Traditional Chinese Medicine (TCM) Glycobiology and TCM glyco-engineering represent an emerging interdisciplinary field that integrates the holistic perspective of TCM with modern glycoscience, aiming to establish a new paradigm for glycoscience research with Chinese characteristics. This article systematically elaborates how TCM glycobiology, with the “syndrome-glycome correlation” as its core, interprets the scientific connotation of the glyco-based material basis of TCM theories. Meanwhile, it expounds that TCM glyco-engineering realizes a technical system for the precise synthesis, structural modification and full-process quality control of saccharide components through technologies such as synthetic biology, artificial intelligence and green preparation. Furthermore, the article explores the value of this field in bridging the concepts of traditional Chinese and Western medicine, promoting the industrial upgrading of traditional Chinese medicines, and prospects its development paths in theoretical framework construction, technological innovation and internationalization. This review provides a systematic approach for the cross-integration of TCM modernization and glycoscience, and plays a guiding role in leading the development of this distinctive discipline.
Objective: Mogrosides, a group of cucurbitane-type triterpenoid glycosides derived from Siraitia grosvenorii, are widely recognized as natural sweeteners with additional health-promoting properties. Among them, mogroside V is the most abundant component in commercial extracts; the limited natural occurrence of rare mogrosides severely restricts their functional investigation and industrial utilization. Microbial biotransformation is considered a promising strategy for the selective and efficient preparation of rare mogrosides under mild conditions. The objective of this work is to screen for functional fungal strains with inherent substrate adaptability in the natural cultivation environment of S. grosvenorii and to systematically evaluate their ability to biotransform mogroside V directionally into rare mogrosides with high efficiency and specificity. Methods: The isolated strains were preliminarily screened for mogroside V biotransformation activity using liquid fermentation systems with mogroside V as the sole substrate. Thin-layer chromatography (TLC) was employed for rapid qualitative analysis, and high-performance liquid chromatography (HPLC) was used for the accurate identification and quantification of transformation products. Strains exhibiting stable, directional, and efficient hydrolytic activity toward mogroside V were selected as dominant strains. Scanning electron microscopy (SEM) was also employed to observe the morphology of the selected strains. Results: Two fungal strains capable of efficiently converting mogroside V were successfully obtained through activity-based screening. Strain B4 was identified as Trichoderma asperellum based on morphological characteristics and molecular identification. This strain selectively converts mogroside V into mogroside IIA as the predominant product through specific glycosidic bond hydrolysis. Strain E212 was identified as Mucor circinelloides and is capable of efficiently converting mogroside V into mogroside IIIE with high specificity. Optimization experiments revealed that both strains achieved optimal catalytic performance at an incubation temperature of 25℃. The highest transformation efficiency of strain B4 was observed at an initial pH of 5.0, whereas strain E212 exhibited optimal activity at pH 6.0. For both strains, an initial mogroside V concentration of 2.5 g/L was determined to be optimal. Under optimized conditions, the yield of mogroside IIA produced by strain B4 reached 87.6%, while the yield of mogroside IIIE produced by strain E212 reached 83.0%, demonstrating the high efficiency and practical potential of the selected strains. Conclusion: Functional fungal strains capable of efficiently and selectively biotransforming mogroside V were successfully obtained from the natural ecological environment associated with S. grosvenorii cultivation. The directional hydrolysis behavior, high product yields, and mild fermentation conditions highlight the advantages of microbial biotransformation for the preparation of rare mogrosides. The results provide valuable microbial resources and a reliable technical foundation for further studies on enzymatic mechanisms, process optimization, and the sustainable industrial production of rare mogrosides from S. grosvenorii.
Baicalin is the core bioactive component of Scutellaria baicalensis, exhibiting broad pharmacological activities. Therefore, the efficient and stable production and preparation of baicalin hold significant importance. Traditional chemical synthesis methods involve cumbersome steps and high costs, while plant extraction methods suffer from unstable yields and quality due to environmental factors. With the advancement of synthetic biology, synthesizing baicalin using microbial cell factories has emerged as an effective solution to address resource constraints. This paper systematically reviews the pharmacological activities of baicalin and its synthetic pathways within plants, particularly the root-specific flavonoid synthesis pathway initiated by Coenzyme A ligase ( SbCLL-7), elucidating the functions and regulatory mechanisms of key rate-limiting enzymes, such as Pinocetin chalcone synthase (SbCHS-2), cytochrome P450 hydroxylase (SbCYP82D), and UDP-glucuronosyltransferases ( SbUGAT). Furthermore, it summarizes examples of baicalin synthesis through metabolic engineering strategies, including intermediate-source assembly and precursor optimization, using microbial chassis such as Escherichia coli and yeast. Current challenges in enzyme catalytic efficiency, host adaptability, and large-scale production are analyzed. Finally, the paper explores interdisciplinary directions such as AI-assisted rational enzyme design and dynamic regulatory network construction to advance the green and efficient biomanufacturing of baicalin.
As a traditional Chinese medicine, extracts of Tripterygium wilfordii Hook. f. have garnered significant attention for their anti-inflammatory, immunosuppressive, and antitumor activities. However, its undeniable “effect-toxicity homology” characteristic limits clinical application. Recent studies have revealed the multi-component synergistic mechanism of Tripterygium wilfordii’s active constituents, particularly how alkaloids and triterpenoids exert pharmacological effects by synergistically inhibiting signaling pathways such as NF-κB and JAK/STAT. Concurrently, breakthroughs have been achieved in elucidating its toxic mechanisms. Building upon these mechanisms, researchers have employed scientific approaches such as structural modification and novel delivery systems to significantly reduce toxicity while preserving pharmacological activity. Furthermore, biotechnological methods including gene editing and synthetic biology offer novel avenues for toxicity reduction at its metabolic source. Based on recent studies of the chemical composition, pharmacological effects, toxicological mechanisms, and detoxification strategies of Tripterygium wilfordii extracts, this review systematically reviews innovative drug development strategies for this herb, aiming to provide a theoretical basis for developing Tripterygium drugs with higher efficacy and lower toxicity.
Food-medicine homology active peptides refer to small-molecule peptide compounds derived from protein-containing materials that possess both food properties and medicinal value. These peptides are released through processes such as enzymatic hydrolysis, fermentation, or gastrointestinal digestion. They possess specific amino acid sequences and lengths, enabling them to exert beneficial physiological regulatory effects on the health of the human body. Owing to their characteristics of high bioactivity, low toxicity, and ease of absorption, these peptides have become a research hotspot in the fields of chronic disease prevention and treatment as well as health promotion. However, how to efficiently screen and prepare, and clarify their mechanisms of action remains urgent problems to be solved. This paper focuses on reviewing the physiological functions, structure-activity relationships, efficient mining, separation and purification, and preparation methods of food-medicine homology active peptides, with an emphasis on discussing their potential in the development of functional foods and preventive drugs. The aim of this review is to promote the efficient exploitation of bioactive peptides from food-medicine homology resources, facilitate the integration of functional foods and biomedicine, and contribute to the development of China’s big health industry.
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic non-specific inflammatory bowel disease. The pathogenesis of IBD involves genetic, environmental, microbial, immune, and other factors. In recent years, it has been found that macrophages are a major participant in intestinal immune homeostasis and IBD development, and can be polarized to a pro-inflammatory phenotype M1 or anti-inflammatory phenotype M2 under the stimulation of different microenvironments. Macrophage M1/M2 polarization is regulated by a variety of signaling pathways, and an imbalance in polarization is an important factor affecting the regression of IBD. Traditional Chinese medicine (TCM) has a long history of treating IBD, and has the advantages of fewer side effects and lower price compared with Western treatments such as 5-aminosalicylic acid, glucocorticoids, and immunosuppressants. Numerous studies have found that TCM can treat IBD by intervening in signaling pathways to re-establish the homeostasis of macrophage polarization and inhibit intestinal inflammatory responses. Therefore, this paper conducts a systematic review of the relationship between the regulation of macrophage polarization by relevant signaling pathways and the occurrence and development of IBD, as well as the research progress of TCM in regulating macrophage polarization through intervention of signaling pathways for the treatment of IBD, with the aim of providing new ideas and references for the prevention and treatment of IBD by TCM.
Objective: This study aims to investigate how Babao Dan (BBD) affects colorectal cancer-related macrophage polarization, gut microbiota, and their associated metabolites. Methods: A mouse transplant tumor model was established in BALB/c mice via subcutaneous injection of CT26 colorectal cancer cells. The experiment included three groups: Control group (Control), Model group (Model), and BBD group (BBD). The body weight of mice, volume of tumors, and weight of tumor masses were measured. Immunohistochemistry was used to detect Ki-67 expression in subcutaneous transplant tumor tissues, and to analyze the polarization of macrophages (F4/80, CD68), M1-type macrophages (CD86, CD11c), and M2-type macrophages (Arg-1, CD206). 16S rRNA sequencing and non-targeted metabolomics sequencing were employed to analyze gut microbiota and differential metabolites, and to investigate the correlation between microbiota and metabolites. Results: BBD was found to inhibit the growth of colorectal cancer subcutaneous transplant tumors, reduce the expression rate of Ki-67 in tumor tissues, increase the number of macrophages, promote the polarization of M1-type macrophages, and suppress the polarization of M2-type macrophages. BBD was found to reduce the abundance of Firmicutes while increasing the abundance of Bacteroidetes, along with a significant decrease in the Firmicutes/Bacteroidetes ratio (P< 0.05). When screening for differential metabolites using variable imoportance in projection value and fold change criteria, prostaglandin E2 was identified as being associated with macrophage polarization. From the analysis of the correlation between the differential flora and differential metabolites, it was found that prostaglandin E2 was significantly positively correlated with the genus Candidatus Arthromitus (P< 0.01). Conclusion: BBD can promote the polarization of M1-type macrophages, inhibit the polarization of M2-type macrophages, improve the distribution of gut microbiota, and affect the metabolism of prostaglandin E2 in the intestine, thereby playing a role in inhibiting the growth of subcutaneous transplant tumors in colorectal cancer mice.
Objective: Based on our previous confirmation that Kuding tea extract (Ligustrum robustum Blume extract, LRE) ameliorates high-fat diet (HFD)-induced microbial dysbiosis and metabolic syndrome, its in-depth mechanism remains unclear. This study aimed to investigate whether LRE alleviates HFD-induced obesity by regulating bile acid (BA) metabolism and related signaling pathways. Methods: A mouse model of HFD-induced obesity was established and orally administered LRE (200 mg·kg-1·d-1) for 16 weeks. Changes in body weight, white adipose tissue (WAT) weight, and adipocyte morphology were detected. Targeted metabolomics was used to analyze changes in BA profiles in feces and bile. The mRNA and protein expression levels of key molecules in BA metabolism-related signaling pathways (such as FXR, FGF15, FGFR4, CYP7A1, AMPK) in liver and colon tissues were detected by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot. Results: LRE intervention significantly reduced body weight gain, WAT weight, and adipocyte hypertrophy in HFD-fed mice. LRE markedly altered the BA profiles in feces and bile, increasing the levels of ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA). Further mechanistic studies showed that LRE suppressed the activation of intestinal farnesoid X receptor (FXR) and blocked the subsequent enterohepatic FGF15/FGFR4 signaling pathway. Concurrently, LRE activated the hepatic AMPK signaling pathway, thereby reducing the expression of lipogenesis-associated factors. Conclusion: LRE likely improves HFD-induced obesity, adipose tissue inflammation, and lipid metabolism disorder by promoting UDCA production and modulating bile acid signaling pathways, specifically by inhibiting the intestinal FXR/FGF15/FGFR4 pathway and activating the hepatic AMPK pathway. This study provides experimental support for the clinical application of LRE.
Objective: Danlong Dingchuan Decoction is an empirical formula derived from Jinshui Liujun Decoction by modification. Clinical practice has demonstrated its significant alleviating effect on asthma. This study aims to evaluate the improvement effects of Danlong Dingchuan Decoction on asthmatic inflammation and to explore its mechanisms using transcriptomics. Methods: Sixty SPF-grade female BALB/c mice were randomly divided into six groups (10 mice per group): normal control group, model control group, dexamethasone 0.63 mg/kg group, Danlong Dingchuan Decoction 13.28 g/kg group, Danlong Dingchuan Decoction 26.56 g/kg group, and another Danlong Dingchuan Decoction 53.12 g/kg group (note: potential duplication in grouping, please verify). Except for the normal control group, mice in other groups were sensitized by intraperitoneal injection of 0.2 mL OVA solution on days 1 and 14. On day 28, they were challenged with ultrasonic nebulization of 1% OVA saline solution at maximum fog volume, 30 minutes daily for 5 consecutive days. From day 35, asthma was induced by nebulizing 1% OVA solution 3 times weekly, while each drug group received daily intragastric administration for 6 weeks. One hour after the last administration, airway responsiveness was evaluated. Pulmonary pathological changes were assessed using hematoxylin-eosin (H&E) staining and Masson staining. Transcriptomics was employed to identify potential therapeutic targets of Danlong Dingchuan Decoction for asthma, followed by enrichment analysis and experimental validation. Results: Compared with the normal group, the model group showed significantly increased Penh values after methacholine stimulation at different concentrations, obvious peribronchial inflammatory infiltration and collagen deposition, and significantly increased serum levels of IL-17 and TGF-β, while IL-10 levels were significantly decreased. Compared with the model group, Danlong Dingchuan Decoction significantly reduced Penh values, improved peribronchial inflammatory infiltration and collagen deposition, decreased serum IL-17 and TGF-β levels, and increased IL-10 levels (P< 0.05 or P< 0.01). RNA-seq analysis revealed that the IL-17 signaling pathway might be the main mechanism by which Danlong Dingchuan Decoction improves asthmatic inflammation. This study confirmed that Danlong Dingchuan Decoction significantly regulates the mRNA and protein expression of the TRAF3IP2/TRAF6/IL-17RA/IL-17A pathway in lung tissue.Conclusion: The improvement of asthmatic inflammation by Danlong Dingchuan Decoction may be related to its inhibition of the TRAF3IP2/TRAF6/IL-17RA/IL-17A pathway.
Objective: Based on high-resolution mass spectrometry, the global natural product social molecular networking (GNPS) platform, and network pharmacology, this study aimed to systematically analyze the material basis of the ethyl acetate extract of Lysimachiae Herba in the treatment of cholestatic liver injury. Methods: Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was used an for untargeted MS/MS analysis of the ethyl acetate fraction of Lysimachiae Herba. A molecular network was constructed on the GNPS platform based on the acquired mass spectrometry data. By integrating information on precise mass, retention time, fragment ions, and mass spectral fragmentation patterns, the chemical constituents in the ethyl acetate extract of Lysimachiae Herba were rapidly identified. Furthermore, network pharmacology was applied to explore the potential effective substances and mechanisms underlying the therapeutic effects of the ethyl acetate extract on cholestatic liver injury. Results: A total of 46 chemical constituents were rapidly characterized from the ethyl acetate extract of Lysimachiae Herba via GNPS, including 13 flavonoids, 15 phenolic acids, 1 terpenoid, 1 coumarin, and 16 other compounds, among which 2 constituents were identified from Lysimachiae Herba for the first time. Seven potential active components for treating cholestatic liver injury were screened, including epicatechin gallate, (+)-epicatechin gallate, caffeic acid, phenylethyl caffeate, (+)-catechin, kaempferol, and 5,6,2’-trimethoxyflavone, along with 10 potential targets. Conclusion: The application of GNPS enables efficient analysis and identification of the chemical constituents in the ethyl acetate extract of Lysimachiae Herba. Furthermore, its combination with network pharmacology can rapidly reveal the material basis of its therapeutic effect on cholestatic liver injury.
Traditional Chinese medicine (TCM) is characterized by its multi-component and multi-target approach in preventing and treating diseases. Therefore, efficient and accurate screening of the active components of TCM is crucial for establishing a scientific basis for its efficacy. Traditional screening methods, which mainly rely on phenotypic screening experiments are limited by low efficiency methodologies and long cycle times. In light of these limitations, the emergence of artificial intelligence has provided an exciting and technically advanced method for the rapid discovery of active components in TCM. It is evident from previous studies that machine learning-based screening models can significantly improve the efficiency and accuracy in screening for active components in TCM. By integrating structural features of TCM compounds, target annotation data, and disease-related molecular networks, machine learning models enable the construction of efficient drug screening systems capable of rapid activity prediction and compound prioritization. This review summarizes the literature on the construction and application of machine learning models in TCM active compound screening and explores their efficiency in compound activity prediction and mechanism elucidation. This work aims to provide theoretical insights and methodological guidance for advancing intelligent systems-based drug screening of TCM and promote innovative drug discovery.
Research on the material basis of Traditional Chinese Medicine (TCM) is a key step to clarify the modern scientific connotation of its traditional efficacy. This paper systematically reviews the paradigm shift in this field, which has evolved from the early focus on screening single active components to the gradual emphasis on multi-component synergy and holistic pharmacodynamic analysis. It highlights the important role of emerging technologies such as chemomics, network pharmacology, metabolomics, and gut microbiome in promoting the transformation of TCM research from “reductionism” to “holism”. Furthermore, this paper proposes an integrative concept of “TCM intestinal transformation metabolomics”, emphasizing the core role of gut microbiota in the biotransformation of TCM components and the exertion of their pharmacological effects. Finally, the future directions of multi-omics integration and artificial intelligence in elucidating the systematic mechanism of TCM action, promoting precision medication, and improving quality evaluation are prospected, aiming to provide theoretical support and methodological reference for the in-depth development of TCM modernization and internationalization.
