Palmatine (PAL) is an isoquinoline alkaloid derived from Fibraureae caulis Pierre that has been used to relieve inflammatory diseases like ulcerative colitis (UC). The metabolites of PAL were believed to contribute significantly to its outstanding biological activities. 8-Oxypalmatine (OPAL), a liver-mediated oxidative metabolite of PAL, has been firstly identified in the present work. We aimed to comparatively investigate the potential effect and mechanism of OPAL and PAL on dextran sodium sulfate (DSS)-induced colitis in Balb/c mice. Results indicated that OPAL and PAL effectively mitigated clinical manifestations, DAI scores and pathological damage compared with the model group. Moreover, treatment with OPAL and PAL effectively mitigated oxidative stress markers and inflammatory mediators in colon. Additionally, OPAL and PAL significantly activated the Nrf2 pathway, while substantially suppressed the activation of NLRP3 inflammasome. Furthermore, OPAL showed superior anti-colitis effect to PAL, which was similar to the positive drug mesalazine with much smaller dosage. These findings suggested that OPAL exerted appreciable protective effect on DSS-induced colitis, at least in part, via activating Nrf2 pathway and inhibiting NLRP3 inflammasome. OPAL might have the potential to be further developed into a promising candidate for the treatment of UC.

巴马汀 (PAL) 是一种异喹啉生物碱，来源于Fibraureae caulis皮埃尔已被用于缓解溃疡性结肠炎 (UC) 等炎症性疾病。PAL 的代谢物被认为对其杰出的生物活性有重大贡献。8-Oxypalmatine (OPAL) 是一种肝脏介导的 PAL 氧化代谢物，已在本工作中首次被发现。我们旨在比较研究OPAL和PAL对葡聚糖硫酸钠（DSS）诱导的Balb/c小鼠结肠炎的潜在作用和机制。结果表明，与模型组相比，OPAL和PAL可有效减轻临床表现、DAI评分和病理损伤。此外，用 OPAL 和 PAL 治疗有效地减轻了结肠中的氧化应激标志物和炎症介质。此外，OPAL 和 PAL 显着激活了 Nrf2 通路，同时大大抑制了 NLRP3 炎性体的激活。此外，OPAL 显示出优于 PAL 的抗结肠炎作用，这与阳性药物美沙拉嗪相似，但剂量要小得多。这些发现表明，OPAL 至少部分通过激活 Nrf2 通路和抑制 NLRP3 炎性体对 DSS 诱导的结肠炎发挥了明显的保护作用。OPAL 可能有潜力进一步发展成为治疗 UC 的有希望的候选者。