OBJECTIVE: Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury. METHODS: To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity. RESULTS: Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism. CONCLUSION Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.
Animals ; Mice ; Polygonum/chemistry* ; Lipidomics ; Liver ; Lipids/pharmacology* ; Glycerophospholipids/pharmacology* ; Chemical and Drug Induced Liver Injury/metabolism*

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.
Rats ; Animals ; Periploca ; Cysteine ; Cytidine Diphosphate Choline ; Network Pharmacology ; Phosphorylcholine ; Metabolomics ; Arthritis, Rheumatoid/drug therapy* ; Biomarkers ; Glycerophospholipids ; Methionine ; Purines ; Chromatography, High Pressure Liquid

Phospholipase D (PLD) is an enzyme involved in signal transduction and widely distributed in mammalian cells. The signal transduction pathways and role for phospholipid metabolism during hormonal response in cortical collecting duct remain partly undefined. It has been reported that dexamethasone increases transepithelial transport in M-1 cells that are derived from the mouse cortical collecting duct. We investigated the expression and activity of PLD in M-1 cells. Basal PLD activity of M-1 cells cultured in the presence of dexamethasone (5 microM) was higher than in the absence of dexamethasone. Dexamethasone and ATP activated PLD in M-1 cells but phorbol ester did not stimulate PLD activity. Vasopressin, bradykinin, dibutyryl cyclic AMP, and ionomycin were ineffective in activating PLD of the cells. The PLD2 isotype was detected by immunoprecipitation but PLD1 was not detected in M-1 cells. Addition of GTPgammaS and ADP-ribosylation factor or phosphatidylinositiol 4,5-bisphosphate to digitonin-permeabilized cells did not augment PLD activity. In intact cells PLD activity was increased by sodium oleate but there was no significant change between dexamethasone treated- and untreated cells by oleate. These results suggest that at least two types of PLD are present in M-1 cells and PLD plays a role in the corticosteroid-mediated response of cortical collecting duct cells.
Animal ; Biological Transport/drug effects ; Dexamethasone/pharmacology* ; Dose-Response Relationship, Drug ; Drug Interactions ; Glycerophospholipids/analysis ; Isoenzymes/drug effects ; Kidney Cortex/cytology ; Kidney Tubules, Collecting/drug effects* ; Kidney Tubules, Collecting/cytology ; Mice ; Mice, Transgenic ; Oleic Acid/pharmacology ; Phospholipase D/drug effects*

This study was to report the effect of Tangshen Formula on phospholipids metabolism in diabetic nephropathy patients. A normal phase-HPLC-TOF/MS method was used in this study for the determination of seven species of phospholipids in human plasma. Then, the concentration changes of potential phospholipids biomarkers were discussed in diabetic nephropathy phase III and phase IV patients among different groups, including before and 3, 6 months after administration of Tangshen Formula. Significant increases of PE750, PI885, PC792, PC826, PC830, PC854 and PC802 levels were observed 6 months after administration of Tangshen Formula and conventional western medicine, as well as a decrease of LPC540 level, when compared with those before medication. Concentrations of all the potential phospholipids biomarkers showed a tendency towards normal levels; however, both the improvement degree and onset time of these compounds were not same. Additionally, Tangshen Formula treatment based on conventional western medicine treatment was more efficient in adjusting the levels of these compounds when compared with western medicine treatment alone, especially for the phase IV patients. These results indicated that Tangshen Formula was capable in regulating and improving phospholipids metabolism in diabetic nephropathy patients, which may be related with the direct or indirect inhibition of protein kinase C pathway and the corresponding reduction of phospholipase A2 activity. Therefore, Tangshen Formula may be used as an effective drug for diabetic nephropathy therapy, at least as an adjunctive therapeutic drug.
Diabetic Nephropathies ; blood ; metabolism ; Double-Blind Method ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Glycerophospholipids ; blood ; Humans ; Lysophosphatidylcholines ; blood ; Phospholipases A2 ; metabolism ; Phospholipids ; blood ; classification ; Plants, Medicinal ; chemistry ; Protein Kinase C ; metabolism ; Signal Transduction ; Sphingomyelins ; blood