目的 针对药食同源复方五汁饮液体制剂储存期易发生的非酶褐变难题，系统解析其褐变机制，并评价抗褐变工艺制备的五汁饮对酒精性胃损伤的保护作用。方法 采用非靶向代谢组学超高效液相色谱-质谱联用（ultra-performance liquid chromatography-mass spectrometry，UPLC-MS）结合Spe-Pak微柱分离技术，分析五汁饮褐变前后差异代谢物及褐变中间体；以颜色、褐变度及营养成分变化表征褐变程度；建立无水乙醇诱导小鼠急性胃损伤模型，评价抗褐变工艺制备的五汁饮胃保护功能。结果 褐变导致总糖、总多酚及总氨基酸含量显著下降（P＜0.05）。筛选出19种关键差异化合物，其中果糖、蔗糖、缬氨酸、异亮氨酸、酪氨酸及对香豆酸为主要驱动因子；鉴定出核心褐变中间体为2-羟基-3-甲基-2-环戊烯-1-酮，证实褐变由美拉德反应、酸催化糖降解及酚类氧化交联共同驱动；抗褐变工艺制备的五汁饮高剂量（43.72 g/kg）可显著降低小鼠胃溃疡指数（抑制率72.42%），减轻胃黏膜病理损伤，其机制与抑制核因子-κB（nuclear factor-κB，NF-κB）通路，降低炎症因子［白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、IL-6］，调节氧化应激［升高超氧化物歧化酶（superoxide dismutase，SOD）/丙二醛比值］及保护黏膜屏障［（调节NO、前列腺素E₂（prostaglandin E₂，PGE₂）、三叶因子2（trefoil factor 2，TFF2）］相关。结论 果糖、蔗糖、缬氨酸、异亮氨酸、酪氨酸及对香豆酸是五汁饮褐变的关键驱动因子；美拉德反应、酸催化糖降解及酚类氧化交联是其主要褐变途径；抗褐变工艺制备的五汁饮对酒精性胃损伤具有显著保护功能。

Objective Given that the liquid formulation of the medicine-food homology formula Wuzhiyin is susceptible to non-enzymatic browning during storage, this study systematically investigates the underlying browning mechanism and evaluates the gastroprotective effect of Wuzhiyin prepared using an anti-browning processing technology against alcoholic gastric injury. Methods The differential metabolites and browning intermediates before and after browning of Wuzhiyin were analyzed by non-targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and Spe-Pak microcolumn separation technology. The degree of browning was characterized by color changes, browning degree, and alterations in nutritional components. An anhydrous ethanol-induced acute gastric injury mouse model was established to evaluate the gastroprotective function of anti-browning prepared Wuzhiyin. Results Total sugars, total polyphenols, and total amino acids were significantly decreased by browning (P < 0.05). Nineteen key differential compounds were screened, among which fructose, sucrose, valine, isoleucine, tyrosine, and p-coumaric acid were identified as major driving factors. 2-Hydroxy-3-methyl-2-cyclopenten-1-one was identified as the core browning intermediate, and the browning mechanism was elucidated as a synergistic process involving the Maillard reaction, acid-promoted sugar degradation, and oxidative cross-linking of phenolic compounds. High-dose anti-browning prepared Wuzhiyin (43.72 g/kg) significantly reduced the gastric ulcer index (inhibition rate 72.42%) and alleviated pathological damage to the gastric mucosa. The underlying mechanisms include inhibiting nuclear factor-κB (NF-κB) pathway, reducing inflammatory cytokines [interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6], regulating oxidative stress [elevation of superoxide dismutase (SOD)/malondialdehyde ratio], and protecting mucosal barrier [modulation of NO, prostaglandin E₂ (PGE₂), trefoil factor 2 (TFF2)]. Conclusion Fructose, sucrose, valine, isoleucine, tyrosine, and p-coumaric acid are the key drivers of browning in Wuzhiyin; the Maillard reaction, acid-catalyzed sugar degradation, and phenolic oxidative cross-linking constitute the major browning pathways; and Wuzhiyin prepared via the anti-browning processing technology exhibits a significant gastroprotective effect against alcoholic gastric injury.

R283.6

国家自然科学基金青年基金资助项目（81904088）；国家中医药管理局创新团队和人才培养计划（ZYYCXTD-D-202209）；中国博士后科学基金第76批面上资助项目（2024MD763926）；四川省科技厅青年基金项目（2025ZNSFSC1804）；博士后科研项目特别资助（TB2025092）；成都中医药大学2024-2025年度大学生科研实践创新项目（ky-2025069）