Abstract：
Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by self-assembly of epigallocatechin gallate (EGCG) and FeCl3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo, NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.
摘要：
炎症性肠病（IBD）的病因与氧化应激和炎性小体激活密切相关。天然抗氧化剂川陈皮素(NOB)在减轻肠道损伤方面具有优异的抗炎特性。然而,水溶性不足和生物利用度低限制了其对IBD的口服干预。在这里，我们构建了一种高效的负载NOB的酵母微胶囊(YM，NEFY）在低口服剂量的NOB（20mg/kg）下对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）表现出明显的治疗效果。我们利用表没食子儿茶素没食子酸酯（EGCG）和FeCl3自组装形成的金属多酚网络（MPN）作为中间载体，将NOB的包封率（EE）提高了4.2倍。这些微胶囊有效缓解了脂多糖（LPS）诱导的RAW264.7巨噬细胞的炎症反应和氧化应激。在体内,具有生物相容性的NEFY通过控制胃肠道释放和巨噬细胞靶向使NOB的肠道富集成为可能。此外,NEFY能抑制NLRP3炎性体,平衡巨噬细胞极化,这有利于完整的肠粘膜屏障和结肠炎的恢复。基于YM的口服靶向给药平台,这项工作提出了一种开发和利用天然黄酮NOB干预肠道炎症相关疾病的新策略。
