An old herbal medicine with a potentially new therapeutic application in inflammatory bowel disease.
An old herbal medicine with a potentially new therapeutic application in inflammatory bowel disease.
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发表时间：
2011
影响因子：
0.1
通讯作者：
Richard Li;P. Alex;M. Ye;Ting Zhang;Ling Liu;Xuhang Li
中科院分区：
文献类型：
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作者：
Richard Li;P. Alex;M. Ye;Ting Zhang;Ling Liu;Xuhang Li
炎症性肠病(IBD)是一种慢性、常见的致残性肠炎性疾病。IBD治疗的新进展主要集中在生物治疗上；然而，它们都很昂贵，而且与显著的副作用有关。在这里，我们提供了第一个临床前证据表明，云南白药(YNBY)，一种著名的中草药，经常用于治疗出血和伤口，可以有效地缓解实验性结肠炎。口服YNBY可显著降低DSS和TNBS诱导的实验性结肠炎的疾病活动性。机理研究表明，YNBY的有效性不是由于抗菌功能，因为YNBY对大肠杆菌的生长没有影响。相反，它表现出抗炎或免疫抑制的作用：在DSS结肠炎模型中，养脾益气饮治疗降低了结肠粘膜中几种促炎细胞因子的水平，包括肿瘤坏死因子α、IL-12p40和IL-17。在小鼠血清中也观察到了类似的细胞因子变化，这表明全身变化总体上反映了受影响的结肠的变化。在结肠炎模型中，除干扰素γ外，IL-12p40和IL-17的表达也显著下调。YNBY抗炎作用的另一个潜在机制是选择性抑制促炎免疫细胞：YNBY有效地抑制多种T和B淋巴细胞的生长，包括Molt-4、Jurkat和EBV转化的B淋巴细胞，比IBD治疗中最常用的两种一线药物6-甲酚嘌呤(6-MP)和5-氨基水杨酸(5-ASA)更有效。与之形成鲜明对比的是，YNBY对结肠上皮细胞(Caco-2细胞)没有细胞毒性，即使在比淋巴细胞模型中使用的浓度高10倍的情况下也是如此；相反，YNBY促进了细胞扩散和伤口愈合。这些结果有力地表明，养阴养阴不仅通过抑制淋巴细胞生长和促炎细胞因子的表达而具有有效的抗炎作用，而且还可以促进肠上皮损伤的愈合和修复。因此，养阴益气饮作为治疗IBD的一种替代中药疗法显示出很强的潜力。
Inflammatory Bowel Disease (IBD) is a chronic and frequently disabling inflammatory disorder of the intestine. New developments in IBD therapy are primarily focused on biologic treatments; however, they are both expensive and associated with significant side effects. Here, we provide the first preclinical evidence that YunNan BaiYao (YNBY), a well-known traditional Chinese herbal remedy frequently used for treating hemorrhages and wounds, can effectively alleviate experimental colitis. Oral administration of YNBY in drinking water significantly reduced the disease activities of both DSS- and TNBS-induced experimental colitis. Mechanistic studies revealed that the effectiveness of YNBY was not due to an anti-bacterial function since YNBY had no effect on E. coli growth. Rather, it exhibited an anti-inflammatory or immunosuppressive function: In the DSS colitis model, YNBY treatment decreased the levels of several pro-inflammatory cytokines in colonic mucosa, including TNFα, IL-12p40, and IL-17. Similar cytokine changes were also observed in mouse serum, suggesting that systemic changes in general reflect the changes in the affected colon. Significant down-regulation of IL-12p40 and IL-17, in addition to IFNγ, was also seen in TNBS-colitis model. Another potential mechanism for the anti-inflammatory effects of YNBY involves the selective suppression of pro-inflammatory immune cells: YNBY effectively suppressed the growth of multiple T- and B-lymphocytes, including Molt-4, Jurkat, and EBV-transformed human B-lymphocytes, more potently than 6-mecaptopurine (6-MP) and 5-aminosalicylic acid (5-ASA), two of the most commonly used first-line drugs in IBD therapy. In sharp contrast, YNBY exhibited no cytotoxicity to colonic epithelial cells (Caco-2 cells), even at the concentration 10-fold higher than that used in the lymphocyte model; and instead promoted cell spreading and wound healing. These results strongly suggest that YNBY not only has effective anti-inflammatory properties through suppressing lymphocyte growth and pro-inflammatory cytokine expression, but also can promote intestinal epithelial wound-healing and repair. Therefore, YNBY demonstrates strong potential as an alternative herbal therapy for IBD.