| Ganoderma atrum is a famous natural food.Studies have demonstrated that Ganoderma atrum has excellent effects in regulating the immune system,anti-oxidation,anti-aging,ant-tumors and so on.A polysaccharide from Ganoderma atrum(named PSG),the major component was purified from its fruiting bodies.The present study aimed to evaluate protective effects of PSG on acute lung injury(ALI)rats established by lipopolysaccharide(LPS)and its mechanisms.Moreover,UPLC-QTOF/MS metabolomics technology was applied to detect metabolic changes in ALI rats and the intervention effects of PSG.Subsequently,the main results of the present study were listed as follows:1.Anti-inflammatory effects of PSG on LPS-induced ALI rats.The experimental results showed that PSG treatment could regulate the indexes of thymus and spleen of ALI rats to normal levels,significantly increase the counts of WBC,improve lung tissue injury,and reduce levels of NO and IL-1?,TNF-?,and IL-6 in serum and lung tissue homogenates.Accordingly,PSG also could inhibit high-level protein expression of TLR4 and NF-?B in lung tissue.2.PSG pretreatment could effectively improve the disorder of metabolic pathways in serum,urine and lung tissues of ALI rats.The results were analyzed as follows:(1)33 endogenous metabolites were screened and identified in serum of ALI rats,among which taurocholic acid,taurine,LysoPC(18:2)and LysoPC are closely related to inflammatory mediators.Furthermore,analysis of metabolic pathways displayed that these 33 metabolites were mainly involved in glycerophospholipid metabolism,tryptophan metabolism,histidine metabolism,nitrogen metabolism,taurine and taurine metabolism and other pathways.However,PSG intervention could effectively reduce the levels of L-histidine and tryptophan and regulate the levels of PC(20:5)and LysoPE(18:0)to normal levels,revealing the protective effect of PSG on ALI induced by LPS.It was revealed that the protective effect of PSG against LPS-induced ALI rats was mainly achieved by improving glycerophospholipid metabolism,tryptophan metabolism and histidine metabolism in ALI rats.(2)107 differential metabolites were identified from urine.There were 85 differential metabolites between Con and LPS group,among which 32 differential metabolites were significantly improved after PSG intervention.Analysis of metabolic pathways showed that PSG could improve tryptophan metabolism,?-linolenic acid metabolism by regulating conenets of L-Glutamine,L-valine,N-Acetylserotonin,5-Hydroxyindoleacetic acid and ?-linolenic acid.(3)36 differential metabolites were identified in lung tissue,among which 18 metabolites could be effectively ameliorated after PSG treatment.Correspondingly,the treatment of PSG could remedy LPS-induced ALI by improving glycerophospholipid metabolism,linoleic acid metabolism and ?-linolenic acid metabolism.3.Protective effects of PSG on the intestine of LPS-induced ALI rats.The results suggested that PSG could inhibit inflammation in the intestinal tissue,maintain normal tissue morphology,and regulate the levels of IL-1? and IL-10 in the small intestine by affecting the TLR4/NF-?B pathway,thereby balancing the inflammation response in vivo.Simultaneously,PSG also could affect the immune function of the body by regulating the levels of SCFAs in the cecum contents of ALI rats.In addition,phenylpyruvic acid,LysoPC(20:2),PE(18:4/24:1)and PC(24:0/20:4)were found the important biomarkers of cecum contents in the ALI rats by UPLC-Q/TOF-MS technology.PSG pretreatment could restore the disorders of glycerophospholipid metabolism,linoleic acid metabolism,and ?-linolenic acid metabolism by adjusting PC(24:0/20:4)level,but failed for regulation of phenylalanine,tyrosine and tryptophan biosynthesis and phenylalanine metabolism in ALI rats.4.All difference metabolites in ALI rats were integrated.Analysis results illustrated that the occurrence of LPS-induced ALI in rats might be centered on the abnormality of the tricarboxylic acid cycle and lipid metabolism,which may further caused D-glutamine and D-glutamic acid metabolism,histidine metabolism,tryptophan metabolism,phenylalanine metabolism and so on.The treatment of PSG could remedy LPS-induced ALI by regulating the tricarboxylic acid cycle and restoring lipid compounds and amino acids to normal levels. |
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