Reduning Injection prevents carrageenan-induced inflammation in rats by serum and urine metabolomics analysis

Xia Gao; Jiajia Wang; Xialin Chen; Shanli Wang; Chaojie Huang; Quanchang Zhang; Liang Cao; Zhenzhong Wang; Wei Xiao

doi:10.1016/j.chmed.2022.01.007

Reduning Injection prevents carrageenan-induced inflammation in rats by serum and urine metabolomics analysis

Chin Herb Med. 2022 Sep 15;14(4):583-591. doi: 10.1016/j.chmed.2022.01.007. eCollection 2022 Oct.

Authors

Xia Gao^{1

2

3}, Jiajia Wang^{1

2

3}, Xialin Chen^{1

2

3}, Shanli Wang^{1

2

3

4}, Chaojie Huang^{1

2

3

4}, Quanchang Zhang^{1

2

3}, Liang Cao^{1

2

3}, Zhenzhong Wang^{1

2

3}, Wei Xiao^{1

2

3}

Affiliations

¹ Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China.
² State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China.
³ National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
⁴ China Pharmaceutical University, Nanjing 210009, China.

Abstract

Objective: 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.

Methods: 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.

Results: 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 PGE₂) and pharmacodynamic indicators (IL-6, IL-1β, PGE₂ and TNF-α), which indicated that the selected biomarkers had certain reliability and biological significance.

Conclusion: 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.

Keywords: Reduning Injection; UPLC-Q-TOF/MS; anti-inflammatory effect; metabolomics.