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引用次数: 0
摘要
饮食干预对酒精性肝损伤的临床治疗至关重要。作为发酵茶的主要生物活性成分,茶黄素-3,3'-二二酸酯(TF3)具有强大的抗氧化和抗炎能力,但其通过肠-肝轴对酒精性肝损伤的保护机制尚待系统阐明。本研究评价了高纯度TF3 (2.5/5/10 mg/kg,灌胃12周)对C57BL/6J小鼠酒精性肝损伤的保护作用及其机制。TF3显著降低了酒精喂养小鼠的血脂,减轻了肝脏脂肪变性,抑制了氧化应激和促炎细胞因子的产生。在机制上,TF3通过上调结肠和回肠紧密连接蛋白,增加乳酸菌和双歧杆菌等有益菌群,调节短链脂肪酸(SCFAs)和色氨酸等微生物代谢物,增强肠道屏障的完整性。这些变化降低了循环脂多糖(LPS),抑制了肝脏toll样受体4 (TLR4)/核因子κ b (NF-κB)通路的激活,最终改善了肝脏炎症,同时增强了氧化应激调节。本研究揭示了TF3预防酒精性肝损伤的新机制,为其在饮食中的应用提供了理论基础。
Theaflavin-3,3´-Digallate Prevents Alcoholic Liver Injury by Suppressing Hepatic TLR4/NF-κB Signaling and Modulating the Gut-Liver Axis in Mice.
Dietary intervention is crucial for the clinical management of alcoholic liver injury. As the primary bioactive component in fermented tea, theaflavin-3,3'-digallate (TF3) possesses potent antioxidative and anti-inflammatory capacities, but its protective mechanisms against alcoholic liver injury via the gut-liver axis require systematic elucidation. This study evaluated the protective effects and underlying mechanisms of high-purity TF3 (2.5/5/10 mg/kg, 12-week oral gavage) against alcoholic liver injury in C57BL/6J mice. TF3 administration significantly reduced serum lipids, attenuated hepatic steatosis, and suppressed oxidative stress and pro-inflammatory cytokine production in alcohol-fed mice. Mechanistically, TF3 enhanced intestinal barrier integrity by upregulating tight junction proteins in the colon and ileum, increased beneficial microbiota like Lactobacillus and Bifidobacterium, and modulated microbial metabolites including short-chain fatty acids (SCFAs) and tryptophan. These changes reduced circulating lipopolysaccharide (LPS), suppressed hepatic toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activation, and ultimately ameliorated hepatic inflammation while enhancing oxidative stress regulation. This work reveals novel mechanisms of TF3 in preventing alcoholic liver injury, providing a theoretical foundation for dietary applications.
期刊介绍:
Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology.
Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.