华南农业大学学报2025，Vol.46Issue(3)：301-310,10.DOI:10.7671/j.issn.1001-411X.202405012
大黄酸衍生物的合成及抗感染活性评价
Synthesis and anti-inflammatory activity evaluation of rhein derivatives
摘要
Abstract
[Objective]To conduct structural modification of rhein by using hydroxydecanoic acid and decanol as modifiers,increase lipid solubility of rhein,reduce toxic effects,and improve anti-inflammatory and antioxidant effects for potential clinical application.[Method]Firstly,based on the structure-activity relationship of rhein,the carboxyl group in rhein was selected for esterification with ten-carbon hydroxydecanoic acid and decanol to synthesize four rhein derivatives including rhubarb-5-hydroxydecanol(R-5HD),rhubarb-hydroxydecanol(R-DA),rhubarb-10-hydroxydecanoic acid(R-10HA)and rhubarb-10-hydroxy-2-denoic acid(R-10HDA).The chemical structural characteristic of rhein derivatives were investigated by 1H nuclear magnetic resonance(1H NMR)and Fourier transform infrared spectroscopy(FTIR).Secondly,the CCK-8 kit was used to determine the effects of rhein derivatives on survival rates of mouse mononuclear macrophage cells RAW 264.7.The most suitable concentration ranges of rhein and its derivatives were determined according to the survival rates of cells.Finally,to further verify the anti-inflammatory activity of rhein derivatives,a lipopolysaccharide(LPS)-induced RAW 264.7 cell model was constructed,and the reactive oxygen species(ROS)level,nitric oxide(NO)release amount,as well as tumour necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)expressions were determined.The antioxidant activity of rhein derivatives were analyzed by the ROS fluorescent probe 2,7-dichlorofluorescin diacetate(DCFH-DA).[Result]Four rhein derivatives were prepared successfully and proved by 1H NMR and FTIR.The in vitro anti-inflammatory model validation showed that the cytotoxicity of rhein after modification was significantly reduced;Four rhein derivatives significantly increased the cell viability of RAW 264.7 compared with rhein.The rhein derivatives had better anti-inflammatory and antioxidant activity in the LPS-treated RAW 264.7 cell model.All four rhein derivatives significantly reduced NO release,as well as the expressions of TNF-α,IL-6 and IL-β.All four rhein derivatives significantly inhibited ROS production compared to rhein.[Conclusion]This study focuses on the structural modification of rhein by hydroxydecanoic acid and decanol.In vitro experiment confirmes that R-DA has stronger anti-inflammatory and antioxidant activities,which provides a theoretical basis for the subsequent research and development of rhein derivatives.关键词
大黄酸/羟基癸酸/癸醇/大黄酸衍生物/抗感染/抗氧化Key words
Rhein/Hydroxydecanoic acid/Decanol/Rhein derivative/Anti-inflammatory/Antioxidant分类
农业科技引用本文复制引用
李志鹏,谭露露,邓尧,任昊,廖晓萍,孙坚,韩璐..大黄酸衍生物的合成及抗感染活性评价[J].华南农业大学学报,2025,46(3):301-310,10.基金项目
国家重点研发计划(2023YFD1800100) （2023YFD1800100）
