The application of omics techniques to evaluate the effects of Tanshinone IIA on dextran sodium sulfate induced ulcerative colitis.
The application of omics techniques to evaluate the effects of Tanshinone IIA on dextran sodium sulfate induced ulcerative colitis.
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DOI：
10.1039/d2mo00074a
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发表时间：
2022-06
期刊：
影响因子：
2.9
通讯作者：
Guoxue Zhu;Xiaoqian Wu;Shujun Jiang;Yi Wang;Desong Kong;Yang Zhao;Wang Wang-Wang
中科院分区：
文献类型：
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作者：
Guoxue Zhu;Xiaoqian Wu;Shujun Jiang;Yi Wang;Desong Kong;Yang Zhao;Wang Wang-Wang
溃疡性结肠炎（UC）是炎症性肠病（IBD）中最常见的疾病，对受影响的患者具有潜在的严重症状和破坏性后果。临床研究证明，丹参具有抗炎作用，其中含有丹参酮IIA活性成分。但Tan IIA的抗炎作用及机制尚不清楚。本研究采用药效学指标评价坦IIA对UC小鼠的作用，包括一般情况、疾病活动指数（DAI）、结肠病理形态学和药效学指标。进一步利用UPLC-Q-Exactive Orbitrap/MS技术对小鼠结肠组织进行代谢组学分析，探索干预方法。结果表明，丹参Ⅱ A能明显改善UC小鼠的一般状况，降低DAI评分和组织病理学评分，降低血清中TNF-α、IL-1β、IL-6的浓度，升高IL-10。牛磺酸、L-谷氨酰胺等20种内源性成分被认为是Tan IIA疗效的潜在生物标志物。根据相应途径的系统网络分析，丹参Ⅱ A对小鼠UC的作用主要是通过调节牛磺酸和亚牛磺酸代谢实现的。谭IIA对UC小鼠的药效学指标和病理学观察均显示出一定的药理活性，其作用机制可能是通过部分调节失稳网络实现的。此外，从本研究中获得的结果可能会更好地了解UC疾病的机制和潜在的治疗方法。
Ulcerative colitis (UC) is the most frequent disease classified under the umbrella term inflammatory bowel disease (IBD) with potentially serious symptoms and devastating consequences for the affected patients. In clinical research, Salvia miltiorrhiza Radix et Rhizoma, which includes the active ingredient of Tanshinone IIA, has been proven to have an anti-inflammatory effect. However, Tan IIA anti-inflammatory effect and mechanism are not clear. In this study, the pharmacodynamic index was used to evaluate the effects of Tan IIA on UC mice, such as general conditions, disease activity index (DAI), pathological morphology of the colon and pharmacodynamic indices were taken into account. The UPLC-Q-Exactive Orbitrap/MS technology was further utilized to conduct a metabolomic analysis of mice's colon tissue to explore the intervention approaches. The results demonstrated that Tan IIA could significantly improve the general condition of UC mice, decrease DAI score and histopathological score, reduce the concentrations of TNF-α, IL-1β, IL-6 and increase IL-10 in the serum. Twenty endogenous components, such as taurine, L-glutamine were recognized as underlying biomarkers of the curative effect of Tan IIA. According to the system network analysis of the corresponding ways, the effect of Tan IIA on UC in mice is mainly through the regulation of taurine and hypotaurine metabolism. Tan IIA has been shown to possess definite pharmacological activities on the pharmacodynamic indexes and pathological observations on UC mice by partially regulating the destabilized network. Moreover, the findings acquired from the present study may provide a better understanding of the mechanisms of UC disease and potential therapies.