J Adv Res|王胜鹏团队揭示小檗碱/单宁酸靶向治疗溃疡性结肠炎的新方向

2022年8月4日 0条评论 387次阅读 0人点赞

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《J Adv Res|王胜鹏团队揭示小檗碱/单宁酸靶向治疗溃疡性结肠炎的新方向》

UC是一种慢性复发性特发性疾病，其特征是结肠上皮屏障受损和炎症稳态破坏，目前，UC尚无根治性疗法。有研究指出，来自CM大黄和黄连的TA和BBR两种活性成分对结肠炎具有良好的治疗作用。2021年11月29日，澳门大学中医药科学研究所中医药质量研究国家重点实验室王胜鹏团队在Journal of Advanced Research上发表了题为“Targeted delivery of Chinese herb pair-based berberine/tannin acid self-assemblies for the treatment of ulcerative colitis”的研究论文。在本研究中，团队优化了TA和BBR的自组装形式，通过包被HA实现靶向结肠递送，并使用DSS诱导小鼠结肠炎模型，研究自然系统的生物分布行为、作用和机制。团队有针对性的策略为UC治疗提供了一个方便而强大的平台，并揭示了CM组合的新应用模式。

在过去的十年中，UC的发病率在几个国家增加了一倍多，往往需要长期规范用药，以缓解和降低复发率。最近，一系列研究表明从CM中分离出的天然化合物在治疗UC中具有疗效，这些生物活性物质可通过多种机制有效抑制肠道炎症并促进伤口愈合。多药合用是CM最重要的特征之一，黄连中的BBR和黄芩中的生物活性黄酮糖苷黄芩苷可以在水中组装成纳米结构，显示出优异的抑菌活性；TA是一种天然多酚，存在红葡萄酒、红茶、绿茶和许多CM中，其可缓解急性或慢性肠炎症状。目前的研究发现，TA和BBR可在水溶液中自组装成均匀稳定的颗粒（TB），这可归因于两种化合物的氢键形成和π-π堆积的相互作用。

受此启发，团队在带正电荷的TB表面叠加负HA来靶向CD44，并通过HA-CD44相互作用制备了一种新型靶向递送系统（HTB），并将其用于炎性结肠上皮细胞、促炎性巨噬细胞以及DSS诱导结肠炎小鼠模型的治疗。结果证明，HTB可调节氧化应激参数，抑制促炎细胞因子，恢复紧密连接相关蛋白的表达并恢复肠道微生物组的改变，从而对DSS诱导的小鼠急性结肠炎发挥强大的抗炎作用。

图本文图形摘要示意图。

期刊及DOI号

J Adv Res. 2021 Nov 29. doi: 10.1016/j.jare.2021.11.017.

题目

Targeted delivery of Chinese herb pair-based berberine/tannin acid self-assemblies for the treatment of ulcerative colitis

摘要

简介：Ulcerative colitis (UC) is a chronic recurrent idiopathic disease characterized by damage to the colonic epithelial barrier and disruption of inflammatory homeostasis. At present, there is no curative therapy for UC, and the development of effective and low-cost therapies is strongly advocated.

目的：Multiple lines of evidence support that tannic acid (TA) and berberine (BBR), two active ingredients derived from Chinese herb pair (Rhei radix et rhizome and Coptidis rhizoma), have promising therapeutic effects on colonic inflammation. This study aims to develop a targeted delivery system based on BBR/TA-based self-assemblies for the treatment of UC.

方法：TA and BBR self-assemblies were optimized, and hyaluronic acid (HA) was coated to achieve targeted colon delivery via HA-cluster of differentiation 44 (CD44) interactions. The system was systematically characterized and dextran sodium sulfate (DSS)-induced mouse colitis model was further used to investigate the biodistribution behavior, effect and mechanism of the natural system.

结果：TA and BBR could self-assemble into stable particles (TB) and HA-coated TB (HTB) further increased cellular uptake and accumulation in inflamed colon lesions. Treatment of HTB inhibited pro-inflammatory cytokine levels, restored expression of tight junction-associated proteins and recovered gut microbiome alteration, thereby exerting anti-inflammatory effects against DSS-induced acute colitis.

结论：Our targeted strategy may provide a convenient and powerful platform for UC and reveal new modes of application of herbal combinations.