Department of Pharmacology of Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Department of Spine Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Phytother Res. 2018 Sep;32(9):1770-1783. doi: 10.1002/ptr.6108. Epub 2018 Jun 7.
Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proven effective in preventing tumor progression in previous studies. Ulcerative colitis (UC) is a common inflammatory bowel disease that affects millions of people worldwide, but no effective and safe drugs are available. In this study, we aimed to study how did casticin affect UC by evaluating its effects on dextran sulfate sodium (DSS)-induced colitis in mice. Our data suggested that casticin attenuated body weight loss, colon length shortening, and pathological damage in the colon of DSS-treated mice. Casticin decreased reactive oxygen species level and chemocytokines (IL-1β, IL-6, TNF-α) productions in colon tissue. The decreased reactive oxygen species level and suppressed proinflammatory cytokines productions were also confirmed in casticin-treated LPS-stimulated RAW264.7 cells and hydrogen peroxide-treated CACO-2 cells in vitro. Mechanistically, casticin treatment prevented the profound activation of AKT signaling caused by DSS administration. And casticin inhibited the productions of proinflammatory chemocytokines through downregulating AKT/NF-κB pathway in macrophages. Meanwhile, data revealed that casticin increased expressions of endogenous antioxidants peroxiredoxin 3 and MnSOD were through activation in FOXO3α signaling by downregulating AKT signaling in colon epithelium cells. Our findings demonstrated that casticin alleviated DSS-induced UC by increasing the antioxidant enzyme peroxiredoxin 3 and MnSOD expressions, and decreasing the production of proinflammatory chemocytokines through inhibition of AKT signaling.
金雀异黄素，一种从中药桑白皮中分离得到的化合物，已被证明在先前的研究中能有效预防肿瘤进展。溃疡性结肠炎（UC）是一种常见的炎症性肠病，影响着全球数以百万计的人，但目前尚无有效和安全的药物。在这项研究中，我们旨在通过评估金雀异黄素对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的影响，来研究金雀异黄素如何影响 UC。我们的数据表明，金雀异黄素减轻了 DSS 处理小鼠的体重减轻、结肠缩短和结肠组织病理学损伤。金雀异黄素降低了结肠组织中的活性氧水平和化学趋化因子（IL-1β、IL-6、TNF-α）的产生。在体外，金雀异黄素处理的 LPS 刺激的 RAW264.7 细胞和过氧化氢处理的 CACO-2 细胞中，也证实了活性氧水平的降低和促炎细胞因子产生的抑制。在机制上，金雀异黄素治疗可防止 DSS 给药引起的 AKT 信号的深度激活。并且，金雀异黄素通过抑制巨噬细胞中 AKT/NF-κB 通路，下调促炎细胞因子的产生，从而抑制炎症细胞因子的产生。同时，数据表明，金雀异黄素通过下调 AKT 信号，增加了内源性抗氧化酶过氧化物酶 3 和 MnSOD 的表达，从而激活 FOXO3α 信号，从而增加了结肠上皮细胞中的表达。我们的研究结果表明，金雀异黄素通过增加抗氧化酶过氧化物酶 3 和 MnSOD 的表达，以及通过抑制 AKT 信号减少促炎细胞因子的产生，从而缓解 DSS 诱导的 UC。
