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.

Illustrated Classics of Materia Medica, compiled under the direction of Su Song in the Northern Song Dynasty, is a milestone work in pharmaceutical literature, pioneering a new paradigm of “one drug, one illustration; mutual verification between text and image” for materia medica compilation. This study presents the first systematic collation and thematic analysis of the marine traditional Chinese medicines (TCMs) documented therein. Employing philological methods and based on a narrow definition of marine TCMs, the research identifies 44 marine TCMs recorded in the Illustrated Classics of Materia Medica. Analysis reveals that these drugs are primarily distributed across the sections of insects & fish, herbs, and minerals & stones, with animal-derived medicines, particularly mollusks, constituting the majority. Their medicinal properties exhibit the core pattern of being “salty and cold in nature, predominantly attributing to the liver and kidney meridians.” Their efficacies are concentrated in three major categories: clearing heat, resolving phlegm and relieving cough and asthma, and tonifying and replenishing. The theoretical framework of the properties of Marine TCM has been initially constructed. The study elucidates the pivotal role of the Illustrated Classics of Materia Medica in bridging past and future in the historical development of marine TCMs: compared to the Newly Revised Materia Medica, it added 14 new marine medicines such as razor clam, carapax eretmochelydis, mussel, and laid the documentary foundation for the integrative development seen in the Classified Materia Medica. Its academic contributions are mainly manifested in providing a basis for morphological textual research through its printed illustrations, deepening the understanding of medicines via detailed descriptions and rigorous error correction, and advancing marine TCMs from mere knowledge documentation towards quality control and clinical application by discussing authenticity and quality, integrating formulas with medicines, and emphasizing geo-authenticity. This paper systematically expounds the Illustrated Classics of Materia Medica’ outstanding contributions to the variety collation, knowledge system construction, and early application practices of marine TCMs, providing historical reference and academic support for the contemporary resource verification, quality evaluation, and innovative development of marine TCMs.

Objective To explore the therapeutic effect of Pteria martensii meat extract (PMME) on aplastic anemia (AA) rats and characterize its components entering the blood. Methods An AA rat model was established by combined administration of cyclophosphamide and acetylphenylhydrazine. After drug intervention, the effects of PMME on peripheral blood cells, bone marrow nucleated cells, bone marrow morphological changes, levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), erythropoietin (EPO) in serum and levels of vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1) in bone marrow suspension of AA rats were investigated. Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was employed for the qualitative analysis of PMME, and the differences in components entering the blood between normal rats and AA rats after ig PMME were compared. Results Compared with model group, the numbers of red blood cells, white blood cells and hemoglobin level in peripheral blood of rats in PMME group were significantly increased (P < 0.01), the number of platelets was significantly decreased (P < 0.05, 0.01), the levels of TNF-α, IFN-γ and EPO in serum were significantly decreased (P < 0.05, 0.01), the levels of VEGF-A and VCAM-1 in bone marrow suspension were significantly increased (P < 0.05), the number of nucleated cells in bone marrow significantly was increased (P < 0.05, 0.01), and the degree of bone marrow destruction in rats was significantly reduced. A total of 69 components including amino acids, nucleosides, organic acids, vitamins, purines and sterols were identified from PMME, with the main chemical components being organic acids, amino acids, and nucleosides. Four components, namely valine, eicosaenoic acid, histidine, and arachidonic acid, were identified in the drug containing plasma of normal rats, while seven components, namely phenylalanine, eicosaenoic acid, tyrosine, sebacic acid, linoleic acid, palmitic acid, and isoleucine, were identified in the drug containing plasma of AA rats. Conclusion PMME has a significant therapeutic effect on AA rats and can improve various indicators and bone marrow damage in AA rats. The main components of PMME are organic acids, amino acids, and nucleosides, with eicosaenoic acid and histidine entering the bloodstream in the form of prototype components or metabolites, which can serve as the pharmacological substance basis for treating AA rats.

Objective To optimize the extraction process of Huashi Zhitong Formula (化湿止痛方) and preparation technology of its gel formulation, elucidate the therapeutic efficacy and mechanism of Huashi Zhitong Gel against gouty arthritis, and provide a candidate formulation and theoretical basis for the development of new topical drugs for gouty arthritis. Methods The total phenolic acid content in Huashi Zhitong Formula was determined by ultraviolet spectrophotometry. The extraction process was optimized through single-factor and orthogonal tests. The gel matrix and excipient ratios were screened based on appearance, viscosity, ductility and stability, and the preparation process was further optimized using Box-Behnken response surface methodology. A rat gouty arthritis model was established, anti-gouty arthritis efficacy of Huashi Zhitong Gel was investigated by detecting joint swelling, skin temperature, pain and expressions of inflammatory factors [interleukin-1β (IL-1β), macrophage inflammatory protein-1α (MIP-1α), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), matrix metalloproteinase 9 (MMP9)]. Integrated with GEO data, network pharmacology and molecular docking, a “component-effect group” network was constructed to analyze the mechanism of Huashi Zhitong Gel against gouty arthritis, followed by experimental validation. Results The optimal extraction conditions of Huashi Zhitong Formula were determined as 60% ethanol, a solid-to-liquid ratio of 1∶10, extraction at 70 ℃ for 1.5 h (repeated twice). The optimal gel formulation consisted of 1% carbomer 940 and 0.2% poloxamer 188 as the matrix, combined with 7.5% humectant, 1.2% penetration enhancer, 14.7% drug load and 0.07% antioxidant. Pharmacodynamic experiment results demonstrated that Huashi Zhitong Gel significantly alleviated joint swelling and pain in rats with gouty arthritis (P < 0.01, 0.001), reduced the levels of IL-1β, MIP-1α in serum and expressions of TLR4, MMP9 in synovial tissue (P < 0.05, 0.01), and increased the activity of SOD in serum (P < 0.05, 0.01). The mechanism study showed that Huashi Zhitong Gel could play an anti-gouty arthritis role by regulating the targets such as prostaglandin endoperoxide synthase 2 (PTGS2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), and the pathways such as cyclic adenosine monophosphate (cAMP), chemokines, and calcium signaling. Immunofluorescence staining and qRT-PCR confirmed that Huashi Zhitong Gel could significantly inhibit the expressions of cyclooxygenase-2 (COX-2), VEGFA and EGFR in synovium of rats with gouty arthritis (P < 0.01). Conclusion The extraction and preparation process of Huashi Zhitong Gel are successfully optimized. Huashi Zhitong Gel has a good anti-gouty arthritis effect, and its mechanism is related to multi target and multi pathway regulation.

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..

Objective To establish an HPLC fingerprint profile and multi-indicator component quantification method for Pteria fucata (PF), and systematically evaluate the effects of different processing methods by combining chemometrics and electronic nose technology, and quality states on its main chemical components and odor characteristics. Additionally, correlation analysis was conducted to reveal the relationships between chemical markers and electronic nose responses, enabling a multidimensional comprehensive evaluation of PF quality. Methods HPLC was used to establish the chemical fingerprint profile of PF, and the contents of glutamic acid, glycine, taurine, and alanine were quantitatively determined. Chemometric methods, including cluster analysis (CA) and principal component analysis (PCA), were applied to evaluate chemical differences among different samples. An electronic nose was employed to capture olfactory information, and Pearson correlation analysis was used to construct a model linking chemical components with odor responses. Differences among samples processed by various methods and quality states were systematically compared. Results An HPLC fingerprint profile of PF was established, identifying four common peaks corresponding to taurine, glutamic acid, glycine, and alanine. Peaks 1, 9, 11, and 12 could distinguish between fresh PF microwave (XW) and spoiled PF microwave (FW) processing methods. The similarity of chemical fingerprints among 48 samples with different processing methods and quality states ranged from 0.793 to 1.000. The established fingerprint method demonstrated good specificity and could differentiate samples of varying quality and processing methods, providing a reliable tool for quality control and evaluation. CA and PCA results indicated certain differences among PF samples of varying quality and processing methods. Quantitative analysis showed that the fresh PF drying (XH) process best preserved multiple indicator components. Electronic nose detection effectively distinguished samples of different quality and processing methods. Correlation analysis revealed that glutamic acid was significantly positively correlated (P < 0.05) with electronic nose channels 1, 2, and 4, which are sensitive to alkanes and organic volatile compounds, indicating its potential as a core feature component linked to electronic nose responses. Conclusion This study is the first to combine HPLC fingerprinting, multi-indicator component quantification, and electronic nose technology to establish a stable and reliable comprehensive quality evaluation system for PF. The method exhibits good repeatability and discriminative ability, enabling effective assessment of PF quality in terms of chemical composition and volatile odor characteristics, particularly distinguishing fresh from spoiled states. The fresh PF drying (XH) process maximizes the retention of key amino acids such as glutamic acid while maintaining odor stability, making it a superior processing method balancing component preservation and quality control.

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 establish X-ray diffraction (XRD) fingerprint profiles of Crassostrea hongkongensis and determine its calcium carbonate content. Methods A total of 16 batches of C. hongkongensis samples were analyzed by XRD to establish the fingerprint. Based on hierarchical clustering analysis (HCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), characteristic information for identification of Crassostrea Hongkongensis concha was screened with variable importance in projection (VIP) value > 1. The content of calcium carbonate in the samples was determined by EDTA complexometric titration. Results The XRD fingerprint of C. hongkongensis was established, and its phase structure belongs to calcite-type calcium carbonate, with 13 common peaks identified. The similarity of all 16 batches of samples was greater than 0.99. HCA divided the 16 batches into 3 categories, and the VIP values of OPLS-DA showed that 5 diffraction angles made great contributions, which were 47.41°, 65.51°, 61.28°, 47.04° and 57.34° respectively. Among the 16 batches of samples, 15 batches had a calcium carbonate content exceeding 94%. Conclusion The established XRD fingerprint can be used for the identification and analysis of C. hongkongensis. Their quality meets the standards specified under Ostreae Concha recorded in the Pharmacopoeia of the People’s Republic of China (2025 edition), offering technical support for their development as traditional Chinese medicinal material and comprehensive utilization.

Objective To systematically investigate the chemical constituents of 70% acetone extract of Polygonatum cyrtonema processed by nine cycles of steaming and sun-drying. Method Compounds were isolated and purified by MCI gel, silica gel, Toyopearl HW-40C, ODS and semi-preparative HPLC. Their chemical structures were comprehensively elucidated by spectroscopic methods, such as HRESIMS, NMR, IR, UV and ECD. Results A total of 14 nitrogen-containing compounds were finally isolated and identified as 6-[(8R,9S)-8,9,10-trihydroxybutyl]-3,4-dimethylpyridazine (1), 6-ethyl-3-(hydroxymethyl)-1H-pyridin-2-one (2), (+)-(1R,3R)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (3), 1H-indole-3-carboxaldehyde (4), cyclo-(L-Leu-L-Phe) (5), cyclo-(L-Phe-L-Ile) (6), cyclo-(L-Asn-L-Phe) (7), (3S,6S)-3-benzyl-6-(1-hydroxyethyl)-2,5-piperazinedione (8), cyclo-(D-Phe-Gly) (9), cyclo-(L-Tyr-L-Tyr) (10), cyclo-(L-Val-L-Tyr) (11), pedatisectine L (12), cyclo-(Ala-Tyr) (13), and (2S,5S)-5-[(1S)-1-methylpropyl]-3,6-dioxo-2-piperazinepropanoic acid (14). Conclusion Compounds 1 and 2 were characterized as two new compounds named cyrtoneine J and cyrtoneine K, while compounds 3 and 5—14 were isolated from the genus Polygonatum for the first time.