Objective To establish a rapid and intelligent analytical method for evaluating the quality and grade of the marine traditional Chinese medicinal material Madao, from Guangxi, based on its potential pharmacodynamic components. Methods The contents of calcium carbonate, acid-insoluble ash, and extractives in Madao were determined following the methods specified for oysters in the Chinese Pharmacopeia (2025 edition). The total amino acid content was measured using the ninhydrin method. A multi-task one-dimensional convolutional neural network (1D-CNN) model was constructed, using near-infrared spectroscopy (NIRS) data as input to simultaneously predict the contents of multiple components. A spectral attention mechanism was introduced to enhance model interpretability. Furthermore, the criteria importance through intercriteria correlation (CRITIC) objective weighting method and the technique for order preference by similarity to ideal solution (TOPSIS) multi criteria decision making algorithm were integrated to develop an end-to-end AI-NIRS intelligent evaluation platform. This platform enables automatic classification of quality grade based on comprehensive scores. Results A score-grade prediction model was established based on the determination results of 90 batches of Madao samples using the 1D-CNN. Compared with the traditional partial least squares (PLS) NIRS model, the multi-task CNN model demonstrated significantly superior performance. Validation results showed that the comprehensive scores of the Madao samples followed a Gaussian distribution, with clear differentiation among the various quality grades. This indicates that the established evaluation method is effective and reliable. Conclusion Operating within the framework of the current regulatory system, this method achieved rapid, comprehensive quality assessment and grade differentiation for Madao. It provides a novel technological approach for the digital-intelligence evaluation and scientific supervision of shell-based marine traditional Chinese medicinal materials.

Objective To identify novel glycosaminoglycans from Linckia laevigata, elucidate their fine structures, and evaluate their anticoagulant potential as inhibitors of the intrinsic coagulation pathway. Methods Total polysaccharides were extracted from the starfish L. laevigata using a combination of enzymatic and alkaline hydrolysis, and then purified by strong anion-exchange chromatography. Oligosaccharides were prepared through deacetylation-deamination depolymerization. A “bottom-up” strategy integrating high-performance gel permeation chromatography (HPGPC), 1-phenyl-3-methyl-5-pyrazolone derivatization high-performance liquid chromatography (PMP-HPLC), infrared spectroscopy (IR), and one-dimensional/two-dimensional nuclear magnetic resonance (1D/2D NMR) was employed for structural characterization. In vitro anticoagulant activity was assessed by activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) assays, while inhibition of intrinsic factor Xase (iFXase) was measured via a chromogenic substrate assay. Results A homogeneous sulfated glycosaminoglycan, designated LLGAG (molecular weight, M_w≈38 000), was obtained with a monosaccharide composition of iduronic acid (IdoA)∶N-acetylgalactosamine (GalNAc)∶galactose (Gal) ≈34.4∶59.7∶5.9. The polymer core comprised disaccharide units featuring the L-IdoA_2S3S-α-1,3-D-GalNAc_4S6S (2S3S4S6S) motif, together with 3S4S6S and 2S3S6S motifs, representing a rare and novel dermatan sulfate-like glycosaminoglycan. In vitro, LLGAG significantly prolonged APTT and TT, showing activity comparable to that of the clinical gold-standard enoxaparin sodium. Its half-maximal inhibitory concentration (IC₅₀) for iFXase inhibition was (17.75 ± 1.12) ng/mL, approximately 2.8-fold more potent than that of enoxaparin sodium. Conclusion This study identified a structurally unique glycosaminoglycan from L. laevigata, elucidated its precise structure, and demonstrated its potent iFXase inhibitory activity, thus providing both a theoretical foundation and a candidate molecule for the development of marine-derived heparin alternatives.

Objective To systematically identify potential angiotensin-converting enzyme (ACE) inhibitory peptides from proteins in waste pearl shells of Pteria martensii using an integrated in silico and experimental (“dry-wet”) strategy. Methods Waste pearl shells were subjected to decalcification and dialysis to obtain nacre proteins. The optimal protease was screened using ACE inhibitory activity and degree of hydrolysis as evaluation indicators. The enzymatic hydrolysates were separated and purified via ultrafiltration and gel filtration chromatography, and the peptide sequences of active fractions were characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatic tools were applied to predict and screen peptides with high potential ACE-inhibitory activity; candidate peptides were then prepared by solid-phase peptide synthesis (SPPS) and verified for their in vitro ACE inhibitory capacity. Lineweaver-Burk double-reciprocal plots were used to calculate enzyme kinetic parameters and define the inhibition mode of active peptides. An in vitro simulated gastrointestinal digestion assay was performed to evaluate the digestive stability of target peptides. Molecular docking was performed to investigate the interactions between the active peptide and ACE and to compare its interactions with the active sites in the N- and C-domains of ACE. Molecular dynamics (MD) simulations were conducted to assess the conformational stability and dynamic interaction characteristics of peptide-ACE complexes. Results Eight proteases were used to hydrolyze nacre proteins, among which papain hydrolysate showed a degree of hydrolysis of (11.77 ± 0.09)% and a half-maximal inhibitory concentration (IC₅₀) of (2.03 ± 0.14) μg/mL against ACE. After separation and purification, the active fraction F1 was harvested with an IC₅₀ value of (1.56 ± 0.06) μg/mL. A total of 294 unique peptides were identified from F1, and nine peptides with high predicted activity were selected for solid-phase synthesis and in vitro activity validation. Among all synthetic peptides, peptide SPAR exhibited the strongest ACE inhibitory activity with an IC₅₀ of (33.46 ± 0.56) μmol/L, and its inhibitory pattern against ACE was confirmed as mixed-type inhibition. After in vitro simulated gastrointestinal digestion, the retention rate of SPAR was (23.6 ± 4.9) %. Molecular docking results revealed that SPAR formed hydrogen bonds with key amino acid residues located in the S1 and S2 active pockets of ACE, including Ala354, Glu384, Tyr523, Gln281 and Lys511. SPAR was capable of binding to both the N-domain and C-domain of ACE, and displayed stronger binding affinity for the C-domain. MD simulation results demonstrated that the SPAR-ACE complex maintained favorable conformational stability and sustained intermolecular interactions throughout the simulation period. Conclusions Eight novel ACE inhibitory peptides were successfully screened from waste pearl shell proteins via the integrated dry-wet strategy, among which peptide SPAR possessed the optimal ACE inhibitory activity. This work provides a novel research perspective and technical route for high-value reutilization of discarded pearl shells. The complementary combination of in silico prediction and wet-lab experiments enables more efficient excavation of latent bioactive peptides from traditional Chinese medicine waste proteins..

Marine traditional Chinese medicine (MTCM), as an important component of the traditional Chinese medicine system, has long been utilized for disease prevention, therapy, and health maintenance due to its unique biological origins and diverse pharmacological properties. China possesses abundant and distinctive marine biological resources, with more than 700 verifiable marine medicinal materials recorded in classical literature, including algae, shellfish, fish, and marine minerals, indicating substantial developmental potential. However, compared with terrestrial traditional Chinese medicines, the modernization of MTCM has started relatively late. Significant gaps remain in resource investigation, pharmacological interpretation, quality control systems, processing technologies, innovative product development, and industrial chain construction. Based on a systematic analysis, this review identifies four major scientific challenges currently hindering the development of MTCM: First, insufficient modern research and inadequate transformation of traditional knowledge. Second, low resource utilization efficiency, accompanied by ecological pressure and endangerment risks. Third, a predominant focus on chemical isolation with limited integration of traditional Chinese medical theory. Fourth, a shortage of high-level interdisciplinary talent and weak innovation systems. To address these bottlenecks, this study propose an integrated development framework spanning “resources-pharmacology-quality-processing-products-industry”. Key strategies include comprehensive resource surveys and database construction, integration of traditional medicinal theory with modern pharmacology, establishment of quality markers and safety evaluation systems, development of advanced processing and extraction technologies, and innovation in formulations and health products. Furthermore, phased development goals for MTCM are proposed. In the short term, priorities include resource investigation, standard system establishment, and efficacy evaluation. In the long term, efforts should focus on building a complete industrial chain and an internationalized research and development system to achieve large-scale industrialization and global expansion. Overall, MTCM holds significant promise under the “Healthy China 2030” initiative and within the global health industry. Through systematic planning and collaborative innovation, it is expected to advance toward systematization, modernization, and internationalization.

Objective To perform a visualized bibliometric analysis of research on the Dai medicine Clerodendranthus spicatus in the field of traditional Chinese medicine based on the CiteSpace knowledge graph, systematically summarize recent research trends, clarify hotspots and future directions, and provide a reference for further development and application of C. spicatus. Methods Chinese and English literature on C. spicatus in traditional Chinese medicine was retrieved from China National Knowledge Infrastructure (CNKI) and the Web of Science (WOS) Core Collection from 1 January 1995 to 30 October 2025. Records from each database were imported into NoteExpress for automatic and manual de-duplication, and then screened according to predefined inclusion and exclusion criteria. Based on the final dataset, CiteSpace and Microsoft Excel were used to perform visual analyses of publication output, authors, institutions, country distribution and keywords. In addition, the top 10 most-cited Chinese and English articles were subjected to high-cited literature analysis. Results A total of 626 publications were included, comprising 274 Chinese and 352 English articles, with an overall fluctuating upward trend in annual output. The most productive authors were Song Liqun and Ismail Zhari. Co-authorship networks showed relatively close collaboration within research teams but limited cooperation between different teams. The most productive institutions were the Yunnan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, and Universiti Sains Malaysia, with core institutions mainly being traditional Chinese medicine research institutes and universities. Malaysia was the most productive country. Keyword analysis indicated that Chinese studies mainly focused on medicinal resources, traditional uses and clinical research, whereas English literature emphasized phytochemical profiling, pharmacological activities, data mining and molecular mechanisms. High-cited literature analysis revealed that both Chinese and English classic studies chiefly concentrated on chemical constituents and material basis, pharmacological effects and mechanisms, preparation technology and modern methodological innovation, as well as research progress, collectively forming a “constituent-pharmacology-formulation” research framework. Conclusion Research on C. spicatus in the field of traditional Chinese medicine has shown sustained growth, with its pharmacological mechanisms and clinical applications in the prevention and treatment of kidney diseases, rheumatoid arthritis, gout, osteoarthritis, and cancer becoming major research hotspots. Future studies should integrate systems pharmacology and multi-omics technologies, strengthen mechanistic exploration, and establish scientific quality control and clinical evaluation systems, thereby promoting the modernization and innovative development of C. spicatus and providing a reference for research on this herb and other ethnic medicines.

Objective To elucidate the chemical composition differences among various parts of Pugongying (Taraxacum mongolicum), this study compared cultivated and wild T. mongolicum samples, dividing them into three parts: whole plant, above-ground parts, and roots. Methods A Venusil C₁₈chromatographic column was used with acetonitrile-0.2% phosphoric acid as the mobile phase for gradient elution at a flow rate of 1.0 mL/min, column temperature of 30 °C, and detection wavelength of 330 nm. A fingerprint spectrum of T. mongolicum medicinal materials was established, and the contents of six components (monocaffeoyl tartaric acid, chlorogenic acid, caffeic acid, ferulic acid, isochlorogenic acid C, and chicoric acid) were determined in different parts. The collected fingerprint spectrum data were analyzed using similarity evaluation, cluster analysis (CA), and orthogonal partial least squares discriminant analysis (OPLS-DA). Results The T. mongolicum fingerprint spectrum identified nine common peaks, with six major chemical components confirmed and five primary differential components screened. Quantitative analysis revealed significant differences in chemical composition content between T. mongolicum roots compared to whole plant and above-ground parts. Conclusion This method is simple, reliable, and highly reproducible. The comprehensive quality evaluation model provides objective analytical results suitable for holistic quality assessment of T. mongolicum medicinal materials. This study enriches research on quality analysis of T. mongolicum and offers evidence for future development, quality standardization, and clinical application.

Impaired exercise capacity is an independent risk factor for poor prognosis in patients with cardiovascular disease (CVD). The vicious cycle triggered by CVD, centered on cardiac dysfunction, progressively compromises pulmonary ventilation/gas exchange, skeletal muscle metabolism, and skeletal function, collectively leading to exercise intolerance. The “cardio-pulmonary-muscular-skeletal” functional axis theory is proposed to elucidate this multisystem deterioration. Within the framework, this review systematically discusses the mechanisms by which traditional Chinese medicine (TCM) interventions synergistically reverse exercise intolerance. These mechanisms include improving cardiac and vascular function, enhancing pulmonary ventilation and oxygenation, increasing muscle mass and metabolic function, and maintaining bone quality and mechanical function, thereby leveraging the multi-targeted and holistic regulatory advantages of TCM. Although the overall quality of clinical evidence remains moderate, a multidimensional evidence system centered on exercise tolerance has been established. This evidence confirms the consistent benefits of TCM formulas on core indicators across the functional axis. The functional axis theory provides an innovative framework for understanding the multisystemic underlying mechanisms of exercise capacity decline in CVD patients and for guiding holistic TCM-based interventions, highlighting the unique value of TCM in cardiac rehabilitation.

As the precursor of sex hormone synthesis, depression is profoundly influenced by metabolic pathways, which also affect how patients respond to antidepressants. In addition, when sex hormones are dysregulated, it significantly increases both the risk of developing depression and the likelihood of its worsening over time, and the disorder of cholesterol metabolism can lead to depression by disrupting the homeostasis of sex hormone microenvironment in the brain. Therefore, drugs can exert antidepressant effects by mediating cholesterol metabolism, regulating the levels of sex hormones and their receptors, and restoring the homeostasis of brain sex hormone microenvironment. This article aims to review the mechanism of the imbalance of brain sex hormone homeostasis caused by cholesterol mediated metabolic disorders of neurosteroid deficiency, hypothalamic-pituitary-adrenal axis hyperactivation, and inflammatory pathway activation. Furthermore, stable isotope tracing, metabolomics, biological network regulation and other technologies were applied to reveal the internal mechanism of “cholesterol metabolism sex hormone homeostasis depression”, as well as the regulatory effect of drug intervention on depression. It provides novel research strategies for revealing the mechanism of depression and drug intervention from the perspective of homeostatic regulation of sex hormone microenvironment.

Astragalus membranaceus, a traditional qi-tonifying herb, exhibits quality that is strongly influenced by ecological factors of the production region, cultivation practices, and processing techniques. Significant differences in morphology, chemical composition, and bioactivity are observed among different production areas: A. membranaceus from Hunyuan, Shanxi is characterized by high levels of calycosin-7-O-β-D-glucoside, that from Longxi, Gansu is enriched in astragaloside, while samples from Inner Mongolia contain higher concentrations of isoflavonoids. These variations arise from the intricate coupling between ecological factors (such as soil elemental composition, climate, and microbial communities) and genetic background, with associated plants and secondary metabolite regulatory networks serving as key mechanisms. Cultivation patterns exert considerable influence, as wild-simulated cultivation can approximate wild-type quality; appropriate planting density, water and nutrient management, and arbuscular mycorrhizal inoculation effectively enhance the accumulation of bioactive constituents. Harvesting and processing are equally critical: autumn harvest, hot air drying at 60 ℃, and honey-frying processing maximize retention of active compounds and improve immunomodulatory activity. Additionally, previous studies have examined chemical changes during processing and identified astragaloside and calycosin-7-O-β-D-glucoside as marker compounds, establishing quality control strategies from raw materials to final products. The 2025 edition of the Chinese Pharmacopoeia, which focus on single constituents, are insufficient to fully reflect the synergistic effects of constituent clusters. Expansion of cultivation areas exacerbates quality variability, and continuous cropping can disrupt soil microbial ecology. Future approaches should integrate multi-omics analyses and intelligent monitoring to develop a dynamic quality evaluation system based on bioactive constituents, and employ “soil–climate–genotype” matching models to optimize cultivation in non-authentic production regions, thereby promoting high-quality development of the A. membranaceus industry.

Objective This study aimed to investigate the correlation between bitterness and antioxidant activity in Coptis chinensis, systematically characterize its bitter-active compounds, and establish a corresponding quality control method, using an integration of electronic sensory techniques, UPLC-Q-TOF-MS/MS, and molecular docking. Methods The bitterness intensity and antioxidant capacity of C. chinensis. from three geographical origins were quantified via an electronic tongue and in vitro antioxidant assays, and a subsequent correlation analysis was conducted to explore their relationship. Chemical constituents were identified by UPLC-Q-TOF-MS/MS, and differential components and potential bitter compounds were screened by integrating plant metabolomics and correlation analysis between chemical components and bitterness. Molecular docking was performed to further screen components with strong binding affinity to the bitter taste receptors TAS2R1, TAS2R7, TAS2R8, and TAS2R14, and their binding modes were summarized. By integrating these results, the bitter-active compounds responsible for both taste and antioxidant effects were identified. Subsequently, a high-performance liquid chromatography (HPLC) method was developed for the simultaneous quantification of seven key bitter-active compounds (groenlandicine, jatrorrhizine, columbamine, epiberberine, coptisine, palmatine, and berberine) for quality control. Results Correlation analysis confirmed a positive relationship between bitterness intensity and antioxidant capacity across the three origins. UPLC-Q-TOF-MS/MS analysis led to the identification of 87 chemical constituents, from which origin-specific differential components and potential bitter-tasting substances were screened. Molecular docking identified 18 components with high binding affinity to the target bitter receptors, and their specific binding modes were elucidated. Integrated analysis pinpointed the bitter-active compounds in C. chinensis that contribute to both taste perception and antioxidant activity. A reliable HPLC method for the simultaneous quantification of the seven key bitter-active compounds was successfully established. Conclusion This study clarified the bitter-active compounds in C. chinensis and developed a quality control method based on these components. The findings provide a theoretical foundation and practical reference for elucidating the “bitter taste-efficacy” relationship and for optimizing the quality control system of C. chinensis.