Subacute ruminal acidosis (SARA) causes an increase in endotoxin, which can induce immune and inflammatory responses in the ruminal epithelium of dairy cows. In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against SARA-induced inflammation and the underlying mechanisms are unknown. In vivo, eight ruminally cannulated Holstein cows in mid-lactation were randomly assigned to either a low-concentrate (40%) diet (CON) or a high-concentrate (60%) diet (HC) for 3 weeks to induce SARA (n = 4). Cows with SARA had greater serum concentrations of tumor necrosis factor (TNF)-α and interleukin-6, and epithelium had histological signs of damage. In vitro, immortalized bovine ruminal epithelial cells (BREC) were treated with lipopolysaccharide (LPS) to imitate the inflammatory damage caused by SARA. Our data revealed that BREC treated with 10 µg/mL LPS for 6 h successfully induce a robust inflammatory response as indicated by increased phosphorylation of IκBα and nuclear factor kappa-B (NF-κB) p65. Pre-treatment of BREC with 50 µmol/L EGCG for 6 h before LPS challenge promoted the degradation of NLR family pyrin domain containing 3 (NLRP3) inflammasome through activation of autophagy, which further repressed activation of NF-κB pathway targeting Toll-like receptor 4 (TLR4). Analyses also revealed that the ECGG upregulated tight junction (TJ) protein expression upon incubation with LPS. Subacute ruminal acidosis causes ruminal epithelium injury and systemic inflammation in dairy cows. However, the anti-inflammatory effects of EGCG help preserve the integrity of the epithelial barrier through activating autophagy when BREC are exposed to LPS. Thus, EGCG could potentially serve as an effective therapeutic agent for SARA-associated inflammation.

中文翻译：

---

表没食子儿茶素-3-没食子酸酯通过激活自噬保护牛瘤胃上皮细胞免受脂多糖诱导的炎症损伤


亚急性瘤胃酸中毒（SARA）会导致内毒素增加，从而诱发奶牛瘤胃上皮的免疫和炎症反应。在非反刍动物中，绿茶的主要生物活性成分表没食子儿茶素-3-没食子酸酯 (EGCG) 众所周知可以缓解炎症。 EGCG 是否具有针对 SARA 诱导炎症的保护作用及其潜在机制尚不清楚。在体内，八头泌乳中期的瘤胃插管荷斯坦奶牛被随机分配到低浓度（40%）饮食（CON）或高浓度（60%）饮食（HC）3周，以诱导SARA（n = 4）。患有 SARA 的奶牛血清中肿瘤坏死因子 (TNF)-α 和白细胞介素 6 的浓度较高，并且上皮有组织学损伤迹象。在体外，用脂多糖（LPS）处理永生化牛瘤胃上皮细胞（BREC）以模拟SARA引起的炎症损伤。我们的数据显示，用 10 µg/mL LPS 处理 BREC 6 小时成功诱导了强烈的炎症反应，如 IκBα 和核因子 kappa-B (NF-κB) p65 磷酸化增加所示。 LPS攻击前用50 µmol/L EGCG预处理BREC 6 h，通过激活自噬促进NLR家族pyrin结构域3（NLRP3）炎性小体的降解，从而进一步抑制针对Toll样受体的NF-κB通路的激活4（TLR4）。分析还表明，ECGG 在与 LPS 一起孵育后上调了紧密连接 (TJ) 蛋白的表达。亚急性瘤胃酸中毒会导致奶牛瘤胃上皮损伤和全身炎症。然而，当 BREC 暴露于 LPS 时，EGCG 的抗炎作用有助于通过激活自噬来保持上皮屏障的完整性。 因此，EGCG 有可能成为 SARA 相关炎症的有效治疗剂。