Dept. of Infectious Diseases, Renmin Hospital of Wuhan Univ., Wuhan 430060, Hubei Province, PR China; Hubei Key Laboratory of Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, PR China.
Dept. of Infectious Diseases, Renmin Hospital of Wuhan Univ., Wuhan 430060, Hubei Province, PR China; Hubei Key Laboratory of Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, PR China.
Int Immunopharmacol. 2018 Nov;64:256-263. doi: 10.1016/j.intimp.2018.09.009. Epub 2018 Sep 12.
Inflammation, oxidative stress and epithelial barrier dysfunction have been implicated in inflammatory bowel disease (IBD) pathology. The targeted inhibition of these features may represent a promising therapeutic strategy for IBD. Polydatin is an effective natural antioxidant that possesses strong antioxidant and anti-apoptotic properties. Thus, we studied the protective effects of polydatin treatments on a mouse model of experimental colitis.
Acute colitis was experimentally induced by adding 3% dextran sulfate sodium (DSS) to the drinking water provided to mice for 7 days and by administering different doses of polydatin (15, 30, or 45 mg/kg) during the same period. Mice were also treated with the Sonic hedgehog (Shh) pathway inhibitor cyclopamine to estimate the efficacy of polydatin and Shh inhibitors on colitis. The disease activity index (DAI), colon length, histology, levels of oxidative and apoptotic mediators and levels of Shh pathway components were evaluated.
The polydatin treatment significantly attenuated the DAI, colon shortening and histological damage. In addition, polydatin administration effectively decreased malondialdehyde (MDA) levels and increased the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Polydatin also inhibited apoptosis in mice with colitis by downregulating the expression of the pro-apoptotic proteins Bax, caspase 3 and cleaved caspase 3 and increasing the expression of the anti-apoptotic protein Bcl-2. Furthermore, polydatin modulated Shh signaling pathway activation. After polydatin treatment, the main components of the Shh pathway, including Shh, Patched (Ptc), Smoothened (Smo), and glioblastoma-1 (Gli1), were upregulated at the mRNA and protein levels. Blockade of the Shh pathway using cyclopamine abolished the effects of polydatin on mice with colitis.
Based on these observations, polydatin may suppress experimental colitis at least partially by regulating the Shh signaling pathway.
炎症、氧化应激和上皮屏障功能障碍与炎症性肠病（IBD）的病理有关。靶向抑制这些特征可能代表一种有前途的 IBD 治疗策略。虎杖苷是一种有效的天然抗氧化剂，具有很强的抗氧化和抗凋亡特性。因此，我们研究了虎杖苷治疗对实验性结肠炎小鼠模型的保护作用。
通过在饮用水中添加 3%葡聚糖硫酸钠（DSS），将小鼠诱导为急性结肠炎，持续 7 天，并在同一时期给予不同剂量的虎杖苷（15、30 或 45mg/kg）。还使用 Sonic hedgehog（Shh）途径抑制剂环巴胺治疗小鼠，以评估虎杖苷和 Shh 抑制剂对结肠炎的疗效。评估疾病活动指数（DAI）、结肠长度、组织学、氧化和凋亡介质水平以及 Shh 途径成分水平。
虎杖苷治疗显著减轻了 DAI、结肠缩短和组织学损伤。此外，虎杖苷给药还能有效降低丙二醛（MDA）水平，增加抗氧化酶超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性。虎杖苷还通过下调促凋亡蛋白 Bax、caspase 3 和 cleaved caspase 3 的表达，增加抗凋亡蛋白 Bcl-2 的表达，抑制结肠炎小鼠的凋亡。此外，虎杖苷还调节了 Shh 信号通路的激活。虎杖苷治疗后，Shh 通路的主要成分，包括 Shh、Patched（Ptc）、Smoothened（Smo）和 glioblastoma-1（Gli1），在 mRNA 和蛋白水平上均上调。使用环巴胺阻断 Shh 途径可消除虎杖苷对结肠炎小鼠的作用。
基于这些观察结果，虎杖苷可能至少部分通过调节 Shh 信号通路来抑制实验性结肠炎。
