Zhong Xiancai, Surh Young-Joon, Do Seon-Gil, Shin Eunju, Shim Kyu-Suk, Lee Chong-Kil, Na Hye-Kyung
Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
J Cancer Prev. 2019 Jun;24(2):129-138. doi: 10.15430/JCP.2019.24.2.129. Epub 2019 Jun 30.
Baicalein is a bioactive flavone that is originally extracted from the root of Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized.
The experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured.
Baicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric.
Protective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis.
黄芩素是一种生物活性黄酮，最初从黄芩的根部提取。这种植物长期以来一直作为中药用于治疗多种疾病，包括炎症性肠病。尽管已经发现黄芩素可抑制小鼠实验性结肠炎，但其分子机制仍 largely 未被认识。
通过在饮用水中添加 3% 葡聚糖硫酸钠（DSS）诱导小鼠实验性结肠炎。在给予 DSS 前后 7 天，通过灌胃给予小鼠黄芩素（10 或 25 mg/kg）。通过蛋白质免疫印迹分析检测小鼠结肠组织中 COX-2、诱导型一氧化氮合酶（iNOS）以及参与 NF-κB 信号传导的分子，如κBα 抑制剂（IκBα）、磷酸化 IκBα（pIκBα）、p65 和磷酸化 p65 的表达。通过测量转移到 IκBα 底物蛋白上的 ATP 的放射性γ-磷酸的相对量来评估 IκB 激酶β（IKKβ）的活性。还测量了 STAT3 及其靶基因细胞周期蛋白 D1 的表达和磷酸化。
黄芩素显著减轻了 DSS 诱导的小鼠结肠炎的严重程度。它抑制了 COX-2 和 iNOS 的表达。此外，黄芩素减弱了 IKKβ 的活性和磷酸化以及随后 IκBα 的降解。黄芩素抑制了 p65 的磷酸化和核转位，导致 NF-κB 的 DNA 结合活性降低。黄芩素还抑制了 STAT3 的磷酸化和细胞周期蛋白 D1 的表达。黄芩素与姜黄素（姜黄的一种成分）对 DSS 诱导的 COX-2 抑制具有协同作用。
黄芩素对 DSS 诱导的结肠炎的保护作用与抑制 NF-κB 和 STAT3 信号通路有关，这可能有助于其对结肠癌发生的癌症预防作用。
