摘要:中药多糖是一类具有显著生物活性的药效成分,然而长期以来其体内代谢途径及机制缺乏有效研究方法,导致难以阐明多糖是否直接吸收、吸收后的代谢方式及体内分布等关键问题,严重限制了中药多糖的药物开发与临床应用。近年
中药多糖是一类具有显著生物活性的药效成分,然而长期以来其体内代谢途径及机制缺乏有效研究方法,导致难以阐明多糖是否直接吸收、吸收后的代谢方式及体内分布等关键问题,严重限制了中药多糖的药物开发与临床应用。近年来,荧光成像尤其是近红外(Near-Infrared,NIR)荧光成像技术的发展极大推动了多糖体内代谢研究技术的进步。NIR可实现非侵入式实时活体成像,具有组织穿透力强、消光系数高、生物相容性好等显著优势,为多糖体内代谢研究提供了有力的技术支撑。近期,华中科技大学同济医学院王凯平研究团队开发建立了基于荧光标记的灰树花多糖(Grifola frondose polysaccharide,GFP)代谢研究方法。该团队利用琥珀酸酐作为交联剂成功制备了NIR染料Cy5.5标记的灰树花多糖GFP- Cy5.5。体内示踪结果显示,口服给药后小鼠肝脏与肾脏呈现清晰Cy5.5荧光信号,表明肝、肾是灰树花多糖的潜在主要代谢靶器官。为研究灰树花多糖的代谢形式,该团队进一步使用DTAF标记方法制备了荧光素标记的灰树花多糖FGFP,并通过模拟消化证实FGFP可被唾液及肠液中的a-淀粉酶降解,体内实验结果则表明FGFP可进一步在远端肠中降解,代谢物分布于肝脏及肾脏并随尿液排出。上述研究为阐明灰树花多糖的代谢特征与机制奠定了基础,相关成果发表于International Journal of Biological Macromolecules杂志。
Fig. 1. The repeating unit of GFP.
Fig. 2. Characterization of fluorescently labeled GFP.
Fig. 3. Oral real-time distribution of GFP-Cy5.5 by NIR imaging.
Fig. 4. In vitro digestion of FGFP.
Fig. 5. Oral real-time gastrointestinal degradation of FGFP in vivo.
Fig. 6. Optimization of reaction conditions.
Fig. 7. Study on the mechanism of FGFP degradation.
【图片摘要】
【英文标题】
Gastrointestinal metabolism characteristics and mechanism of a polysaccharide from Grifola frondosa
【英文摘要】
Grifola frondosa polysaccharide (GFP) is mainly composed of α-1,4 glycosidic bonds and possesses multiple pharmacological activities. However, the absence of pharmacokinetic studies has limited its further development and utilization. Herein, GFP was labeled with 5-DTAF (FGFP) and cyanine 5.5 amine (GFP-Cy5.5) to investigate its gastrointestinal metabolism characteristics and mechanism. Significant distributions of the polysaccharide in the liver and kidneys were observed by near infrared imaging. To investigate the specific distribution form of the polysaccharide, in vitro digestion models were constructed and revealed that FGFP was degraded in saliva and rat small intestine extract. The metabolites were detected in the stomach and small intestine, followed by further degradation in the distal intestine in the in vivo experiment. Subsequent investigations showed that α-amylase was involved in the gastrointestinal degradation of GFP, and its metabolite finally entered the kidneys, where it was excreted directly with urine.
参考文献:
[1]《近红外荧光成像研究灰树花多糖的胃肠代谢特征与机制》
https://mp.weixin.qq.com/s/FmtPn3Uywpx1gdvUgtWHjA
[2]《Gastrointestinal metabolism characteristics and mechanism of a polysaccharide from Grifola frondosa》https://www.sciencedirect.com/science/article/abs/pii/S0141813023032531?via%3Dihu
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