The study aims to investigate the mechanism of Fengshining fecal microbiota transplants in the intervention of rheumatoid arthritis by ultra-performance liquid chromatography-quadrupole/electrostatic field obitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). All animal welfare and experimental procedures followed the regulations of the Medical Ethics Committee of Shanxi University of Chinese medicine. The rats were randomly divided into normal group, model group, fecal microbiota transplantation group and Tripterygium wilfordii polyglycoside group, and the collagen induced arthritis (CIA) was established. The changes of body weight and metatarpodal lesions of rats were evaluated. The serum of rats in each group was analyzed by liquid chromatography-mass spectrometry and metagenomic technology for differential metabolites and microflora. The protein expression levels of Toll-like receptors (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor of kappa B (NF-κB p65) were detected by Western blot. A total of 13 different metabolites, including arachidonic acid, docosahexaenoic acid, 13S-hydroxyoctadecanodienoic acid and L-phenylalanine were screened from serum. Three metabolic pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and arachidonic acid metabolism were identified through pathway enrichment. Metagenomic analysis showed that the abundance of g_Bacteroides, g_Prevotella and p_Actinobacteria in CIA group was higher. The abundance of c_Clostridia, g_Akkermansia and s_Akkermansia_muciniphila in fecal microbiota transplantation group is higher. The hierarchical cluster heat map showed that Akkermansia was negatively correlated with L-phenylalanine; while positively correlated with docosahexaenoic acid. Prevotella was positively correlated with L-phenylalanine. Fecal microbiota transplantation group could significantly inhibit the expression of TLR4, MyD88 and p65 proteins in the synovium of rats (P < 0.01). The anti-rheumatoid arthritis effects of fecal microbiota transplantation group is closely related to the intervention of the metabolism of phenylalanine and arachidonic acid, through Akkermansia, Prevotella and other microorganisms, inhibition the TLR4/MyD88/NF-κB pathway.

Depression is a common emotional disorder that seriously affects people's life and health all over the world. The pathogenesis of depression is complex, and traditional Chinese medicine (TCM) for antidepressants has a good therapeutic effect because of its multi-component, multi-pathway, and multi-target action mode. At present, the anti-depressive mechanism of TCM has not been fully clarified, but it is clear that depression is closely related to metabolic health. Therefore, in order to further explore the anti-depressive mechanism of TCM, this paper proposes research strategies on the anti-depressive mechanism of TCM based on functional metabolomics from the perspective of metabolism, the potential biomarkers of depression are analyzed with the help of multi-omics combined analysis technology, and the functional molecules of TCM for antidepressant are studied. Molecular biology techniques are used to accurately capture the molecular interactions between biomarkers of depression and functional compounds, which identify effective drug targets and further elucidate the biochemical functions and related mechanisms involved in depression metabolic disorders. This paper systematically reviews the research strategies and applications of functional metabolomics in the anti-depressive mechanisms of TCM, expounds on the core value of functional metabolomics, and summarizes the current research status and hot issues of TCM for antidepressants in recent years, providing new methods and new ideas for the study of mechanisms of TCM with the help of functional metabolomics.

Astragalus is a commonly used Chinese medicinal material in traditional Chinese medicine (TCM), and with the increase of planting area in recent years, the damage of Astragalus root rot has worsened year by year, which seriously affecting its quality and yield. Fusarium oxysporum is one of the main pathogens causing root rot in astragalus. In this study, UPLC-Q-TOF-MS based metabolomic approach combined with multivariate statistical analysis were used to analyze the metabolite changes of Astragalus in response to F. oxysporum infection. The results showed that 62 metabolites in the Astragalus had significant changes after inoculation of F. oxysporum. Polar metabolites included 40 flavonoids, 8 saponins, 2 nucleosides, 1 vitamin, 1 organic acid, 1 amino acid; while lipid metabolites included 3 fatty acids, 1 diradylglycerols, 2 lysophosphatidylcholine, 1 lysophosphatidylglycerol, 1 phosphatidylinositol, 1 sterol lipid. Among these differential metabolites, the relative content of flavonoids, vitamin B₂, tryptophan and salicylic acid were increased, while the relative content of saponins were decreased. Correlation analysis showed that the flavonoids were positively correlated with each other, and positively correlated with most lipids, but negatively correlated with most saponins. In addition, studies have shown that F. oxysporum infection is not an influencing factor for the generation of malonyl substitution of flavonoid. This study elucidates the effect of F. oxysporum infection on Astragalus from the perspective of plant metabolism, which provides a basis for exploring the interaction mechanism between the Astragalus and F. oxysporum and further promoting molecular breeding.

Based on the UHPLC-Q-Exactive-MS metabonomics technology, the effect of Hippocampus kuda Bleeker on the life span of Drosophila melanogaster was studied, and the change rule of endogenous metabolites in the aging process of Drosophila melanogaster after the intervention of Hippocampus kuda Bleeker japonicus was explored to clarify the anti-aging mechanism of Hippocampus. The natural aging model of Drosophila melanogaster was used. Different doses of raw Hippocampus and fried Hippocampus were given to observe the effects on the life span, climbing ability, sexual activity, and antioxidant enzyme activity of Drosophila melanogaster. Based on UHPLC-Q-Exactive-MS metabolomics technology, the metabolic profile of the aging Drosophila melanogaster was analyzed using metabonomics technology to explore the mechanism of Hippocampus kuda Bleeker delaying the aging of Drosophila melanogaster. The results showed that raw Hippocampus and crispy Hippocampus (1, 4 mg·mL^-1) could significantly prolong the average life span, median life span and maximum life span of male fruit flies, and significantly improve the climbing ability and sexual vitality of fruit flies. Catalase (CAT) and aldehyde content were increased, while malonaldehyde (MDA) content was decreased. Through metabonomics technology, it was identified that the Hippocampus can significantly recall 16 metabolites and participate in the biosynthesis of phenylalanine, tyrosine and tryptophan, starch and sucrose metabolism, tyrosine metabolism, cysteine and methionine metabolism, and histidine metabolism. The anti-aging mechanism is related to amino acid metabolism and sugar metabolism, which provides a substantial scientific basis for the development and utilization of Hippocampus and clarifying its role in senile diseases. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: SXULL2021028).

In this study, untargeted metabolomics technology based on ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to analyze and identify the overall chemical components of Juniperri Caulis et Folium. Chemical markers for the identification of different Juniperri Caulis et Folium species were screened by integrated principal component analysis and partial least squares discriminant analysis. A total of 58 chemical components were detected and 46 of them were identified, including 26 flavonoids, 8 organic acids and their derivatives, 4 phenylpropanoids, 3 terpenoids, and 5 other components. Among them, methylsyringin and ekersenin were identified for the first time. In the positive ion mode, 12 markers were screened, and in the negative ion mode, 13 markers were screened for species identification. In summary, UPLC-Q-TOF-MS/MS metabonomics technology combined with chemometrics method can effectively reveal the chemical composition differences of different Juniperri Caulis et Folium species, and provide reference for its species identification and quality control.

The objective of this work was to evaluate the anti-fatigue efficacy of Astragali Radix (AR) from the Shanxi Hengshan area and to reveal possible mechanisms by which it relieves fatigue. Efficacy differences between Guangling (GL) and Hunyuan (HY) AR preparations were compared and evaluated, and an ¹H NMR metabolomic technique combined with statistical methods was used to identify the metabolites in different groups of mouse gastrocnemius muscle tissues. The differential metabolites after AR treatments were identified according to VIP and P values and the upstream targets were predicted with the help of Metscape. Cytoscape software was utilized to construct a network map of AR potential anti-fatigue targets. Key differential metabolites were identified based on shared targets and entered into the Metaboanalyst website for pathway enrichment analysis, which led to the preliminary elucidation of the molecular mechanisms. The results showed that intervention with AR can significantly improve the swimming-to-exhaustion time, increase liver glycogen, and reduce urea-nitrogen levels in mice. The difference between GL and HY ARs was relatively small, indicating that the quality of AR produced in the Hengshan area is consistent and stable. The metabolic fingerprints of mouse gastrocnemius muscle tissue extracts were composed of 34 metabolites, and the statistical results showed that 19 differential metabolites were significantly reversed after the Hengshan AR intervention. We found that the anti-fatigue effects of AR in the Shanxi Hengshan area were mainly associated with taurine and hypotaurine metabolism through regulation of GAD1, based on network pharmacological analysis. In conclusion, ¹H NMR metabolomic techniques were combined with network pharmacology to compare and evaluate the quality of Hengshan ARs, and further associate the fatigue relieve with the regulation of taurine metabolism. This provides a theoretical basis for the resource utilization of Hengshan ARs and the development of anti-fatigue-related products. The animal experiments in this study followed the regulations of the Animal Ethics Committee of Shanxi University and passed the ethical review of animal experiments (Approval No. SXULL2021028).

One of the traditional prescriptions for treating lung diseases, Jiegeng decoction (JGT), is still unknown in terms of its chemical makeup and mechanism. In this study, Q-Exactive-Orbitrap MS technology was used to identify the chemical constituents of JGT, and metabolomics was used to examine the effect of JGT on metabolites in the lung tissue of mice with acute lung injury (ALI) model. The potential biomarkers were screened by fold change (FC) > 1.5 or FC < 0.67 and P < 0.05, and enriched for metabolic pathways. A total of 40 compounds, including triterpenoid saponins, flavonoids and glycosides, were identified by mass spectrometry analysis of JGT. All animal experiments were approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2021106). The results showed that JGT improved the lung coefficient, and lung tissue morphology of mice with ALI, lowered the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in bronchoalveolar lavage fluid (BALF), and reduced myeloperoxidase (MPO) content in lung tissue. The metabolomic results showed that JGT could regulate 22 metabolites associated with ALI, among which leukotriene D4, docosapentaenoic acid, hypoxanthine, L-5-oxoproline, and other metabolites were mainly associated with the body′s inflammatory response and oxidative stress, and were enriched in the pathways of glutathione metabolism, purine metabolism, and primary bile acid biosynthesis. This study analyzed the potential mechanism of JGT in the treatment of ALI through metabolomics, providing an important theoretical basis for the clinical application of JGT.

In this study, a combination of metabolomics and network pharmacology was used to study the pharmacodynamic substances and mechanism of action of Yiyi Fuzi powder (YYFZ) on rheumatoid arthritis (RA) rats. The animal experiments were conducted in accordance with the requirements of the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (approval number: TCM-LAEC2021241). The metabolomic analysis using UPLC-Q-TOF/MS technique identified 22 metabolites, including arachidonic acid, tryptophan, linoleic acid, phenylalanine, as significant biomarkers for the treatment of RA with YYFZ, and they were significantly regressed after YYFZ treatment. The analysis of YYFZ blood components also revealed that 11 blood components, including hypaconitine, benzoylhypaconitine, and deoxyaconitine, may be the components that exert direct pharmacological effects in YYFZ in vivo, and further network pharmacological analysis of blood components obtained that YYFZ may exhibit anti-inflammatory effects through acting on PI3K/Akt signaling pathway, estrogen signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway. The results of this study provide implications for the clinical application of YYFZ.

The alterations of serum biological endogenous chemicals in rats with phlegm dampness accumulation syndrome of prehypertension (PHT) were interfered by Banxia Baizhu Tianma decoction (BBT), and the metabolic regulatory pathway of BBT was clarified using serum metabonomics analysis. To replicate the rat model of prehypertension phlegm dampness syndrome, blood pressure, behavioral markers, and serum biochemical markers of rats were collected. BBT's effectiveness in controlling blood pressure and blood lipids was assessed, and changes in endogenous small molecules in rat serum were determined using UPLC-Q-Orbitrap MS metabolic analysis. The results showed that BBT could regulate 9 metabolites, including arachidonic acid, cholic acid, glycodeoxycholic acid, N-adenosyltyrosine, arginine, lysophosphatidylethanolamine (20:0/0:00), lysophospholipid (P-18:0), lysophospholipid (18:0), lysophospholipid (22:5(7Z, 10Z, 13Z, 16Z, 19Z)). MetaboAnalyst was used to analyze the metabolic pathway. There were 7 metabolic pathways closely related to the change of blood pressure in rats, among which arachidonic acid metabolic pathway was the most critical. The metabolism difference foreign body in the model rats tends to return to the normal level, which provides a research basis for the mechanism of BBT from the perspective of metabonomics. This study was approved by the Experimental Animal Welfare Ethics Review Committee of Shandong University of Traditional Chinese Medicine (approval number: SDUTCM20211103001).

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl₄-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks' administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.