State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Biochem Pharmacol. 2015 Mar 15;94(2):142-54. doi: 10.1016/j.bcp.2015.02.002. Epub 2015 Feb 10.
Previous studies have demonstrated that wogonoside, the glucuronide metabolite of wogonin, has anti-inflammatory, anti-angiogenic and anticancer effects. However, the anti-inflammatory mechanism of wogonoside has not been fully elucidated. Recently, NLRP3 inflammasome has been reported to be correlated with inflammatory bowel disease for its ability to induce IL-1β release. Nevertheless, there are few drug candidates targeting NLRP3 inflammasome for this disease. In this study, we investigated the anti-inflammatory effect of wogonoside in dextran sulfate sodium (DSS)-induced murine colitis and further revealed the underlying mechanisms by targeting NF-κB and NLRP3 inflammasome. Wogonoside treatment dose-dependently attenuated DSS-induced body weight loss and colon length shortening. Moreover, wogonoside prevented DSS-induced colonic pathological damage, remarkably inhibited inflammatory cells infiltration and significantly decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities. The production of pro-inflammatory mediators in serum and colon was also significantly reduced by wogonoside. The underlying mechanisms for the protective effect of wogonoside in DSS-induced colitis may be attributed to its inhibition on NF-κB and NLRP3 inflammasome activation in colons. Furthermore, wogonoside markedly decreased production of IL-1β, TNF-α and IL-6 and suppressed mRNA expression of pro-IL-1β and NLRP3 in phorbol myristate acetate (PMA)-differentiated monocytic THP-1 cells via inhibiting the activation of NF-κB and NLRP3 inflammasome. In conclusion, our study demonstrated that wogonoside may exert its anti-inflammatory effect via dual inhibition of NF-κB and NLRP3 inflammasome, suggesting that wogonoside might be a potential effective drug for inflammatory bowel diseases.
先前的研究表明，黄苓苷是黄苓素的葡萄糖醛酸代谢物，具有抗炎、抗血管生成和抗癌作用。然而，黄苓苷的抗炎机制尚未完全阐明。最近，NLRP3 炎性体因其能够诱导 IL-1β 释放而被报道与炎症性肠病相关。然而，针对这种疾病，针对 NLRP3 炎性体的药物候选物很少。在这项研究中，我们研究了黄苓苷在葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎中的抗炎作用，并通过靶向 NF-κB 和 NLRP3 炎性体进一步揭示了其潜在机制。黄苓苷治疗剂量依赖性地减轻了 DSS 诱导的体重减轻和结肠缩短。此外，黄苓苷可预防 DSS 诱导的结肠病理损伤，显著抑制炎症细胞浸润，并显著降低髓过氧化物酶（MPO）和诱导型一氧化氮合酶（iNOS）活性。黄苓苷还显著降低了血清和结肠中促炎介质的产生。黄苓苷在 DSS 诱导的结肠炎中的保护作用的潜在机制可能归因于其对结肠中 NF-κB 和 NLRP3 炎性体激活的抑制作用。此外，黄苓苷通过抑制 NF-κB 和 NLRP3 炎性体的激活，显著降低 PMA 分化的单核细胞 THP-1 细胞中 IL-1β、TNF-α 和 IL-6 的产生，并抑制 pro-IL-1β 和 NLRP3 的 mRNA 表达。总之，我们的研究表明，黄苓苷可能通过双重抑制 NF-κB 和 NLRP3 炎性体发挥其抗炎作用，提示黄苓苷可能是一种治疗炎症性肠病的有效药物。
