The purpose of this study is to construct a pH and redox sensitive nanoparticle to effectively deliver ginsenoside Rh₂ for the treatment of ulcerative colitis (UC). Herein, glycogen was modified by urocanic acid and α-lipoic acid (α-LA) to obtain an amphiphilic polymer (LA-UaGly). Such polymer LA-UaGly could self-assemble to form nanoparticles (Blank NPs) in water with excellent stability, which could also successfully encapsulated ginsenoside Rh₂ to form Rh₂ nanoparticles (Rh₂ NPs) with encapsulation efficiency of 74.36 ± 0.34%. DLS analysis indicated Rh₂ NPs were spherical with a particle size of 128.9 ± 0.3 nm. As expected, Rh₂ NPs exhibited typical pH and redox dual response release behaviour as well as the excellent in vivo safety. In vitro tests showed that Rh₂ NPs could effectively internalize and release Rh₂ into RAW264.7 cells, and protect cells from apoptosis (p < 0.05). More interestingly, Rh₂ NPs exhibited strong anti-inflammatory activity via significantly inhibiting the overproduction of nitric oxide (NO) and inflammatory cytokines (TNF-α, IL-1β and IL-6) (p < 0.05). In vivo experiments suggested that Rh₂ NPs significantly ameliorated the weight loss, colon length, disease activity index (DAI) score, and myeloperoxidase (MPO) activity in mice caused by dextran sulfate sodium salt (DSS) (p < 0.05). Simultaneously, pathological analysis proved that Rh₂ NPs could significantly reduce histological damage and inflammatory infiltration in mice. Rh₂ NPs could also effectively regulate the intestinal flora of mice by improving the species uniformity and abundance of the intestinal flora of mice and restoring the species diversity of the intestinal flora. In addition, both in vivo and in vitro experiments proved that Rh₂ NPs had stronger anti-inflammatory activity than Rh₂. This study provides a promising strategy for the effective treatment of UC.

本研究的目的是构建一种对 pH 和氧化还原敏感的纳米颗粒，以有效递送人参皂苷 Rh ₂以治疗溃疡性结肠炎 (UC)。在此，糖原被尿刊酸和α-硫辛酸（α-LA）修饰以获得两亲聚合物（LA-UaGly）。这种聚合物LA-UaGly可以在水中自组装形成具有优异稳定性的纳米粒子（空白纳米粒子），还可以成功包封人参皂苷Rh ₂形成Rh ₂纳米粒子（Rh ₂ NPs），包封率为74.36±0.34%。DLS 分析表明，Rh ₂ NP 呈球形，粒径为 128.9 ± 0.3 nm。正如所料，Rh ₂NPs表现出典型的pH和氧化还原双重反应释放行为以及优异的体内安全性。体外实验表明，Rh ₂ NPs可以有效地将Rh 2 内化并释放_到RAW264.7细胞中，保护细胞免于凋亡（p  < 0.05）。更有趣的是，Rh _{2 NPs通过显着抑制一氧化氮}（NO）和炎性细胞因子（TNF-α、IL-1β和IL-6）的过量产生而表现出很强的抗炎活性（ p  < 0.05）。体内实验表明，Rh ₂NPs显着改善葡聚糖硫酸钠（DSS）引起的小鼠体重减轻、结肠长度、疾病活动指数（DAI）评分和髓过氧化物酶（MPO）活性（ p  < 0.05）。同时，病理学分析证明Rh ₂ NPs可以显着降低小鼠的组织学损伤和炎症浸润。Rh ₂ NPs还可以通过改善小鼠肠道菌群的物种均一性和丰度，恢复肠道菌群的物种多样性，有效调节小鼠肠道菌群。此外，体内和体外实验均证明，Rh _{2NPs具有比Rh 2}更强的抗炎活性。本研究为有效治疗 UC 提供了一种有前景的策略。