。(The invention belongs to the technical field of inflammatory reaction inhibitors, and discloses application of caffeic acid or chlorogenic acid in preparation of AGEs-induced inflammatory reaction inhibitors. The technical scheme of the invention mainly relates to the application of caffeic acid or chlorogenic acid in preparing AGEs-induced inflammatory reaction inhibitors. In the invention, caffeic acid or chlorogenic acid can directly inhibit AGEs-RAGE/ROS/MAPK/NF-kB signal pathways and/or form a compound through interaction with AGEs to influence the interaction between AGEs and RAGE, thereby inhibiting AGEs-RAGE/ROS/MAPK/NF-kB signal pathways and realizing the inhibition of inflammatory reaction. The caffeic acid and chlorogenic acid of the invention are natural substances without toxic and side effects, and have wide sources and proper price. The application of the invention inhibits AGEs-induced inflammatory reaction, accelerates the speed of wound repair, and particularly accelerates the speed of wound repair of diabetes patients.)
1. Application of caffeic acid or chlorogenic acid in preparing AGEs-induced inflammatory reaction inhibitor is provided.
2. The use of caffeic acid or chlorogenic acid as claimed in claim 1 in the preparation of AGEs-induced inflammatory response inhibitors, wherein the use is for applying AGEs-induced inflammatory response inhibitors prepared from caffeic acid or chlorogenic acid to the wound.
3. Use of caffeic acid or chlorogenic acid in the preparation of inhibitors of AGEs-induced inflammatory responses according to claim 1, characterized in that: the dose range of the caffeic acid or chlorogenic acid is 0.1-20 mu M.
Technical Field
The invention belongs to the technical field of inflammatory reaction inhibitors, and particularly relates to application of caffeic acid or chlorogenic acid in preparation of AGEs-induced inflammatory reaction inhibitors.
Background
Caffeic Acid (CA) is a natural phenolic acid in many plant foods, such as carrot, tomato, strawberry and blueberry, and belongs to phenolic acid substances in organic acids, and has a hydroxy cinnamic acid structure, chemical name of 3, 4-dihydroxy cinnamic acid, and molecular formula of C9H8O4And the molecular weight is 180.15. Caffeic acid is yellow crystal, has thermal decomposition temperature of 223-235 deg.C, is insoluble in cold water, and is soluble in hot water and organic solvent. Chlorogenic acid (chlorogenic acid) is depside composed of caffeic acid and quinic acid, iso-coffee tannic acid, chemical name 3-O-caffeoyl quinic acid, molecular formula: c16H18O9Molecular weight: 354.30. caffeic acid and chlorogenic acid are important bioactive substances, and have multiple active effects of resisting oxidation, inflammation, saccharification, cancer, tumor and HIV, and improving functions of intestine and stomach, cardiovascular and cerebrovascular system, nervous system, etc.
Advanced glycation end products (AGEs) are a class of compounds with high stability generated in the later period of Maillard reaction, and are harmful to human bodies, especially chronic inflammatory reaction caused by interaction of AGEs and RAGE. It has been found that at the wound site, after AGEs bind to RAGE, the level of reactive oxygen species in the cell increases, which in turn activates the downstream signaling pathway of the cell, causing inflammatory response, which prolongs the inflammatory response time during wound repair and impairs the wound repair function. Especially for diabetic patients, the content of AGEs in the body is higher than that of normal people, and when the diabetic patients are wounded, the AGEs with high concentration in blood are combined with skin tissue cells RAGE, so that the wounds are not easy to heal. Therefore, the inhibition of the interaction of AGEs and RAGE and the weakening of the intensity of inflammatory reaction at the wound have important significance for accelerating wound repair.
The inflammatory response is a protective immune response, which is a self-defense behavior of an innate immune system preserved in the evolution process of a human to harmful stimuli (such as pathogens, dead cells and harmful stimuli), and is strictly regulated and controlled by a host, insufficient inflammation can cause a patient to be continuously infected by the pathogens, and excessive inflammatory response can cause chronic or systemic inflammatory diseases, such as AGEs-induced continuous inflammatory response, which has adverse effects on the human body and needs to be controlled.
Disclosure of Invention
In order to overcome the disadvantages and shortcomings of the prior art, the invention provides an application of caffeic acid or chlorogenic acid in preparing AGEs-induced inflammatory reaction inhibitor.
The purpose of the invention is realized by the following scheme:
application of caffeic acid or chlorogenic acid in preparing AGEs-induced inflammatory reaction inhibitor is provided.
Furthermore, the AGEs-induced inflammatory reaction inhibitor prepared from caffeic acid or chlorogenic acid is applied to wound.
Further, the dose range of the caffeic acid or the chlorogenic acid is 0.1-20 mu M.
In the application of the invention, caffeic acid or chlorogenic acid realizes the effect of inhibiting inflammatory reaction by inhibiting the interaction of AGEs and RAGE in the wound repair process.
In the invention, caffeic acid or chlorogenic acid inhibits inflammatory reaction by inhibiting AGEs-RAGE/ROS/MAPK/NF-kB signal channels. Specifically, caffeic acid or chlorogenic acid can directly inhibit AGEs-RAGE/ROS/MAPK/NF-kB signal pathways, and/or interact with AGEs to form a compound to influence the interaction of AGEs and RAGE, so that AGEs-RAGE/ROS/MAPK/NF-kB signal pathways are inhibited, and the inhibition of inflammatory reaction is realized.
After AGEs are combined with RAGE, a large amount of ROS can be generated in cells and an intracellular signal path is activated, so that the expression quantity of related kinases is increased, such as MAPK, NF-kB and the like, and the cells are induced to generate inflammatory response.
The research of the invention finds that caffeic acid or chlorogenic acid has no obvious cytotoxicity on Human Umbilical Vein Endothelial Cells (HUVEC) within the concentration range of 0.1-20 mu M, can obviously inhibit the generation of ROS (glycated bovine serum albumin-BSA, a protein-bound AGEs), and has stronger inhibition effect along with the increase of the treatment concentration of the drug.
The inhibitor inhibits the interaction of AGEs and RAGE to inhibit inflammatory reaction by inhibiting AGEs-RAGE/ROS/MAPK/NF-kB signal channels generated by the interaction of AGEs and RAGE and/or forming a compound by the interaction of AGEs and AGEs in the process of wound repair.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1. the inhibitor caffeic acid and chlorogenic acid related by the invention are natural substances without toxic and side effects, and have wide sources and proper price.
2. The invention expands the application of caffeic acid and chlorogenic acid in the field of wound repair, inhibits AGEs-induced inflammatory reaction, and accelerates the speed of wound repair, in particular the speed of wound repair of diabetes patients.
Drawings
FIG. 1 is a graph showing the effect of different concentrations of caffeic acid on the expression levels of ICAM-1, VCAm-1 and MCP-1mRNA in HUVEC cells induced by AGEs-BSA.
FIG. 2 is a graph showing the effect of different concentrations of caffeic acid on the amount of expression of TNF- α and IL-1 β proteins in HUVEC cells induced by AGEs-BSA.
FIG. 3 is a graph showing the effect of different concentrations of caffeic acid on the amount of RAGE mRNA expression in HUVEC cells induced by AGEs-BSA.
FIG. 4 is a graph showing the effect of different concentrations of caffeic acid on the amount of RAGE protein expression in HUVEC cells induced by AGEs-BSA.
FIG. 5 is a graph showing the effect of different concentrations of caffeic acid on the amount of p38MAPK and NF-. kappa.B protein expression in HUVEC cells induced by AGEs-BSA.
FIG. 6 is a graph showing the effect of different concentrations of chlorogenic acid on the expression levels of ICAM-1, VCAm-1 and MCP-1mRNA in HUVEC cells induced by AGEs-BSA.
FIG. 7 is a graph showing the effect of different concentrations of chlorogenic acid on the amount of expression of TNF- α and IL-1 β proteins in HUVEC cells induced by AGEs-BSA.
FIG. 8 is a graph of the effect of different concentrations of chlorogenic acid on the amount of RAGE mRNA expression in HUVEC cells induced by AGEs-BSA.
FIG. 9 is a graph of the effect of different concentrations of chlorogenic acid on the amount of RAGE protein expression in HUVEC cells induced by AGEs-BSA.
FIG. 10 is a graph showing the effect of different concentrations of chlorogenic acid on the amount of p38MAPK and NF-. kappa.B protein expression in HUVEC cells induced by AGEs-BSA.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.
The materials referred to in the following examples are commercially available.