Protective effects of Lizhong decoction on ulcerative colitis in mice by suppressing inflammation and ameliorating gut barrier
Protective effects of Lizhong decoction on ulcerative colitis in mice by suppressing inflammation and ameliorating gut barrier
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DOI：
10.1016/j.jep.2020.112919
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发表时间：
2020-09-15
影响因子：
5.4
通讯作者：
Duan, Jin-Ao
中科院分区：
文献类型：
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作者：
Shen, Yumeng;Zou, Junfeng;Duan, Jin-Ao
民族药理学相关性：理中汤为《伤寒论》首载的经方。它已被用于临床治疗溃疡性结肠炎（UC）数千年。本研究的目的：探讨LZD对葡聚糖硫酸钠（DSS）诱导的小鼠溃疡性结肠炎的改善作用，并进一步阐明其作用机制。材料与方法：建立DSS诱导的小鼠溃疡性结肠炎模型，观察LZD口服后的干预作用。采用酶联免疫吸附试验（ELISA）和定量真实的时间聚合酶链反应（qPCR）检测炎症信号通路中关键靶点和小肠紧密连接蛋白的表达。通过抑制髓过氧化物酶（MPO）和超氧化物歧化酶（SOD）的活性，减少一氧化氮（NO）和γ-干扰素等炎性细胞因子的产生，显著减轻UC小鼠结肠炎症（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白细胞介素-β（IL-1 β）和白细胞介素-6（IL-6），以及沿着促进LZD治疗后抗炎细胞因子如白细胞介素-4（IL-4）和白细胞介素-10（IL-10）的产生。LZD能显著下调Toll样受体4（TLR 4）和核因子-κ B的表达（NF-κ B B）mRNA的表达，并上调紧密连接蛋白的表达结论：综上所述，本研究表明，LZD可以通过抑制炎症和改善肠道屏障，为今后临床应用提供了科学依据。
Ethnopharmacological relevance: Lizhong Decoction (LZD) is a classical prescription firstly recorded in "Shanghan Lun". It has been used to clinically treat ulcerative colitis (UC) for thousands of years. However, its mechanism is not clear up to now.Aim of the study: The goal of this study was to assess the amelioration of LZD on dextran sodium sulfate (DSS)-induced colitis in mice and further clarify its mechanism.Materials and methods: The ulcerative colitis model induced by DSS was successfully established and applied to evaluate the intervention effect after oral administration of LZD. Furthermore, the expression of key targets in inflammatory signaling pathways and intestinal tight junction proteins were investigated by enzyme-linked immunosorbent assay (ELISA) and quantitative real time polymerase chain reaction (qPCR) analysis.Results: The results showed that all doses of LZD could notably improve DSS-induced colon lesions, reduce histological scores, prolong colon length and increase body weight. Colonic inflammation in UC mice was significantly alleviated by inhibiting the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), reducing the yield of nitric oxide (NO) and inflammatory cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-beta (IL-1 beta) and interleukin-6 (IL-6), and along with promoting the production of anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10) after LZD treatment. Furthermore, LZD remarkably down-regulated the level of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappa B) mRNA and up-regulated the expression of tight junction proteins (zonula occluden-1, occludin and claudin-1) in UC mice.Conclusion: In summary, this study indicated that LZD could notably improve UC symptoms by suppressing inflammation and ameliorating gut barrier, which provided scientific basis for its clinical application in the future.