Gao Xia, Wang Jiajia, Chen Xialin, Wang Shanli, Huang Chaojie, Zhang Quanchang, Cao Liang, Wang Zhenzhong, Xiao Wei
Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China.
State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China.
Chin Herb Med. 2022 Sep 15;14(4):583-591. doi: 10.1016/j.chmed.2022.01.007. eCollection 2022 Oct.
To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level.
Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators.
A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE) and pharmacodynamic indicators (IL-6, IL-1β, PGE and TNF-α), which indicated that the selected biomarkers had certain reliability and biological significance.
RDN has a good regulation of the metabolic disorder of endogenous components in carrageenan-induced inflammatory rats. And its anti-inflammatory mechanism is mainly related to the regulation of amino acid and lipid metabolism. This research method is conducive to the interpretation of the overall pharmacological mechanism of Chinese medicine.
通过从整体代谢水平分析角叉菜胶诱导的炎症模型的潜在生物标志物和代谢途径，阐明热毒宁注射液（RDN）的抗炎机制。
采用角叉菜胶建立大鼠炎症模型。运用超高效液相色谱-四极杆飞行时间串联质谱（UPLC-Q-TOF/MS）检测并分析角叉菜胶诱导的炎症大鼠血清和尿液中内源性代谢物的变化。结合多变量分析和数据库分析，筛选并鉴定与炎症相关的潜在生物标志物，以分析可能的代谢途径。通过代谢网络分析以及与药效学指标的相关性分析，验证这些生物标志物的可靠性和生物学意义。
通过多变量分析和代谢物数据库共筛选并鉴定出16种潜在生物标志物，其中13种可被RDN调节。代谢途径分析显示，组氨酸代谢、鞘脂代谢和酪氨酸代谢受到极大干扰。其生物标志物涉及尿刊酸、鞘氨醇和去甲肾上腺素，RDN治疗后均呈现回调趋势。这三种生物标志物与一些已知的炎症相关小分子（组胺、花生四烯酸、白三烯B4和前列腺素E）以及药效学指标（白细胞介素-6、白细胞介素-1β、前列腺素E和肿瘤坏死因子-α）具有一定相关性，表明所筛选的生物标志物具有一定的可靠性和生物学意义。
RDN对角叉菜胶诱导的炎症大鼠内源性成分的代谢紊乱具有良好的调节作用。其抗炎机制主要与氨基酸和脂质代谢的调节有关。该研究方法有助于阐释中药的整体药理机制。
