Lu Dangshen, a traditional authentic medicinal material of Codonopsis Radix is mainly produced in Shangdang (Changzhi) area of Shanxi Province. Baitiao Dangshen is mainly produced in Gansu Province. Codonopsis Radix contains many kinds of components such as phenylpropanoids, polyalkynes, alkaloids, terpenes, fatty acids, flavonoids, and so on. At present, the effect of producing areas on its chemical compositions has not been systematically studied. This study analyzed the differences of metabolites among Codonopsis pilosula from different producing areas by UPLC-HRMS. PCA, OPLS-DA coupled with Thermo mzcloud online and local databases were used to compare the overall differences of metabolites among Codonopsis pilosula from different producing areas, and the chemical constituents were identified to further screen and find out the different metabolites and analyze the metabolic pathways by information retrieval in HMDB, PubChem, Chemspider and KEGG databases. The results showed that 72 differential metabolites were identified in this study. There were 15 kinds of up-regulated and 57 kinds of down-regulated metabolites of Lu Dangshen compared with Baitiao Dangshen. The top 30 metabolic pathways were analyzed by KEGG enrichment, and the most important metabolic pathways were phenylpropanoid biosynthesis, which was demonstrated that phenylpropanoid biosynthesis pathway and related intermediate metabolites could be used as the characteristics of distinguishing Lu Dangshen from different habitats of Codonopsis pilosula. The present study provided a basis for analyzing the influence of producing areas on the chemical components of Codonopsis pilosula and reasonably evaluating the quality of Codonopsis Radix, and also provided a new idea for expounding the authenticity of Lu Dangshen.

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).

The pharmacodynamic substance of traditional Chinese medicine (TCM) is an important basis for its mechanism and quality control, and also a key scientific issue for the inheritance and development of TCM. However, the complex characteristics of multi-component, multi-target and integrity of TCM, as well as the limitations of modern scientific research technical methods, have brought great challenges to the research. The interactions between Chinese medicine and intestinal flora provide us with a new idea. Based on the effective role of TCM and the hypothesis of correlation between intestinal flora and disease, the research on the material basis and mechanism of action of TCM based on intestinal metabolomics mostly explored the relationship between microflora and host phenotype, gradually deepening, and finally focused on the relationship between intestinal strains and molecular levels. This paper summarized the research ideas and key technologies of this model, in order to provide reference for the application of this model.

This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

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.

The purpose of this study was to investigate the effects of ethanol extract of Scutellaria baicalensis Georgi (SGE) on endogenous metabolites in toes of rats with inflammatory pain induced by complete Freund's adjuvant (CFA) based on ¹H NMR metabolomics, which would provide foundation for revealing the effects and mechanisms of SGE in improving inflammatory pain. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2022062). The rats model of inflammatory pain was induced by subcutaneous injection of CFA (0.1 mL), and the effect of low, medium and high doses of SGE (1.5, 3, 6 g·kg^-1) on inflammatory pain were explored. The effects of SGE on relieving inflammatory pain was evaluated by mechanical nociceptive thresholds (MNTs) test. Western blot was used to detect the effects of SGE on protein expression of cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB) and phospho-NF-κB (p-NF-κB). ¹H NMR metabolomics was used to analyze the regulatory effects of SGE on endogenous metabolites in the toes of rats with inflammatory pain. The results showed that SGE (6 g·kg^-1) could significantly relieve CFA-induced inflammatory pain, and also notably inhibit the protein expression of COX-2, NF-κB and p-NF-κB. SGE could markedly reverse the changes of 8 differential metabolites, such as glycine, glutamine, succinate, phosphorylcholine, etc. The metabolites were involved in eight metabolic pathways, such as glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, glutathione metabolism, glycerophospholipid metabolism. These results suggest that SGE may relieve inflammatory pain by regulating NF-κB signaling pathway and metabolic abnormality.

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.

On the basis of the qualitative preparation quality markers of Zhibao Sanbian Wan (ZBSBW), we screened out the quantitative markers and evaluated the content consistency of ZBSBW. A method capable of simultaneously determining 34 compounds in ZBSBW was established based on HPLC-MS/MS, and 16 batches of ZBSBW were simultaneously analyzed by this method. Furthermore, we explored a general strategy for analyzing the component migration in preparation, plasma, brain tissue and cerebrospinal fluid. The methodological investigation was confirmed by linear range, recovery (85.10%-105.07%), precision (RSD: 1.37%-4.58%), stability, and repeatability (3.00%-12.45%), the established method was suitable for the detection and quantification of the compounds in ZBSBW. The contents of compounds in ZBSBW were all lower than 1 mg·g^-1, and the contents and daily dose of nystose were the highest, followed by echinacoside, paeoniflorin, osthole and paeonol. The results of systematic clustering showed that the contents were consistent for ordinary preparations of ZBSBW. The principal component analysis showed that the components of berberine, ginsenoside Re, ginsenoside Rg1, pinoresinol diglucoside and tenuifolin had large variation, which contributed significantly to the grouping. The contents of echinacoside, verbascoside, polygalaxanthone Ⅲ, β-ecdysterone, osthole, alisol B 23-acetate, liquiritin and glycyrrhizic acid were stable from batch to batch. The animal experiment results showed that osthole, paeonol and liquiritin in ZBSBW could be absorbed into the blood and enter the brain tissue by passing through the blood-brain barrier. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. 2020B071). The above compounds contributed the quantitative preparation quality markers of ZBSBW. In conclusion, the HPLC-MS/MS method established in this study was sensitive, accurate and rapid, and could be used for simultaneous quantification of 34 compounds and content consistency evaluation of multiple batches of preparations in ZBSBW. The result provided a methodological basis for the screening of quantitative preparation quality markers and material basis research of ZBSBW.

This study aimed to explore the effects of Ziziphi Spinosae Seme (ZSS) and Fried Ziziphi Spinosae Semen (FZSS) on metabolites and intestinal flora structure in insomnia mice by combining metabolomics analysis and 16S rRNA gene sequencing. Animal experimentation was approved according to the Committee on the Ethics of Animal Experiments of Shanxi University of Chinese Medicine (approval number: 2021DW172). The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia mice with administration of ZSS and FZSS for 5 days, respectively. Then pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of ZSS and FZSS. The metabolic profile of serum from insomnia mice was analyzed by UPLC-Q-Orbitrap MS. Different metabolites were screened combined with multivariate statistical analysis. The relevant metabolic pathways and networks were constructed by MetaboAnalyst 5.0. Intestinal flora changes were detected by 16S rRNA sequencing technology. Animal study indicated that, compared to PCPA-induced insomnia model, ZSS and FZSS shortened the sleeping latency and increased the sleeping duration. The serum metabolomics results showed that, there are 36 potential biomarkers associated with insomnia were identified. Compared with the model group, 25 and 27 differential metabolites were identified in the ZSS and FZSS groups, respectively. Both ZSS and FZSS groups could significantly adjust to the common 20 differential metabolites. A total of 10 pathways are closely related to insomnia, which including amino acid metabolism, energy metabolism and lipid metabolism. 5 metabolic pathways are shared in ZSS and FZSS, including phenylalanine, tyrosine and tryptophan biosynthesis, cysteine and methionine metabolism and so on. Arachidonic acid metabolism is the unique metabolic pathway for ZSS to improve sleep; 3 metabolic pathways including glutamate and glutamine are the unique regulatory pathway for FZSS to improve sleep. PCoA analysis showed that the structure of ZSS and FZSS recovered to blank group, ZSS and FZSS can decrease the abundance of Pvotella and increase the abundance of Lactobacillus. LEfSe and correlation analysis between metabolites and differential intestinal flora showed that kynurenic acid, L-glutamic acid, D-proline are significantly positively associated with Gammaproteobacteria in ZSS and 5-HT, acetylcholine, L-methionine are significantly positively associated with Lactobacillus in FZSS. In conclusion, both ZSS and FZSS can influence metabolic pathways such as amino acids, energy and lipids and regulate the structure of intestinal flora, and then play a part in treating insomnia. However, ZSS and FZSS improve the quality of sleeping by regulating different metabolic pathways and regulating gut microbiota structure. The results of this study provide an experimental basis for illustrating the action mechanism of ZSS and FZSS in treating insomnia and provide a scientific basis for clinical rational medication guidance.

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.