基于脾胃虚寒型胃溃疡大鼠模型的生姜与煨姜温中散寒药效-入血成分-差异代谢物研究

Study on the Pharmacological Effects， Blood-Absorbed Components， and Differential Metabolites of Ginger and Roasted Ginger in Warming the Middle and Dispelling Cold Based on the Spleen and Stomach Deficiency-Cold Type Gastric Ulcer Rat Model

    摘要
  • 摘要:
    目的 探究生姜煨制前后对脾胃虚寒型胃溃疡大鼠的药效变化及效应物质基础。
    方法 以“苦寒泻下+过度劳倦+饥饱失常”复合吲哚美辛灌胃法复制脾胃虚寒型胃溃疡大鼠模型，比较生姜与煨姜对模型大鼠胃黏膜溃疡指数（UI）和溃疡评分，血清中表皮生长因子（EGF）、胃动素（MTL）和胃泌素（GAS）水平的影响；建立生姜成分数据库，联合UPLC-Zeno TOF-MS/MS追踪煨制前后化学成分组成、入血成分及其代谢产物变化。
    结果 生姜（2.10、1.05 g·kg-1）、煨姜（2.10、1.05 g·kg-1）均能显著降低UI与症候评分（P<0.01），提高EGF、MTL水平，降低GAS水平（P<0.05），且煨姜（2.10 g·kg-1）疗效优于等剂量生姜（P<0.05）。共推测鉴定出50个化学成分，煨制后6-姜烯酚、姜黄素、姜烯等成分相对含量上升，6-姜酚、姜酮等成分下降；大鼠血清中生姜检出24个移形成分（8个原型成分和16个代谢产物），煨姜检出47个移形成分（9个原型成分和38代谢产物），均以姜辣素类成分为主。
    结论 生姜煨制后血清中移行成分大量增加，煨姜温中散寒效应增强可能与其促进6-姜烯酚等姜辣素类成分吸收及代谢活化相关。

     

    Abstract:
    OBJECTIVE To investigate the changes in pharmacological effects and the underlying active constituents of ginger before and after being roasted in rats with spleen and stomach deficiency-cold syndrome and gastric ulcer.
    METHODS A rat model of gastric ulcer with spleen and stomach deficiency-cold syndrome was established by the “bitter cold purgation + excessive fatigue + irregular eating” combined with indomethacin gavage. The effects of ginger and roasted ginger on gastric mucosal ulcer index (UI), syndrome scores and serum levels of epidermal growth factor (EGF), motilin (MTL), and gastrin (GAS) were compared. A ginger compound database was established, and UPLC-Zeno TOF-MS/MS was used to track the changes in chemical composition, blood-absorbed components, and metabolites before and after roasting.
    RESULTS Both ginger (2.10, 1.05 g·kg-1) and roasted ginger (2.10, 1.05 g·kg-1) significantly reduced UI and syndrome scores (P<0.01), increased EGF and MTL levels, and decreased GAS levels (P<0.05). Roasted ginger (2.1 g·kg-1) was more effective than the same dose of ginger (P<0.05). A total of 50 chemical constituents were tentatively identified, with an increase in the relative content of 6-shogaol, curcumin, and zingiberene after roasting, and a decrease in 6-gingerol and gingerol. Twenty-four migration components (8 prototypes and 16 metabolites) were detected in the serum of rats treated with ginger, and 47 migration components (9 prototypes and 38 metabolites) were detected in the serum of rats treated with roasted ginger, primarily consisting of gingerol compounds.
    CONCLUSION The migration components in the serum significantly increase with roasted ginger. The enhanced middle-warming and cold-dispelling effects of roasted ginger are related to its promotion of the absorption and metabolic activation of gingerol compounds, such as 6-gingerol.

     

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