Zhu Guoxue, Wu Xiaoqian, Jiang Shujun, Wang Yi, Kong Desong, Zhao Yang, Wang Wang
Department of Neurology, Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Mol Omics. 2022 Aug 15;18(7):666-676. doi: 10.1039/d2mo00074a.
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, , 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.
溃疡性结肠炎（UC）是归类于炎症性肠病（IBD）这一统称下最常见的疾病，对患病患者具有潜在的严重症状和毁灭性后果。在临床研究中， （其中包括丹参酮IIA的活性成分）已被证明具有抗炎作用。然而，丹参酮IIA的抗炎作用及其机制尚不清楚。在本研究中，采用药效学指标评估丹参酮IIA对UC小鼠的影响，如一般状况、疾病活动指数（DAI）、结肠病理形态，并考虑了药效学指标。进一步利用超高效液相色谱-四极杆-静电场轨道阱质谱联用技术（UPLC-Q-Exactive Orbitrap/MS）对小鼠结肠组织进行代谢组学分析，以探索干预途径。结果表明，丹参酮IIA可显著改善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，并升高IL-10的浓度。二十种内源性成分，如牛磺酸、L-谷氨酰胺等，被确认为丹参酮IIA治疗效果的潜在生物标志物。根据相应途径的系统网络分析，丹参酮IIA对小鼠UC的作用主要是通过调节牛磺酸和亚牛磺酸代谢。丹参酮IIA已被证明通过部分调节不稳定网络，对UC小鼠的药效学指标和病理观察具有一定的药理活性。此外，本研究获得的结果可能有助于更好地理解UC疾病的机制和潜在治疗方法。
