Anemoside B4 (AB4), a triterpenoidal saponin from Pulsatilla chinensis, shows significant anti-inflammatory activity, and may be used for treating inflammatory bowel disease (IBD). Nevertheless, its application is limited due to its high molecular weight and pronounced water solubility. To discover new effective agents for treating IBD, we synthesized 28 AB4 derivatives and evaluated their cytotoxic and anti-inflammatory activities in vitro. Among them, A3–6 exhibited significantly superior anti-inflammatory activity compared to AB4. It showed a significant improvement in the symptoms of DSS-induced colitis in mice, with a notably lower oral effective dose compared to AB4. Furthermore, we discovered that A3–6 bound with pyruvate carboxylase (PC), then inhibited PC activity, reprogramming macrophage function, and alleviated colitis. These findings indicate that A3–6 is a promising therapeutic candidate for colitis, and PC may be a potential new target for treating colitis.

中文翻译：

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银莲花苷 B4 衍生物新型抗炎药的发现及其靶向丙酮酸羧化酶对结肠炎的治疗作用

Anemoside B4 (AB4) 是一种来自白头翁 ( Pulsatilla chinensis)的三萜皂苷，具有显着的抗炎活性，可用于治疗炎症性肠病 (IBD)。然而，由于其高分子量和明显的水溶性，其应用受到限制。为了发现治疗IBD的新的有效药物，我们合成了28种AB4衍生物，并在体外评估了它们的细胞毒性和抗炎活性。其中，A3-6与AB4相比表现出显着优越的抗炎活性。它对 DSS 诱导的小鼠结肠炎症状有显着改善，与 AB4 相比，口服有效剂量明显较低。此外，我们发现 A3-6 与丙酮酸羧化酶 (PC) 结合，然后抑制 PC 活性，重新编程巨噬细胞功能，并缓解结肠炎。这些发现表明A3-6是结肠炎有前途的治疗候选者，而PC可能是治疗结肠炎的潜在新靶点。