Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanis...Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanism via gut microbiota.Methods:The pharmacodynamics of Gegen Qinlian decoction(GQD)were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis(UC).Ultra-performance liquid chromatographyquadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC.To analyze the structure and function of characteristic genera of GQD and its active components,16S rRNA sequencing was performed.Results:We identified 67 prototypic and 14 metabolic components of GQD in the UC colon.The primary prototype components are flavonoids and alkaloids,including puerarin(PUE),baicalin(BAI),and berberine(BER).The metabolism was predominantly sulfonation.Efficacy verification showed that the main active components,puerarin,baicalin,and berberine,had good therapeutic effects on UC.The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota.The abundance of gut microbiota involved in the metabolism of the prototype componentswas influenced by the corresponding components.The function prediction results showed that PUE was the most comparable to GQD,with 24 consistent pathways.BAI and BER showed comparable gut microbiota regulation pathways.Characteristic pathways of BER include glucometabolic processes.Conclusion:This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components.This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC,as well as changes in the structure and function of the gut microbiota,clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.展开更多
Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane(CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications th...Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane(CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol(PEG) was used to modifying magnetic graphene oxide(MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine(TCM). With this strategy, the constructed PEGylated MGO(PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of He La cell membrane(HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity(116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin,and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surfaceengineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.展开更多
基金supported by Fundamental Research Funds for the Central Universities(2022-ZXFZJJ-028).
文摘Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanism via gut microbiota.Methods:The pharmacodynamics of Gegen Qinlian decoction(GQD)were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis(UC).Ultra-performance liquid chromatographyquadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC.To analyze the structure and function of characteristic genera of GQD and its active components,16S rRNA sequencing was performed.Results:We identified 67 prototypic and 14 metabolic components of GQD in the UC colon.The primary prototype components are flavonoids and alkaloids,including puerarin(PUE),baicalin(BAI),and berberine(BER).The metabolism was predominantly sulfonation.Efficacy verification showed that the main active components,puerarin,baicalin,and berberine,had good therapeutic effects on UC.The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota.The abundance of gut microbiota involved in the metabolism of the prototype componentswas influenced by the corresponding components.The function prediction results showed that PUE was the most comparable to GQD,with 24 consistent pathways.BAI and BER showed comparable gut microbiota regulation pathways.Characteristic pathways of BER include glucometabolic processes.Conclusion:This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components.This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC,as well as changes in the structure and function of the gut microbiota,clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.
基金National Natural Science Foundation of China(Nos.82073807 and 81973277)the WorldClass Universities(Disciplines)and the Characteristic Development Guidance Funds for the Central Universities(No.PY3A012,China)for financial support。
文摘Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane(CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol(PEG) was used to modifying magnetic graphene oxide(MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine(TCM). With this strategy, the constructed PEGylated MGO(PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of He La cell membrane(HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity(116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin,and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surfaceengineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.
