Metabolomic analysis for the protective effects of mangiferin on sepsis‐induced lung injury in mice

Abstract

This study aimed to investigate the efficacy of mangiferin, including its known antioxidant and anti-inflammatory effects on sepsis-induced lung injury induced by a classical cecal ligation and puncture (CLP) models in mouse using a metabolomics approach. A total of 24 mice were randomly divided into four groups: the sham group was given saline before sham operation. The CLP group received the CLP operation only. HMF and LMF groups were given mangiferin treatment of high dose and low dose of mangiferin, respectively, before the CLP operation. One week after treatment, the mice were sacrificed and their lungs were collected for metabolomics analysis. We developed ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry to perform lung metabolic profiling analysis. With the methods of principal component analysis and partial least squares discriminant analysis, 58 potential metabolites associated with amino acid metabolism, purine metabolism, lipid metabolism and energy regulation were observed to be increased or reduced in HMF and LMF groups compared with the CLP group. Conclusively, our results suggest that mangiferin plays a protective role in the moderation of sepsis-induced lung injury through reducing oxidative stress, regulating lipid metabolism and energy biosynthesis.

Identification of Metabolic Changes in Ileum, Jejunum, Skeletal Muscle, Liver, and Lung in a Continuous I.V. Pseudomonas aeruginosa Model of Sepsis Using Nontargeted Metabolomics Analysis

“…Metabolic changes in the lung after cecal ligation and puncture sepsis have been reported to include alterations in amino acid metabolism, purine metabolism, lipid metabolism, and energy regulation. 92 Metabolites identified in the lung with the present study are involved with aminoacyl-tRNA biosynthesis, valine/leucine/isoleucine biosynthesis, alanine/aspartate/glutamate metabolism, and pantothenate and CoA biosynthesis, including significantly increased valine, alanine, isoleucine, leucine, and threonine and significantly decreased aspartic acid (Figure 5D). In addition, metabolites involved in arginine and proline metabolism included significantly increased fumaric acid, urea, and putrescine and significantly decreased aspartic acid (Figure 5D).…”

“…In addition, metabolites involved in arginine and proline metabolism included significantly increased fumaric acid, urea, and putrescine and significantly decreased aspartic acid (Figure 5D). The significant alterations identified in the present study did not overlap with those in the previous mouse study 92 and may represent differences in the timing of the sepsis (18 hours versus 1 week), the model used (pig versus mouse), or the infection (i.v. P. aeruginosa versus cecal ligation and puncture).…”

CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses

“…Dysregulation of pro-inflammatory cytokines trigger a cytokine storm that may result in tissue damage and organ dysfunction (29). Due to its structural characteristics, lung is the primary failing organ of systemic inflammatory response syndrome (SIRS) (30). Lung injury in septic mice was characterized by alveolar septal thickening, extensive edema, massive infiltration of inflammatory cells, and alveolar congestion/collapse.…”

Liang-Ge decoction ameliorates acute lung injury in septic model rats through reducing inflammatory response, oxidative stress, apoptosis, and modulating host metabolism

“…Moreover, adipose tissue-derived mesenchymal stem cells can suppress the inflammatory responses in the lungs of septic rats by regulating the levels of acetylcholine, spermine, phenylalanine, and threonine (Cui J. et al, 2020). Furthermore, mangiferin can improve lung injury caused by sepsis by inhibiting oxidative stress and regulating the lipid metabolism and energy biosynthesis (Wang et al, 2018;Xu et al, 2020 Lophatheri herba], and can be used for treating the early stage of sepsis. Clinical study revealed that combination treatment of LG and western therapy could significantly suppress the inflammatory response and reduce platelet activation/thrombocytopenia in spetic petients (Wang et al, 2011).…”