Study on Fu-Fang-Jin-Qian-Cao Inhibiting Autophagy in Calcium Oxalate-induced Renal Injury by UHPLC/Q-TOF-MS-based Metabonomics and Network Pharmacology Approaches.

INTRODUCTION: Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi. Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal injury by inhibiting ROS-mediated autopathy. The mechanism still needs further exploration. Metabonomics is a new subject; the combination of metabolomics and network pharmacology can find pathways for drugs to act on targets more efficiently. METHODS: Comprehensive metabolomics and network pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced renal injury. Based on UHPLC-Q-TOF-MS, combined with biochemical analysis, a mice model of Calcium oxalateinduced renal injury was established to study the therapeutic effect of Fu-Fang-Jin-Qian-Cao. Based on the network pharmacology, the target signaling pathway and the protective effect of Fu- Fang-Jin-Qian-Cao on Calcium oxalate-induced renal injury by inhibiting autophagy were explored. Autophagy-related proteins LC3-II, BECN1, ATG5, and ATG7 were studied by immunohistochemistry. RESULTS: Combining network pharmacology and metabolomics, 50 differential metabolites and 2482 targets related to these metabolites were found. Subsequently, the targets enriched in PI3KAkt, MAPK and Ras signaling pathways. LC3-II, BECN1, ATG5 and ATG7 were up-regulated in Calcium oxalate-induced renal injury. All of them could be reversed after the Fu-Fang-Jin-Qian- Cao treatment. CONCLUSIONS: Fu-Fang-Jin-Qian-Cao can reverse ROS-induced activation of the MAPK signaling pathway and inhibition of the PI3K-Akt signaling pathway, thereby reducing autophagy damage of renal tubular epithelial cells in Calcium oxalate-induced renal injury.

Corrigendum: Phyllanthus niruri L. exerts protective effects against the calcium oxalate-induced renal injury via ellgic acid.

[This corrects the article DOI: 10.3389/fphar.2022.891788.].

Association of serum N-terminal pro-brain natriuretic peptide levels with survival and renal outcomes among elderly patients with acute kidney injury in chronic heart failure.

Background: Elderly patients exhibit a higher incidence of chronic heart failure (CHF). Patients with CHF can develop acute kidney injury (AKI) during follow-up, which can result in poor prognosis. This relationship between kidney dysfunction and levels of N-terminal pro-brain natriuretic peptides (NT-proBNP), with regard to prognosis, is complicated and has rarely been analyzed in elderly patients with CHF. Method: We conducted a retrospective cohort study involving patients with a CHF history aged ≥ 65 years, who experienced an episode of AKI. Kaplan-Meier curves and Cox or logistic proportional hazards regression models were used to evaluate the association between serum NT-proBNP concentrations and mortality or renal recovery by day 90. Results: A total of 1,160 eligible patients with AKI were available for the study. Of this sample, 41.5% of patients died within 90 days of the onset of AKI. Patients with a decreased change in NT-proBNP accompanying the episode of AKI had a lower risk (adjusted OR = 0.56, 95% CI = 0.34-0.91) of more severe AKI (stage 2 and 3 vs. stage 1). The more severe AKI were associated with higher mortality and non-recovery of renal function in elderly patients with CHF, independent of NT-proBNP levels. Elevated levels of baseline lnNT-proBNP (adjusted HR = 1.27, 95% CI = 1.17-1.38) predicted mortality in elderly patients with CHF within 90 days of AKI onset. Patients with a decrease in NT-proBNP accompanying AKI had a lower risk of mortality (adjusted HR = 0.62, 95% CI = 0.48-0.79). However, a decrease in NT-proBNP is a risk factor (adjusted OR = 1.59, 95% CI = 1.02-2.48) for the non-recovery of renal function following AKI-especially in elderly survivors with low baseline NT-proBNP levels. Conclusion: A decreased change in NT-proBNP maybe protective for elderly patients with CHF by improving survival outcomes and preventing severe AKI. However, an excessive decrease in NT-proBNP is a risk factor for the non-recovery of renal function following AKI. Avoiding excessive changes in NT-proBNP may be protective for survival and renal injury prognosis.

Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid.

Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury. Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo. Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment. Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA.

Efficacy of tolvaptan on the short and mid-term prognosis in elderly patients with acute heart failure coexisting with oliguria: A retrospective cohort study.

Background: In patients with acute heart failure (AHF) coexisting with oliguria, high doses of loop diuretics are often ineffective in increasing urine output and may adversely affect the patient's prognosis, especially in elderly patients. We investigated the efficacy of adding tolvaptan (TLV) on improving the prognosis in elderly patients with AHF coexisting with oliguria. Methods: All data for this retrospective cohort study were extracted from the electronic medical record system of the Second Medical Center of Chinese PLA General Hospital from January 2018 to December 2020. Patients diagnosed with AHF coexisting with oliguria were enrolled in this study and were divided into TLV and non-TLV groups based on the use of TLV. The primary outcome was all-cause mortality at 7 and 90-day. The secondary outcomes were the remission of AHF within 7 and 30 days or continued progression of AHF, and new-onset chronic kidney disease (CKD) after 90 days. Cox proportional hazards regression was used to assess the relationships between all-cause mortality and diuretic regimens, demographics, laboratory parameters, comorbidities, and medications. Results: A total of 308 patients met the study criteria for the final statistical analysis, and they had a median age of 91 years (88, 95). The results showed that the addition of TLV was associated with a decreased risk of the 7 and 90-day all-cause mortality in patients with AHF with oliguria [adjusted HR, 95% CI: 0.60 (0.37, 0.98), p = 0.042; 0.56 (0.41, 0.75), p < 0.001, respectively]. Adding TLV significantly increased urine output and decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in 7 days, and alleviated the progression of AHF within 30 days. There were no statistically significant differences between the patients with or without TLV in terms of the occurrence of hypernatremia, the development of hepatic impairment within 30 days, and new-onset CKD after 90 days. Conclusions: This study demonstrated that the addition of TLV was clinically effective in increasing urine output, and had favorable effects on alleviating AHF progression and may reduce the risk of all-cause mortality at 7 and 90-day in elderly patients with AHF with oliguria, and TLV had a good safety profile. Trial registration: http://www.chictr.org.cn/showprojen.aspx?proj=148046, identifier: ChiCTR2200055518.

Metabolic and Network Pharmacological Analyses of the Therapeutic Effect of Grona styracifolia on Calcium Oxalate-Induced Renal Injury.

Grona styracifolia (Osbeck) Merr. (GS), a popular folk medicine, is clinically applied to treat nephrolithiasis. In this study, a urinary metabolic analysis was performed in a mouse model of renal calcium oxalate (CaOx) crystal deposition to identify the differentially altered metabolites in mice with oxalate-induced renal injury and explore the therapeutic mechanisms of GS against nephrolithiasis. Twenty-four mice were randomly divided into the control, oxalate and GS-treated groups. A metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to analyze the metabolic profiles of the urine samples. In addition, network pharmacology analysis was performed with different databases. As a result, the protective effects of GS were verified by measuring biochemical parameters and detecting crystal deposition. Fifteen metabolites were identified as the differentially altered metabolites in mice with crystal-induced renal injury. Most were involved in amino acid and fatty acid metabolism. Thirteen of these metabolites showed a reversal trend following GS treatment. A component-target-metabolite network was further constructed and nine overlapping target proteins of GS and the differentially altered metabolites were discovered. Among these proteins, the expression of estrogen receptor 2 (ESR2) in renal tissues was significantly down-regulated while androgen receptor (AR) expression was obviously increased in the oxalate group compared with the control group. These changes were reversed by the GS treatment. In conclusion, GS exerts its therapeutic effect by regulating multiple metabolic pathways and the expression of ESR and AR in mice with oxalate-induced renal injury.

Integrating metabolomics and network pharmacology to explore Rhizoma Coptidis extracts against sepsis-associated acute kidney injury.

Sepsis remains the most common cause of acute kidney injury (AKI) in critically ill patients, increasing the risk of in-hospital and long-term death. Rhizoma Coptidis (RC), a classical traditional Chinese herb, exhibits anti-inflammatory and antioxidant properties in various diseases including sepsis. This study aimed to investigate the protective effects of RC extracts (RCE) against sepsis-associated acute kidney injury (SA-AKI) and explore the underlying mechanisms with metabolomics-based network pharmacology. The results showed that RCE improved renal function and histological injury and decreased reactive oxygen species (ROS) production in SA-AKI. Using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), 25 differential metabolites were identified that had a close connection with the pathological processes of SA-AKI and the effects of RCE. Afterward, a compound-metabolite-target-disease network was constructed and 17 overlapping target proteins of the components of RCE, the differential metabolites, and the disease-related genes were discovered. Among these overlapping target proteins, RCE increased the nuclear translocation of nuclear factor-erythroid 2-related factor-2 (Nrf2), the protein expression of heme oxygenase-1 (HO-1), the mRNA expression of peroxisome proliferator activated receptor α (PPARα) and reduced nitric oxide synthase 2 (NOS2) activity. In addition, molecular docking revealed that both berberine and quercetin could bond with NOS2 and PPARα, respectively. Therefore, RCE demonstrated protective effects for SA-AKI through the regulation of metabolism and different signaling pathways.

A stop-flow comprehensive two-dimensional HK-2 and HK-2/CIKI cell membrane chromatography comparative analysis system for screening the active ingredients from Pyrrosia calvata (Bak.) Ching against crystal-induced kidney injury.

Crystal-induced kidney injury (CIKI) is the fundamental pathological change during nephrolithiasis, although the molecular mechanism is still unclear. Pyrrosia calvata (Bak.) Ching has been used in folk medicine to treat urolithiasis for years. To clarify the pharmacodynamic substances and the mechanism of its antiurolithiasis effects, in this study, a novel, stop-flow, comprehensive, two-dimensional (2D) HK-2 and HK-2/CIKI cell membrane chromatography (CMC) comparative analysis system was developed to screen for the potential active ingredients from Pyrrosia calvata (Bak.) Ching against CIKI. The comprehensive 2D CMC comparative analysis system showed satisfactory selectivity, and eight ingredients were screened and identified by this system. Among them, mangiferin exhibited higher affinity for the HK-2/CIKI CMC column than the HK-2 CMC column and was selected for further efficacy verification. Cell proliferation assays showed that mangiferin could protect HK-2 cell viability after stimulation with sodium oxalate (NaOX). Additionally, in a rodent model of CIKI, mangiferin decreased the deposition of calcium oxalate (CaOX) crystals in mouse kidneys, alleviated the pathological damage to kidney tissue, and inhibited the upregulation of OPN, MCP1, and CD44 expression caused by CaOX crystals. The established comprehensive 2D CMC comparative analysis system can be applied to screen active ingredients with disease specificity from traditional Chinese medicine (TCM) and is suitable for other cell models.

Fu-Fang-Jin-Qian-Cao herbal granules protect against the calcium oxalate-induced renal EMT by inhibiting the TGF-ß/smad pathway.

CONTEXT: Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown. OBJECTIVE: This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury. MATERIALS AND METHODS: 60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor ß (TGF-ß)/Smad pathway were conducted on renal tissues. RESULTS: Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II. CONCLUSION: FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-ß/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.

SIRT1 gene polymorphisms are associated with nondiabetic type 1 cardiorenal syndrome.

Type 1 cardiorenal syndrome (CRS1) is characterized by acute cardiac disease (e.g., acute heart failure [AHF]), leading to acute kidney injury. Sirtuin 1 (SIRT1), an NAD+ -dependent deacylase, has been found to be associated with CRS1. To confirm whether a correlation exists between SIRT1 variants and the risk of CRS1, the association between the prevalence of CRS1 and single-nucleotide polymorphisms (SNPs) within the SIRT1 gene was investigated in AHF patients. A total of 316 Chinese AHF participants (158 patients with CRS1 and 158 age- and sex-matched controls) were recruited for the present observational study to investigate the association between nine common SIRT1 SNPs (i.e., rs7895833 G > A, rs10509291 T > A, rs3740051 A > G, rs932658 A > C, rs33957861 C > T, rs7069102 C > G, rs2273773 T > C, rs3818292 A > G, and rs1467568 A > G) and the susceptibility to CRS1. Significant differences in genotype distribution between the control and CRS1 groups were found for rs7895833 and rs1467568. After applying a Bonferroni adjustment, the A allele of rs7895833 was still found to be protective (p = 0.001; odds ratio [OR] = 0.77) against CRS1 in this study population. The AA genotype of rs7895833 and the GA genotype of rs1467568 were associated with a significantly reduced risk of CRS1 (OR = 0.23 and 0.49, respectively). rs7895833 and rs1467568 were further analyzed as a haplotype, and the GA haplotype (rs7895833-rs1467568) exhibited a significant association with CRS1 (p = 0.008), while the AA haplotype showed a significant protective effect (p = 0.022). Our study showed that SIRT1 rs7895833 and rs1467568 polymorphisms had a significant effect on the risk of developing CRS1 in a population in China.

Metabolomic analysis reveals a protective effect of Fu-Fang-Jin-Qian-Chao herbal granules on oxalate-induced kidney injury.

Nephrolithiasis is one of the world's major public health burdens with a high incidence and a risk of persistent renal dysfunction. Fu-Fang-Jin-Qian-Chao granules (FFJQC), a traditional Chinese herb formula, is commonly used in treatment of nephrolithiasis. However, the therapeutic mechanism of FFJQC on kidney stone has still been a mystery. The objective of the present study is to explore the therapeutic mechanism of FFJQC on kidney injury and identify unique metabolomics patterns using a mouse model of kidney stone induced by a calcium oxalate (CaOx) deposition. Von Kossa staining and immuno-histopathological staining of osteopontin (OPN), cluster of differentiation 44 (CD44) and calbindin-D28k were conducted on renal sections. Biochemical analysis was performed on serum, urine, and kidney tissues. A metabolomics approach based on ultra-HPLC coupled with quadrupole-TOF-MS (UHPLC-Q-TOF/MS) was used for serum metabolic profiling. The immunohistopathological and biochemical analysis showed the therapeutic benefits of FFJQC. The expression levels of OPN and CD44 were decreased while calbindin-D28k increased after the CaOx injured mice were treated with FFJQC. In addition, total of 81 serum metabolites were identified to be associated with protective effects of FFJQC on CaOx crystal injured mice. Most of these metabolites were involved in purine, amino acid, membrane lipid and energy metabolism. Potential metabolite biomarkers were found for CaOx crystal-induced renal damage. Potential metabolite biomarkers of CaOx crystal-induced renal damage were found. FFJQC shows therapeutic benefits on CaOx crystal injured mice via regulation of multiple metabolic pathways including amino acids, purine, pyrimidine, glycerolipid, arachidonic acid (AA), sphingolipid, glycerophospholipid, and fatty acid.

Association of sirtuin 1 gene polymorphisms with nephrolithiasis in Eastern chinese population.

Sirtuin 1 (SIRT1), an NAD+-dependent deacylase, has been identified to be associated with renal tubular inflammatory conditions and metabolic disorders, which are risk factors of nephrolithiasis. To further confirm the role of the SIRT1 in kidney stone formation, the expression of SIRT1 was analyzed based on a mouse model and the genetic polymorphisms of SIRT1 gene was compared between patients with kidney stones and controls. The calcium oxalate (CaOx) crystal-induced renal injury model was established to analyzed the expression of SIRT1 in the kidney tissue of both wild-type and ApoE(-/-) mice. And a total of 430 Eastern Chinese subjects (215 patients with nephrolithiasis and 215 age- and gender-matched controls) were recruited for the present study to investigate the associations between 6 common single nucleotide polymorphisms (SNPs) (i.e., rs10509291, rs3740051, rs932658, rs33957861, rs3818292 and rs1467568) in the SIRT1 gene and the incidence of kidney stones. Pairwise linkage disequilibrium and the haplotypes of the 6 SNPs were also analyzed. The genotypes of SIRT1 gene polymorphisms were analyzed by a Snapshot assay. Reduced expression of SIRT1 was observed in the kidney of the mice in the crystal group, revealing the potential role of SIRT1 in the nephrolithiasis. However, we did not find a significant association between the 6 SNPs of the SIRT1 gene and kidney stone formation in the Eastern Chinese population.

The mechanism of the preventive effect of Shen'an capsule on the calcium oxalate crystal-induced early renal injury based on metabolomics.

Kidney stone disease is a worldwide metabolism-associated disorder with a high incidence of renal dysfunction. However, effective methods to prevent crystalline nephropathy are still lacking owing to the absence of aetiological research. Shen'an (SA) capsules are prepared from Chinese medicinal compounds and are considered a promising treatment for the prevention of crystal-induced renal injury. In this study, 24 mice were randomly divided into four groups: saline, oxalate, SA-treated (via preventive administration) and SA-only groups. A metabolomics analysis based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to explore the plasma metabolic profiles among the different groups. The amount of crystal deposition and the decline in kidney function were significantly alleviated by the use of SA capsule. A total of 24 metabolites that showed a reversal trend following SA capsule administration were identified as plasma biomarkerss of the preventive effects of SA capsules on crystal-induced renal injury. Most of these metabolites were involved in the metabolisms of lipid metabolism, energy metabolism, glutathione metabolism and vitamin metabolism. In conclusion, SA capsules exert a preventive effect in mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways.

Exploring the Therapeutic Mechanism of Desmodium styracifolium on Oxalate Crystal-Induced Kidney Injuries Using Comprehensive Approaches Based on Proteomics and Network Pharmacology.

Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb.) Merr (DS) has been applied clinically to alleviate crystal-induced kidney injuries, but its effective components and their specific mechanisms still need further exploration. This research first combined the methods of network pharmacology and proteomics to explore the therapeutic protein targets of DS on oxalate crystal-induced kidney injuries to provide a reference for relevant clinical use. Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were established. Proteins differentially expressed between the oxalate and control groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The common differential proteins of the three models were further analyzed by molecular docking with DS compounds to acquire differential targets. The inverse docking targets of DS were predicted through the platform of PharmMapper. The protein-protein interaction (PPI) relationship between the inverse docking targets and the differential proteins was established by STRING. Potential targets were further validated by western blot based on a mouse model with DS treatment. The effects of constituent compounds, including luteolin, apigenin, and genistein, were investigated based on an oxalate-stimulated HK-2 cell model. Results: Thirty-six common differentially expressed proteins were identified by proteomic analysis. According to previous research, the 3D structures of 15 major constituents of DS were acquired. Nineteen differential targets, including cathepsin D (CTSD), were found using molecular docking, and the component-differential target network was established. Inverse-docking targets including p38 MAPK and CDK-2 were found, and the network of component-reverse docking target was established. Through PPI analysis, 17 inverse-docking targets were linked to differential proteins. The combined network of component-inverse docking target-differential proteins was then constructed. The expressions of CTSD, p-p38 MAPK, and p-CDK-2 were shown to be increased in the oxalate group and decreased in kidney tissue by the DS treatment. Luteolin, apigenin, and genistein could protect oxalate-stimulated tubular cells as active components of DS. Conclusion: The potential targets including the CTSD, p38 MAPK, and CDK2 of DS in oxalate-induced kidney injuries and the active components (luteolin, apigenin, and genistein) of DS were successfully identified in this study by combining proteomics analysis, network pharmacology prediction, and experimental validation.

Decision-making in a bisexual line and a thelytokous Wolbachia-infected line of Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae) regarding behavior toward their hosts.

BACKGROUND: The use of thelytokous Wolbachia-infected Trichogramma (parasitic wasps) has long been considered as a way to enhance the efficacy of biocontrol. However, Wolbachia can affect the host physiology. We compared decision-making between bisexual and thelytokous Wolbachia-infected lines of Trichogramma dendrolimi Matsumura regarding behavior toward fresh and old eggs of Corcyra cephalonica at 25 ± 1 °C and 70 ± 5% relative humidity. RESULTS: The behavioral patterns and sequences of the two lines were basically the same. The durations of various behavioral patterns and values of fitness indicators of the bisexual line on fresh eggs were generally significantly shorter and better, respectively, than on old eggs, whereas the thelytokous line behaved similarly toward the two types of eggs, and differences in most fitness indicators between fresh and old eggs were not significant. On fresh eggs, the durations of various behaviors in the bisexual line were generally significantly shorter than in the thelytokous line and the fitness indicators were generally significantly better. CONCLUSION: Wolbachia affected the fitness of T. dendrolimi negatively. The potential of the thelytokous line as a biocontrol agent would not be as good as that of the bisexual line when decision-making only is considered. Therefore, further evaluations need to be carried out before the thelytokous line can be used in practical biocontrol. © 2018 Society of Chemical Industry.

Plasma metabolomic profile and potential biomarkers for missed abortion.

A missed abortion (MA) is an in utero death of the embryo or fetus before the 20th week of gestation with retained products of conception, and this condition is currently common in China. In order to discover novel biomarkers for MA, ultrahigh performance liquid chromatography was applied to study plasma metabolite profiles for 33 patients with MA and 29 control subjects. Thirty-seven differential plasma metabolites were found to discriminate between the two groups in the initial cohort (15 subjects with MA and 15 healthy controls). The feasibility of using these potential biomarkers to predict MA was further evaluated in the validation cohort (18 subjects with MA and 14 healthy controls) and 15 had an area under the receiver operating characteristic curve of >0.80, making them satisfactory. Tryptophan metabolism and sphingolipid metabolism were identified as important potential target pathways for MA using metabolic pathway impact analysis. Furthermore, three of the 15 satisfactory metabolites (glyceric acid, indole and sphingosine) were combined to establish a predictive model with 100% sensitivity and 100% specificity in the validation cohort. Taken together, these results suggest that MA results in significant disturbance of metabolism and those various novel biomarkers have satisfactory diagnostic and predictive power for MA.