Li Renshi, Chen Ce, Liu Bei, Shi Wen, Shimizu Kuniyoshi, Zhang Chaofeng
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China; Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
Phytomedicine. 2022 Jan;94:153814. doi: 10.1016/j.phymed.2021.153814. Epub 2021 Oct 18.
Bryodulcosigenin (BDG) a cucurbitane-type triterpenoid has been isolated from the roots of Bryonia dioca and possesses marked anti-inflammatory effects, although its beneficial effect against intestinal disorders remains unclear.
To explore the underlying mechanism of BDG on the dysbiosis of chronic ulcerative colitis (UC) and its associated side-effects on lung tissues.
A chronic UC model was established using 2.5% dextran sulfate sodium (DSS) in mice treated for 64 days and diagnostic assessments, western blot analysis and quantitative real time-PCR were employed to determine the protective mechanism of BDG.
Oral administration of BDG (10 mg/kg/day) significantly improved colon length, disease activity index, and alleviated colonic histopathological damage in the DSS-induced colitis mice. BDG not only reversed the TNF-α-induced degradation of tight junction proteins (occludin and ZO-1) but also suppressed the elevated apoptosis seen in intestinal epithelial cells (NCM460). In addition, BDG significantly attenuated damage in alveolar epithelial cells (MLE-12) co-cultured with NCM460 cells under inflammatory conditions. Furthermore, BDG in vivo significantly prevented the symptoms of respiratory disorders and repressed alveolar inflammation by regulating DSS-induced chronic colitis in mice.
BDG effectively inhibited the apoptosis of intestinal epithelial cells and suppressed the activation of the NLRP3 inflammasome which resulted in the restoration of the intestinal barrier. Therefore, the enhanced integrity of intestinal epithelial cells produced by BDG intervention contributed to its anti-colitis effects, indicating its great potential as an inhibitor of UC and lung injury. Therefore, restoring intestinal integrity may represent a promising strategy in the prevention of pulmonary disease.
葫芦素二烯醇苷（BDG）是一种葫芦烷型三萜类化合物，已从白泻根的根中分离出来，具有显著的抗炎作用，但其对肠道疾病的有益作用仍不清楚。
探讨BDG对慢性溃疡性结肠炎（UC）菌群失调的潜在作用机制及其对肺组织的相关副作用。
用2.5%葡聚糖硫酸钠（DSS）建立小鼠慢性UC模型，处理64天，并采用诊断评估、蛋白质免疫印迹分析和定量实时聚合酶链反应来确定BDG的保护机制。
口服BDG（10毫克/千克/天）可显著改善DSS诱导的结肠炎小鼠的结肠长度、疾病活动指数，并减轻结肠组织病理学损伤。BDG不仅逆转了肿瘤坏死因子-α（TNF-α）诱导的紧密连接蛋白（闭合蛋白和闭锁小带蛋白-1）降解，还抑制了肠上皮细胞（NCM460）中升高的细胞凋亡。此外，BDG显著减轻了在炎症条件下与NCM460细胞共培养的肺泡上皮细胞（MLE-12）的损伤。此外，体内BDG通过调节DSS诱导的小鼠慢性结肠炎，显著预防了呼吸紊乱症状并抑制了肺泡炎症。
BDG有效抑制肠上皮细胞凋亡，抑制NLRP3炎性小体的激活，从而导致肠道屏障的恢复。因此，BDG干预产生的肠上皮细胞完整性增强有助于其抗结肠炎作用，表明其作为UC和肺损伤抑制剂具有巨大潜力。因此，恢复肠道完整性可能是预防肺部疾病的一种有前景的策略。
