Capsular polysaccharides and lipopolysaccharides are crucial bacterial virulence factors and key vaccine antigen targets. Over the past century, the development of bacterial polysaccharide-based vaccines has significantly advanced global efforts to prevent bacterial infections. This review outlines the historic milestones of bacterial polysaccharide vaccines, with an emphasis on the development and application of capsular polysaccharide-based vaccines against three human pathogens: Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Moreover, this article summarizes the protective mechanisms and perspectives of polysaccharide-based vaccines.

There exist significant changes in glycosyltransferase expression during tumorigenesis, which leads to the unique sugar chain structural characteristics of glycoproteins on the surface of tumor cells compared to normal cells, namely highly truncated sugar chains. These aberrant glycosylated products are called tumor-associated carbohydrate antigens (tumor-associated carbone antigens, TACAs). As an important molecular marker of malignant tumors, TACAs not only participate in the regulation of tumor occurrence, development, invasion and metastasis of tumors, but also play a key role in tumor immune escape. Thus, targeting abnormally glycosylated proteins or peptides on tumors have become one of most important anti-tumor drug development strategies. However, it is difficult to isolate glycoproteins from natural sources, and it is still challenging to synthesize complex glycoproteins or glycopeptides by chemical methods. This review summarizes the progress of glycopeptide anti-tumor vaccine synthesized by chemical methods in recent years, in order to provide theoretical basis and technical reference for the research and development of glycopeptide anti-tumor vaccine in the future.

Glycoconjugate vaccines are essential tools for preventing bacterial infectious diseases. Currently licensed glycoconjugate vaccines are produced through a stepwise process that involves the extraction of native polysaccharide antigens, purification of carrier proteins, and subsequent in vitro chemical conjugation. In recent years, the rapid advancement of emerging technologies such as synthetic biology has driven the development of innovative strategies for designing and manufacturing glycoconjugate vaccines. This review highlights progress in two representative technologies: protein glycan coupling technology (PGCT) and cell-free glycoprotein synthesis (CFGpS). It also briefly explores additional emerging approaches in glycoconjugate vaccine development, including generalized modules for membrane antigens (GMMA), semi-synthetic glycoconjugate vaccines, non-covalent coupling strategies, and click chemistry-based conjugation using non-natural amino acids. Looking ahead, advancements in artificial intelligence (AI) are expected to accelerate the computational design and engineering of oligosac-charyltransferases and carrier proteins, ultimately improving the immunogenicity and manufacturing efficiency of next-generation glycoconjugate vaccines.

Carbohydrate and glycopeptide vaccines have shown great promise in tumor prevention and treatment. However, their relatively low immunogenicity remains a significant challenge. To address this, adjuvants are commonly employed to enhance immune responses against specific antigens. Despite their widespread use, conventional adjuvants still face several limitations, including limited immune stimulation and potential safety concerns associated with molecular diffusion. A promising strategy to overcome these challenges is the incorporation of built-in adjuvants, which promotes adjuvants to augment their immunostimulatory effect. This review highlights the application of various immune agonists as built-in adjuvants to enhance vaccine immunogenicity, including Toll-like receptor (TLR) agonists, invariant natural killer T (iNKT) cell agonists, stimulator of interferon genes (STING) agonists, nucleotide-binding oligomerization domain-like receptors (NLR) agonists, and C-type lectin receptor (CLR) agonists. By summarizing recent advancements in this field, we provide valuable insights into the development of more effective and safer carbohydrate vaccines.

This study aims to evaluate the immunogenicity and safety of the 20-valent pneumococcal conjugate vaccine (PCV20). Different evaluation models were established using ICR mice and SD rats to assess the immunogenicity and toxic reactions. The results showed that the immunogenicity test in mice demonstrated good immunogenicity for three batches of the 20-valent pneumococcal conjugate vaccine after three doses. The immunogenicity test in rats showed that the vaccine induced antibodies against 20 pneumococcal serotypes within 2 weeks after the first dose and maintained a certain level for 3 weeks after the final dose, indicating good immune persistence. The vaccine was administered to mice at the maximum dosage without any significant toxic reactions observed. The repeated-dose safety test in rats showed local irritation and pathological changes at the injection site, which were alleviated during the recovery period. No significant toxic reactions were observed at the end of the dosing period and the recovery period. Studies have shown that the novel 20-valent pneumococcal conjugate vaccine exhibits good immunogenicity and safety in mouse and rat models. The use of all experimental animals has been approved by the Ethics Committee of Laboratory Animal of Beijing Minhai Biological Technology Co. Ltd. (No. 202309, 202311).

O-Antigens is the outermost component of bacterial lipopolysaccharide (LPS). Their structural complexity and diversity are essential for bacterial immune evasion, pathogenicity, and bacteria-host interactions. In this study, the O-antigen of lipopolysaccharide from Escherichia coli strain EPEC080 was extracted and purified. The chemical structure of the O-antigen was determined by a combination of various analytical methods, including molecular weight determination, monosaccharide composition analysis, infrared spectrum and nuclear magnetic resonance analysis. The O-antigen with an average molecular weight of 14.3 kDa was determined to consist of a pentasaccharide repeating unit: →4)-[α-D-GalpNAc-(1→3)]-α-L-Rhap-(1→2)-[β-D-GalpNAc-(1→3)]-α-L-Rhap-(1→2)-α-L-Rhap-(1→. Notably, this structure is different from those of known E. coli LPS O-antigens, indicating that strain EPEC080 represents a novel E. coli serotype. The structural identification of this O-antigen provides a foundation for further investigation of the pathogenesis of enteropathogenic E. coli and development of prophylaxis and treatment methods against the related diseases.

The serum bactericidal assay (SBA), a gold standard recommended by the World Health Organization for detecting antibody levels against Neisseria meningitidis (Nm), was utilized in this study. Based on the classic Nm bactericidal antibody detection methodology, we optimized experimental parameters including sample volume, complement selection, Nm target bacterial concentration, bactericidal reaction time, and positive reference serum concentration to establish a serogroup X Nm bactericidal antibody detection protocol. The specificity, repeatability, and stability of the positive reference serum were systematically validated. The established method was applied to analyze bactericidal antibody levels in 508 serum samples of healthy individuals under 5 years old from Hennan, Jiangsu, Anhui and Shanxi provinces. Geometric mean titers (GMT) were calculated and statistically analyzed by region and age group. Results demonstrated that 95.7% serum samples exhibited serogroup X Nm bactericidal antibody titers below 8, with an overall GMT of 2.20. No statistically significant regional differences in GMT were observed (H = 6.688, P = 0.083). Age-stratified analysis revealed that 6.37% of infants aged 0-11 months displayed antibody titers greater than or equal to 8. This proportion progressively declined with age, reaching 0.49% in the 2-5 years group. However, no significant inter-group differences in GMT were detected among age cohorts (H = 4.756, P = 0.093). The findings indicate that the serum bactericidal antibody titers against Neisseria meningitidis serogroup X (Nm X) are relatively low among healthy children under 5 years of age in China. This study has developed a reliable detection method for Nm X SBA with good specificity, stability, and reproducibility. Furthermore, it has provided the data on Nm X SBA levels among children under 5 years old from various regions, offering scientific guidance for the future prevention and control of serogroup X meningococcal disease in China. All the serum used in this experiment were approved by Henan Provincial Center for Disease Control and Prevention Ethics Review Committee (approval number: 2019YM-005-02), Jiangsu Provincial Center for Disease Control and Prevention Ethics Review Committee (approval number: JSJK202-A054-02), and Shanxi Provincial Center for Disease Control and Prevention Ethics Review Committee (approval number: SXCDCIRBP2020050001).

Cardiovascular complications triggered by stroke are known as stroke-heart syndrome (SHS). Emerging evidence indicates that stroke triggers dysfunction of the suprachiasmatic nucleus (SCN) through direct neural injury or indirect regulatory pathways, leading to disruption of the endogenous circadian rhythm system. This circadian disruption manifests as sleep-wake cycle dysregulation. It serves as a critical pathological driver of secondary cardio-cerebrovascular events via three interconnected mechanisms: rhythmic dysregulation of immune-inflammatory responses, destabilization of gut microbial homeostasis, and neuroendocrine hormonal imbalance. This paper innovatively proposed a cascade response of "stroke-circadian disturbance-heart syndrome", systematically elaborating on the circadian rhythm-targeted therapy strategy for SHS, including rhythm regulation of immune inflammatory pathways, synergistic regulation of gut microbiota circadian clock, and melatonin rhythm remodeling, as well as the potential of traditional Chinese medicine intervention, providing new perspectives and ideas for clinical prevention and treatment of SHS.

Ferroptosis, a form of non-apoptotic cell death, mainly depends on iron and reactive oxygen species (ROS) to trigger oxidative-reduction imbalance, causing membrane lipid peroxidation, cell membrane damage, and subsequent cell death. Recently, its crucial roles in embryonic development, metabolic regulation, neurodegenerative diseases, and cancer therapy have been unveiled. This article delves into the dynamic balance of cell membrane lipid peroxidation injury and repair mechanisms during ferroptosis, and dissects the multifaceted functions of mitochondria, lysosomes, etc., in regulating ferroptosis. The imbalance between membrane damage and repair is a hallmark of ferroptosis. The antioxidant system maintains membrane integrity by regulating lipid metabolism and redox homeostasis, while membrane repair mechanisms prevent cell death by removing lipid peroxides. Moreover, organelles interact dynamically through iron metabolism, ROS signaling, and lipid peroxide diffusion, modulating ferroptosis sensitivity. This article encapsulates the latest progress in ferroptosis mechanisms and highlights the potential of targeting membrane repair and organelle interactions for disease therapy, offering novel insights for precise disease intervention.

Silicosis is a progressive disease of the lungs triggered by inhalation of crystalline silica dust, characterized mainly by chronic lung inflammation and fibrosis with silicosis nodules. Epidemiological data show that the disease is highly prevalent in occupationally exposed populations, such as mining and building construction, and has become a major occupational health problem worldwide. The pathological process involves complex interactions between multiple cell types, including alveolar macrophages, epithelial cells and fibroblasts, with imbalances in the regulation of the adaptive immune system, particularly T lymphocytes, receiving much attention in recent years, and the mechanisms are not well understood. In this paper, we summarize the roles of CD4⁺ helper T cells and CD8⁺ cytotoxic T cells in silicosis, including the imbalance between different types of T cells (Th1/Th2/Th17/Treg subpopulations), the imbalance of cytokines secreted by the same type of T cells and the balance between their different cellular functions, which accelerate the development of silicosis, and the different specificity of this dynamic imbalance in different pathological stages. This dynamic imbalance presents different specificities at different pathological stages, and excessive immune disorders can lead to a variety of complications such as dyspnoea and autoimmune diseases. Therefore, maintaining the immune balance of pulmonary T-cells is essential for the prevention and treatment of silicosis. At the same time, clinical interventions are still limited to dust exposure control, glucocorticoid symptomatic treatment and end-stage lung transplantation, and there is a lack of specific therapies to address the pathogenic mechanisms. Novel therapeutic strategies based on T-cell subpopulation rebalancing have also shown potential value and may provide new therapeutic ideas for silicosis. Overall, this paper provides a systematic review of the dual regulatory mechanisms of T cells in silicosis and explores therapeutic perspectives for disease control through immune homeostasis reestablishment.

Cancer therapeutic drugs include traditional chemotherapy drugs, targeted therapy drugs, monoclonal antibodies, as well as novel antibody-drug conjugates (ADCs) and peptide-drug conjugates (PDCs). PDCs have demonstrated significant clinical advantages in cancer treatment, but they still face limitations such as poor stability and insufficient targeting specificity. In recent years, the application of multivalent targeting peptide strategies and dual targeting peptide strategies has significantly improved the targeting precision of PDCs. Meanwhile, molecular engineering approaches such as peptide cyclization, unnatural amino acid substitution, and fatty acid chain modification have effectively enhanced the in vivo stability of PDCs. These innovative strategies have markedly strengthened the pharmacological activity of PDCs and their therapeutic efficacy in tumors. Based on the structural characteristics and research progress of PDCs, this article systematically reviews the latest strategies for improving the targeting ability, stability, and cell membrane penetration efficiency of PDCs, aiming to provide a theoretical foundation and research insights for the development of PDC-based anticancer drugs with superior pharmacodynamic properties.

Polypyridine derivatives represent a significant class of ligands in coordination chemistry, renowned for their stable coordination capabilities and low toxicity to biological systems, making them ideal candidates for constructing anticancer complexes. Their metal complexes exhibit potential anticancer activity against various malignancies, including breast cancer, prostate cancer, myeloid leukemia, and pancreatic cancer. The iron group elements (iron, cobalt, nickel) have garnered extensive attention from researchers due to their unique redox activities and biochemical properties. To address the issue of drug resistance in existing anticancer therapies, researchers have begun exploring the application of iron group elements in the field of anticancer research. Through extensive structural modifications of polypyridine ligands, a series of metal complexes with novel structures and excellent biological activities have been successfully synthesized. This article reviews the synthesis, cytotoxicity, mechanisms of action, and application potential of polypyridine-based iron group metal complexes over the past decade, providing a theoretical foundation and innovative insights for the development of new anticancer drugs.

At present, all known marine-derived 1,6-naphthyridine natural products have been isolated from sponge organisms. Research indicates that these compounds exhibit significant biological activities in various fields, including antitumor, antioxidant, and antibacterial properties, demonstrating broad potential for drug development. This article systematically reviews the sources, chemical structures, biological activities, and mechanisms of action of 42 marine-derived 1,6-naphthyridine natural products. This study aims to systematically summarize the biological activities of these natural products, thereby identifying novel structures and prominent active compounds as potential leads for new drug development. At the same time, these studies lay the foundation for the development of highly effective and low-toxicity new drugs, thereby making an important contribution to human health.

Polysaccharides from marine organisms are an important source for researching and developing innovative carbohydrate-based drugs. Echinoderms, such as sea cucumber, starfish, sea urchin, and brittle star, are rich in resources. The polysaccharides from these species exhibit unique structural features and possess extensive, potent pharmacological activities, making them promising lead compounds for carbohydrate drug development. In recent years, significant progress has been made in the isolation and purification, structural analysis, and activity evaluation of marine echinoderm polysaccharides. Notably, the fine structures of several polysaccharides have been elucidated, and several novel polysaccharides with nanomolar-level activity have been identified. However, numerous challenges and deficiencies remain in the research areas related to structural elucidation, structure-activity relationships, and mechanisms of action. This review systematically summarizes the progress and breakthroughs in the study of marine echinoderm polysaccharides and provides new insights and suggestions, which may offer important reference information for the research and development of low-toxicity, high-efficiency marine carbohydrate drugs, thereby advancing the field of marine-derived pharmaceuticals.

With the rapid development of artificial intelligence technology, the application of large language model (LLM) in the field of biomedical and clinical applications has gradually deepened. Drug-drug interaction (DDI) prediction is a kind of safety study with complex characteristics in drug development and use, and traditional methods rely on experimental validation or rule-based computational models, which are time-consuming and lagging in updating. Big language models provide a new paradigm for drug interaction prediction through semantic modeling and integrating knowledge-based reasoning on polymorphic data. In this paper, we systematically review the technical progress, application cases and technical difficulties of deep learning and big language modeling in DDI prediction. Based on the performance of five mainstream big language models, namely ChatGPT-4, DouBao, ERNIE Bot, Kimi Chat, and DeepSeek-R1, in the verifiable drug combination DDI analysis task, we explore the value of the application of big language models in drug interaction prediction and provide an outlook on the future development trend, and system development, individualized prediction optimization, and standardized system development, individualized prediction optimization, and the construction of a standardized DDI prediction framework, with a view to promoting the translation process of LLM from the laboratory to the clinic.

Traditional chemotherapy methods lack tumor targeting and cause obvious systemic adverse reactions. The development of nano-drug particles delivery systems has ushered in a new chapter in precision tumor treatment. Due to the enhanced permeability and retention (EPR) effect caused by anomalous tumor blood vessels, nanoparticles can passively target tumor tissues. However, most nanoparticles are rapidly cleared by the mononuclear phagocytic system, limiting their anti-tumor efficacy. In recent years, cell membrane-coated nanoparticles (CNPs) have shown great potential for application in tumor therapy. CNPs are nano-drug particles wrapped by cell membranes, which can not only exhibit excellent biocompatibility, but also retain some of the biological characteristics of the original cell membrane. CNPs from erythrocyte can extend the blood circulation duration of drugs. CNPs from platelet, CNPs from immunocyte, and CNPs from stem cell all demonstrate a tumor-targeting capability, CNPs from immunocyte can also regulate anti-tumor immunity. CNPs from tumor cell have been extensively researched for their excellent homogenous targeting properties. In this review, we outline the construction process of CNPs, and introduce the roles of CNPs based on various cell membranes in tumor therapy, and discuss their future application prospects and challenges.

Cutaneous melanoma is a highly aggressive and lethal malignant tumor, with an increasing incidence in recent years. Despite the advancements in various treatment approaches for cutaneous melanoma, achieving ideal treatment with conventional treatment strategies remains a big challenge due to factors such as the physicochemical properties of drugs, the complex tumor microenvironment, and surgical site infections. In the last decades, drug delivery systems have shown remarkable potential in the treatment of cancers, the nanoparticles (NPs) exhibit highly tunable capabilities, while hydrogels and microneedles excel in drug reservoirs, wound dressings, and transdermal delivery. This article introduces the latest research progress of these three drug delivery systems in the treatment of cutaneous melanoma, then functionally positions these delivery systems according to the requirements of different treatment stages, and further analyzes their clinical translation prospects, aiming to provide references for innovative drug development in this field.

Glycyrrhizae Radix et Rhizoma (GRR) is widely used in ancient and modern Chinese herbal compounds, which can moderate property of herbs with the effect of improving efficacy and reducing toxicity. Exploring the scientific connotation of GRR compatibility theory is of great significance for guiding the clinical application of GRR compatibility and related drug development. Based on summarizing the application and research status of GRR compatibility, this paper mainly reviews the research progress on the mechanisms of GRR compatibility in terms of enhancing efficiency, alleviating property, reducing toxicity, and incompatibility from the perspective of molecular self-assembly, and simultaneously expounds on the research progress of innovative formulation design and application of GRR components based on molecular self-assembly, so as to provide reference and guidance for further explaining and enriching the scientific connotation of GRR compatibility theory, and to provide certain theoretical and practical basis for the design and development of innovative formulations based on GRR component self-assembly.

Behçet's syndrome (BS) is a rare chronic immune/inflammatory disease characterized by recurrent oral aphthous ulcers and a variety of other systemic manifestations that can lead to many severe complications and even death. The exact pathogenesis of BS has not yet been fully elucidated. However, in recent years, several studies have identified neutrophil hyperfunction and enhanced chemotaxis as important components of the pathogenesis of BS. In this paper, the latest research progress on the involvement of neutrophil in the pathogenesis of BS is reviewed from three aspects: namely neutrophil hyperactivation, the release of neutrophil extracellular traps NETs (NETs), and the generation of excess reactive oxygen species (ROS), aiming to provide a theoretical basis for the pathogenesis and clinical diagnosis and treatment of BS. Furthermore, based on the key role of neutrophils in the disease process of BS, this paper also reviews the progress of research on neutrophil-targeted drug delivery systems, to provide a reference for the targeted regulation of neutrophils in treating BS.

Mitochondria, as the central hub regulating cellular metabolism and apoptosis, exhibit dynamic networks (fusion/fission, autophagy) whose dysregulation is closely linked to the pathogenesis of cancer, neurodegenerative diseases, and metabolic disorders. Conventional drug delivery systems fail to overcome the challenges of lysosomal escape and transmembrane delivery, resulting in systemic toxicity and targeting failures that severely limit clinical applicability. Recent mitochondrial-targeting strategies have achieved breakthroughs through an innovative tripartite framework—"precision delivery, dynamic responsiveness, and synergistic therapy" significantly enhancing delivery efficiency and therapeutic precision. However, heterogeneity in membrane potential, unclear mechanisms of carrier-biointerface interactions, and challenges in manufacturing scalability remain major bottlenecks for clinical translation. Future efforts must integrate pharmaceutics, synthetic biology, and computational materials science to develop closed-loop feedback-based intelligent carriers and establish standardized preclinical evaluation systems, thereby accelerating the implementation of precision medicine.

C-Glycosyltransferases (CGTs) are natural biocatalyst responsible for the formation of C-glycosides, transferring sugar moieties from activated nucleotide sugar donors to acceptor substrates and establishing C-C glycosidic bonds. C-glycosides show diverse pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, and antitumor activities, and comparing with O-glycosides, C-glycosides exhibit better pharmacological properties due to their glycosidic bonds being more resistant to chemical and biological degradation. Thus, CGTs have shown considerable potential in drug research and development. Although research on CGTs has made significant progress, with respect to the number of identified CCTs and the understanding of catalytic mechanism, there is still a large distance between CGTs and extensively studied O-glycosyltransferases (OGTs). The reported crystal structures of CGTs have provided a good elucidation of the recognition of sugar donors. However, the limited acceptor-bound structure hinders the comprehensive understanding of their catalytic mechanisms, thereby affecting the application in the fields of bioengineering and pharmaceuticals. Here we summarize the information of identified CGTs for natural product regarding substrate types, protein structures, proposed catalytic mechanisms, and CGT-related engineering and applications, aiming to bring out some new ideas for future research and development.

The study aims to establish and validate a mouse model of depression with concurrent heart and spleen deficiency using a combined induction method involving neurobehavioral assessments and traditional Chinese medicine (TCM) syndrome evaluation. The model was constructed via modified electroshock and forced swimming protocols, and compared to a chronic unpredictable mild stress (CUMS)-induced depression model. Syndrome validation was performed using TCM prescriptions. Depression assessments revealed that the mice in the combined induction model exhibited significant depressive-like behaviors compared to controls. Moreover, the 5-hydroxytryptamine (5-HT) and dopamine (DA) levels in the brain tissue and serum were significantly decreased (P < 0.01, P < 0.05), while corticosterone (Cor) levels were significantly increased (P < 0.01). TCM syndrome evaluation demonstrated symptoms including mental fatigue, delayed responses, insomnia, reduced appetite (P < 0.01), and diminished tongue color intensity (P < 0.01). Cardiovascular and digestive functions were impaired (P < 0.01, P < 0.05), with a decreased spleen index (P < 0.01). Validation experiments indicated that paroxetine alleviated the depressive-like behaviors, while the classic TCM formula Guipi Decoction significantly modulated depression-related biomarkers and syndrome indicators. A mouse model of depression with both heart and spleen deficiency can be successfully established using the modified electroshock combined with forced swimming method. Animal experiments were conducted with the approval and supervision of the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics number: 2023031303).

This study aims to investigate the effects of nicotine exposure during puberty on cocaine addiction behaviors in adult rats and to investigate the underlying mechanisms. Male Wistar rats, aged 30 days, were divided into two groups: saline-exposed group and nicotine-exposed group. The nicotine-exposed group received subcutaneous injections (sc) of 0.3 mg·kg^-1 nicotine solution three times daily for 15 consecutive days, while the saline-exposed group received an equal volume of saline. On day 60 post-birth, blood was collected from the orbital sinus to separate serum. On day 62, rats underwent jugular vein catheterization surgery and self-administration (SA) training for cocaine, which lasted for 10 consecutive days. The fixed ratio (FR) schedule was gradually increased. After training, rats displayed stable nose-poke behavior for cocaine seeking. Dose-response tests (DR) and progressive ratio tests (PR) were performed to examine whether nicotine exposure during adolescence influenced cocaine addiction in adulthood. This experiment was approved by the Animal Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: 00004401). In the DR test, nicotine-exposed rats showed significantly higher numbers of effective cocaine injections at doses of 0.03, 0.1, and 0.3 mg·kg^-1 compared to the saline-exposed group. The nicotine-exposed group exhibited more pronounced craving for cocaine. In the PR test, at 0.75 mg·kg^-1 cocaine dose, nicotine-exposed rats tended to have higher breakpoints (BP) than the saline-exposed group. Cytokine antibody array and ELISA of serum revealed that CCL5 level in the nicotine-exposed group was significantly higher than that in the saline-exposed group. Moreover, in the DR test, the number of cocaine injections obtained at 0 and 0.3 mg·kg^-¹ cocaine doses correlated significantly with CCL5 levels. In conclusion, nicotine administration during puberty in rats can significantly increase their addiction to cocaine and self-administration behavior in adulthood, exhibiting distinct drug dependence characteristics. The content of CCL5 in rat serum is positively correlated with cocaine addictive behavior.

The development of antitumor live microbial agents represents an emerging frontier in cancer immunotherapy. Attenuated Salmonella VNP20009 stands as one of the most extensively studied oncolytic bacterial strains, demonstrating remarkable tumor-targeting specificity with 10³–10⁴-fold higher distribution titers in tumor tissues compared to normal tissues, alongside significant antitumor efficacy. However, the molecular mechanisms underlying its tumor-targeting properties and antitumor activity remain elusive, hindering further strain optimization. As aromatic amino acids serve as essential nutrients for bacterial growth, their biosynthesis in Salmonella is primarily regulated by the aroC gene. To investigate the role of aromatic amino acid biosynthesis in VNP20009's antitumor activity, we constructed an aroC-deficient strain (VNP ΔaroC) using CRISPR/Cas9 technology. Systematic evaluations were performed to assess: ① tolerance to extracellular stresses (pH, H₂O₂) in vitro; ② invasive capacity against B16F10 melanoma cells; ③ proliferative capacity within tumor cells; ④ antitumor efficacy and biodistribution in B16F10 tumor-bearing mice. Experimental results revealed that VNP ΔaroC exhibited comparable growth profiles to wild-type VNP20009 under varying pH and H₂O₂ conditions. However, its colony growth rate on solid medium under identical pH and H₂O₂ conditions was significantly reduced relative to VNP20009. Furthermore, the invasive and proliferative capacities against B16F10 melanoma cells were markedly diminished compared to the wild-type strain. In murine models, VNP ΔaroC demonstrated reduced systemic toxicity but concurrently showed attenuated antitumor efficacy and tumor-targeting specificity. These findings establish aroC as a critical gene governing both therapeutic potency and tumor-targeting capability of VNP20009. This study provides valuable insights for further synthetic biological engineering of oncolytic bacterial strains. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Nanjing University (approval No: IACUC-2003167).

This study employed an acute stress mouse model to systematically explore the regulatory effects of Pien Tze Huang (PTH) on myeloid and lymphoid immune cells in acutely stressed mice. C57BL/6J mice were randomly divided into a control group, an acute restraint stress group, and high dose and low dose Pien Tze Huang groups with acute restraint stress. Except for the control group, mice in the other groups were administered drugs by gavage for 7 consecutive days before the experiment. On the 7^th day, after drug administration, restraint stress was applied for 18 h, followed by an additional 2 days of drug administration. Mice were then sacrificed to measure the weights of the spleen and thymus and calculate organ indices. Flow cytometry was used to detect the numbers and proportion of myeloid and lymphoid immune cells in the spleen and peripheral blood of mice. The phagocytic capacity of peritoneal macrophages in mice was also measured. The results show that acute restraint stress increased the proportion of myeloid cells (eosinophils, macrophages) in peripheral blood and the spleen of mice, while decreasing the proportion of lymphoid immune cells (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, natural killer T cells, B cells). It also reduced the phagocytic function of peritoneal macrophages in mice. After treatment with PTH, the proportion of myeloid cells (eosinophils) in peripheral blood and the spleen of stressed mice decreased, while the proportion of lymphoid immune cells (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, natural killer T cells, B cells) increased. Additionally, the phagocytic function of peritoneal macrophages improved. This study shows that PTH can alleviate immune disorders caused by acute stress, providing experimental evidence for its use in treating psychosocial stress-related diseases. This experiment was approved by the Animal Ethics Committee of Jinan University (Approval No.: IACUC-20240220-14).

To evaluate the effect of tandospirone (TS) on fentanyl (FEN)-induced respiratory depression and its impact on fentanyl's analgesic and sedative effects, a rat model of respiratory depression was established using FEN. After drug administration, respiratory frequency (F), tidal volume (TV), expiratory volume (EV), and enhanced pause (PENH) were measured using plethysmography. Blood oxygen saturation (SaO₂) was measured using a non-invasive pulse meter. The acetic acid writhing test, hot-plate test, and spontaneous activity test were used to evaluate the number of writhes, reaction time, and locomotor activity in mice. The righting reflex test was used to measure the loss rate and immobility time in rats [this experiment was approved by the Institute of Military Medicine Experimental Animal Management and Utilization Committee (approval number: IACUC-2023-001C)]. Compared with the respiratory depression model group (FEN 160 μg·kg^-1), the changes of F, TV, EV, PENH, SaO₂ in rats at the same time points after pre-treatment and treatment of different doses of TS were improved. TS (2 mg·kg^-1) and TS+FEN groups reduced the number of writhing movements, total distance of spontaneous activity and increased the maximmal possible effect (MPE), indicating that TS has its own analgesic and sedative effect and enhances the analgesic and sedative effect of FEN. The increase in the median effective concentration (EC₅₀) of loss of the righting reflex (LORR) and the reduction in immobilization time confirm that preconditioning with TS has a protective effect against FEN poisoning. In conclusion, TS ameliorates FEN-induced respiratory depression, and it possesses inherent sedative and analgesic effects. When co-administered with FEN, TS can enhance the analgesic and sedative effects of FEN. TS could serve as a non-opioid medication to improve opioid-induced respiratory depression and warrants further development and research.

Metformin demonstrates significant hypoglycemic efficacy, yet its clinical application is limited by gastrointestinal adverse reactions. The integration of Chinese and Western medicine through gut microbiota modulation provides a novel strategy for addressing metformin intolerance. Animal experiments were approved by the Animal Ethics Committee of Beijing Friendship Hospital, Capital Medical University (Approval No.: 23-2043). C57BL/6J mice were fed a high-fat diet (HFD) for 4 weeks, followed by 7 days of high-dose metformin administration (250 mg·kg^-1, bid) to establish a diarrhea model (HFDM). Additional groups included a normal chow diet group (NCD), HFD group, and combination group (HFDMB; co-administered baicalin while establishing the mouse model of diarrhea, 100 mg·kg^-1, bid). Observations of fecal morphology, diarrhea score, and fecal water content revealed that baicalin alleviated metformin-induced early diarrhea. Full-length 16S rRNA sequencing of fecal samples demonstrated that baicalin reduced the relative abundance of diarrhea-associated bacteria (Shigella sonnei, Enterococcus gallinarum, Enterococcus hirae) while increasing beneficial bacteria (Lactobacillus johnsonii, Ligilactobacillus murinus, Limosilactobacillus reuteri). Targeted bile acid quantification of colonic contents revealed elevated levels of primary bile acids (e.g., TCDCA, TCA) in the HFDM group, which were normalized by baicalin co-treatment. Histopathological analysis of colonic tissues via H&E staining and immunohistochemical labeling of tight junction proteins (ZO-1 and occludin) indicated that baicalin mitigated metformin-induced colonic damage and enhanced tight junction protein expression. In conclusion, this study elucidates that baicalin alleviates metformin-induced early diarrhea by modulating gut microbiota-bile acids-gut barrier, offering a scientifically grounded integrated therapeutic approach for clinical metformin intolerance.

In order to clarify the anti-fouling active components of the marine-derived fungal strain Aspergillus terreus GXIMD00546, its fermentation products of the rice medium were isolated by silica gel column chromatography and purified using HPLC. One new compound asperterrestide C (1) and 12 known compounds territrem B (2), methyl-3, 4, 5-trimethoxy-2-(2-(nicotinamido)benzamido)benzoate (3), butyrolactone Ⅰ (4), terrien (5), (1R, 2S)-2-hydroxy-5-oxo-3-((E)-prop-1-en-1-yl)cyclopent-3-en-1-yl acetate (6), (1S, 5R)-5-hydroxy-4-oxo-2-((E)-prop-1-en-1-yl)cyclopent-2-en-1-yl acetate (7), 4-hydroxykigelin (8), monacolin K (9), methyl ester of lactone ring-opened monacolin K (10), butyrolactone Ⅶ (11), aspernolide A (12), and epi-aszonalenin C (13) were identified by the detailed data analysis of NMR sepectra, high-resolution mass spectrometry spectra and the comparison with literatures. The new compound asperterrestide C (1) is a cyclopeptide with rare aminomethylation modifications. Compounds 1-3, 6, 7, 9, 11, 12 showed clear anti-fouling activities against the attachment of barnacle larvae in the EC₅₀ ranges of 0.12-12.5 μg·mL^-1 with low toxicity. Compounds 1, 2, 4, 9-12 also exhibited acetylcholinesterase inhibitory effects with EC₅₀ range of 17.16-55.77 μg·mL^-1. Compounds 4 and 11 have broad spectrum antibacterial activity against human pathogenic bacterium methicillin-resistant Streptococcus aureus (MRSA), and fouling bacteria Methanococcus janaschii (MJ), Vibrio pelagius (VP), and V. Rotiferianus (VR).

Nine flavonoid glycosides were isolated from water extract of the fruits of Lycium ruthenicum Murr. by using various chromatographic methods, including D-101 macroporous adsorption resin, silica gel, ODS, Sephadex LH-20 and semi-preparative HPLC. The structures of the isolated compounds were identified as laricetrin-3-O-β-D-glucopyranoside-7-O-[4′′′′-O-(E)-p-coumaroyl-α-L-rhamnopyranosyl-(1′′′′→6′′′)]-β-D-glucopyranoside (1), (2S)-naringenin-5-O-α-L-rhamnopyranosyl(1′′′→6′′)-β-D-glucopyranoside (2), kaempferol-3-O-robinobioside (3), quercetin-3-O-rutinose (4), isorhamnetin-3-rutinoside (5), kaempferol-3-β-D-glucopyranosyl(1→4)-α-L-rhamnopyranoside (6), prunin (7), (2S)-helichrysin A (8), 2′-O-β-D-glucopyranoside (9) by spectroscopy methods (1D NMR, 2D NMR, MS, etc.). Compounds 1 and 2 were new flavonoid glycosides, named lyciuflavonoid A and lyciuflavonoid B. Compounds 6 and 9 were isolated from L. ruthenicum for the first time. Compound 9 has an inhibitory effect on α-glucosidase with an IC₅₀ of (76.14 ± 4.64) μmol·L^-1.

The study aims to interpret the formula-syndrome correspondence of pacifying liver-subduing Yang and liver Yang hyperactivity from formulas containing Uncaria rhynchophylla based on metabolomics technology, and establish an efficacy evaluation method for these formulas. The rat model of hypertension with liver Yang hyperactivity syndrome was established by intragastrically administering Fuzi Decoction to spontaneously hypertensive rats. Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDZYY20240304033). Tianma Gouteng Decoction, Lingjiao Gouteng Decoction, and Qingnao Jiangya Tablets were respectively administered. The blood pressure, appearance, pain threshold, facial temperature, level of irritability, and 24-hour water intake of the rats were observed. Ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry and metabolomics were used to analyze differential metabolic markers in the serum of rats treated with formulas containing Uncaria rhynchophylla, and metabolic pathway analysis was carried out. Meanwhile the intervention effects of formulas containing Uncaria rhynchophylla were judged according to the changes in the ion intensity of differential metabolites combined with macroscopic data, and partial least squares (PLS) regression analysis was applied to screen significantly differential metabolites. The identified common differential metabolites were regarded as the core metabolic phenotypes of hypertension with liver Yang hyperactivity syndrome. By integrating macroscopic data and metabolic phenotypes, an evaluation method for the syndrome efficacy of Uncaria-based prescriptions was constructed. A total of 35 common differential metabolic markers were identified in this experiment. Among them, 24 differential metabolites decreased in the model group and increased after the intervention of formulas containing Uncaria rhynchophylla, while 11 differential metabolites showed the opposite trend. Metabolic pathway enrichment analysis showed that the intervention pathways were mainly associated with arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis, and glycerophospholipid metabolism. Through PLS regression analysis, 14 significant differential metabolites were obtained, mainly involving three metabolic pathways: arachidonic acid metabolism, biosynthesis of unsaturated fatty acids and glycerophospholipid metabolism. The established efficacy evaluation method indicated that Tianma Gouteng Decoction showed the most significant intervention effect, which was consistent with the theory of traditional Chinese medicine. This study discovered the common factors of formulas containing Uncaria rhynchophylla in intervening hypertension with liver Yang hyperactivity syndrome, and revealed the metabolic basis of the correspondence between these formulas and liver Yang hyperactivity syndrome. The efficacy evaluation method was built to objectively quantify formulas containing Uncaria rhynchophylla, and offers evidence for clinical research.

In this study, LHCGR(-Ex10)-CRE-luc-HEK293 cell line and LHCGR-CRE-luc-HEK293 cell line were constructed according to the cAMP signaling pathway activated by luteinizing hormone (LH) binding to the receptor. The biological activity of LH was detected by luciferase detection system, and the relative titer of samples was calculated by four parameter fitting analysis. The method conditions were optimized, and the specificity, relative accuracy, precision and linearity of the method were verified. The results showed that there was a dose-response relationship between the concentration of LH and the expression of reporter gene, and it conformed to the four-parameter curve. After optimization, the conditions were determined as follows: the initial concentration of LH was 200 nmol·mL^-1, 6-fold serial dilution, 10 concentrations, the number of cells per well was 30 000, and the incubation time was 6 h. It is proved that the method has strong specificity, good accuracy, precision and linearity. This study successfully established and validated a reporter gene method to detect LH biological activity, which can be used for LH biological activity detection and quality control. With the increasing demand for the research and development of LH biosimilar drugs, the establishment of a stable and simple activity assay method to evaluate the biological activity of LH can provide technical support for the quality control of LH products and a powerful tool for the comparative study of similar products.

Forsythia suspensa is one of the great medicinal herbs. At present, research on the active ingredients of Forsythia suspensa mainly focuses on Forsythin, Forsythiaside and Phillygenol, etc. Polysaccharides show increasingly significant pharmacological functions, which may be associated with the efficacy of Forsythia suspensa in clearing heat and removing toxins and dispersing wind and heat. Therefore, it is important to study the green Forsythiae Fructus polysaccharide and ripe Forsythiae Fructus polysaccharide. In this paper, we have separated and purified green Forsythiae Fructus polysaccharides and ripe Forsythia Fructus polysaccharides by gel chromatography and comparatively analysed the structures of the two groups. Comparison of the anti-inflammatory activity of green and ripe Forsythiae Fructus polysaccharides by lipopolysaccharide (LPS)-induced macrophage hyperinflammation model in RAW264.7 mice, the mechanism of action of polysaccharides with powerful anti-inflammatory activity has also been preliminarily investigated using cellular metabolomics. It was determined that the weight average molecular weight of green Forsythiae Fructus polysaccharide was significantly higher than that of ripe Forsythiae Fructus polysaccharide. The type of monosaccharide that accounted for the largest proportion of the monosaccharide composition of both green and ripe Forsythiae Fructus polysaccharides was Gal-UA, followed by Glc methylation results indicate that the major linkage of both polysaccharides is 4-Gal(p)-UA. The results of the anti-inflammatory activity study demonstrated that both polysaccharides exhibited anti-inflammatory activity, with green Forsythiae Fructus polysaccharide displaying a more powerful anti-inflammatory effect. A metabolomic study identified 18 distinct metabolites in RAW264.7 cells following the action of the active ingredient of green Forsythiae Fructus polysaccharide, compared with the control group. These metabolites were primarily involved in arginine biosynthesis, alanine metabolism, and other pathways that are closely associated with oxidative stress and the inflammatory response. This paper compares the structure and activity of polysaccharides, one of the bases for the medicinal effects of green Forsythiae Fructus and ripe Forsythiae Fructus, and provides a solid foundation for further studies on green Forsythiae Fructus and ripe Forsythiae Fructus.

The objective of this study to explore the active components and action mechanisms of Tufuling Qiwei powder (TFLQW) in the treatment of ulcerative colitis (UC) based on serum migration components, network pharmacology and experimental validation. The UC mouse model was induced using dextran sulfate sodium (DSS), and TFLQW was administered at different concentrations via gavage. The inflammatory factors in mouse serum were detected using the ELISA, and the mouse colon tissues were evaluated with HE staining and pathological tissue scoring to confirm that TFLQW could alleviate the UC phenotype in UC mice. Subsequently, the HPLC-Q-Exactive-MS technology was used to analyze the serum migration components of TFLQW, and 20 serum migration components were identified through spectral library searching and mass spectrometry identification processes. The Swiss Target Prediction database was used to predict the target of the components, and UC targets were searched in disease databases GeneCards, OMIM, and DisGeNet. Venny 2.1.0 software was used to draw a Venn diagram to obtain 113 intersection targets. The "drug-components-targets-disease" network was constructed using Cytoscape 3.8.0 software, and the Centiscape 2.2 was used to screen for core components. Components such as palmatine, berberine, jatrorhizine, coptisine, chrysophanol, and resveratrol in TFLQW may be the active substances exerting the therapeutic effect. The String database was used to analyze protein-protein interaction (PPI) and to screen for key targets, suggesting that TFLQW exerts the therapeutic effect on UC by targeting STAT3, PIK3R1, SRC, PIK3CA, MAPK1, and AKT1, among others. The David database was used for GO enrichment analysis and KEGG pathway analysis of the intersection targets, and revealed that the pathways involved in TFLQW treatment of UC mainly include cancer, PI3K/AKT and C-type lectin receptor signaling pathways. Molecular docking was performed on key targets and core components, and PIK3CA binded well with various active components. Western blot was used to detect the protein expression of PI3K/AKT signaling pathway in mouse colon tissue. This study has confirmed the therapeutic effect of TFLQW on UC and preliminarily identified the potential active components and signaling pathways of TFLQW in treating UC. These findings provide a reference for in-depth research into the material basis and action mechanisms of the compound preparation, and also offer a theoretical basis for the clinical application of TFLQW. The animal welfare and experimental procedures were approved by the Medical Ethics Committee of Inner Mongolia Medical University (ethics approval number: YKD202302093).

To effectively determine the content of characteristic components in imported Dragon's Blood (DB) and domestic Chinese Dragon's Blood (CDB), this study established a multiple reaction monitoring (MRM) method based on ultra-high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (UHPLC-Q-Trap-MS). Chromatographic separation was achieved using an ACQUITY UPLC BEH C₁₈ column (2.1 mm × 100 mm, 1.7 μm) at 30 ℃ with a mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.3 mL·min^-1 under gradient elution. The method successfully separated and quantified six characteristic components in DB and eleven in CDB within 22 minutes. The developed approach demonstrated excellent specificity, enabling rapid and efficient determination of 17 components. All analytes exhibited strong linearity (R² > 0.99), and the average recovery rate was 93.58%-105.82%. Results revealed that imported Dragon's Blood contained higher levels of dracorhodin, (2S)-5-methoxyflavan-7-ol and (2S)-5-methoxy-6-methylflavan-7-ol, while domestic Chinese Dragon's Blood was rich in loureirin B, loureirin D and pterostilbene, albeit with significant variations among different batches. These findings provide critical references for quality control and standardization of DB and CDB, as well as the insights for distinguishing similar traditional Chinese medicines.

Using the heterobifunctional crosslinker 3-(2-pyridinedithio) propionate N-succinimidyl ester (SPDP) as a coupling agent, doxorubicin (DOX) was coupled with pamidronate sodium via a chemical cross-linking method to prepare bisphosphonate-modified doxorubicin (P-DOX). The obtained product was characterized by Fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy. To evaluate the in vitro bone targeting of the drugs, the binding amount of drugs onto calcium phosphate was measured, and the in vitro drug release behavior was measured under different pH values and in the presence of cysteine. Finally, to evaluate the effect of phosphorylated doxorubicin on the cellular activity of normal bone tissue and its inhibitory ability on the growth of tumor cells, the drug was co-cultured with osteogenic precursor cells, prostate cancer cells, and osteosarcoma cells, respectively. Infrared spectra analysis showed that DOX/bisphosphonate complex was successfully synthesized. The drug adsorption experiments showed that the adsorption rate of modified doxorubicin onto hydroxyapatite was increased by about one time, and effective release was achieved in a cysteine-rich environment and acidic environment. Cell co-culture experiments showed that compared with traditional doxorubicin, phosphorylated doxorubicin accumulated less in osteogenic precursor cells, effectively reducing the toxicity of chemotherapeutic drugs to normal bone tissue cells. In addition, phosphorylated doxorubicin could be effectively taken up by tumor cells, which effectively inhibit the proliferation, migration, and invasion of tumor cells, and promote apoptosis and necrosis of tumor cells. Thus, the synthesis of doxorubicin-bisphosphonate conjugates provides a new solution for the treatment of malignant bone tumors and provides an important reference for the development of more targeted antitumor drugs.

This study investigates the effects of various curing methods on the dissolution, in vitro release, and pharmacokinetics of trans-cinnamaldehyde (CA). CA was cured and characterized using porous silica adsorption and β-cyclodextrin inclusion. The dissolution and release profiles were determined, followed by conducting comprehensive pharmacokinetic studies in SD rats. The successful preparation of the two cures was verified by analytical techniques such as differential scanning calorimetry, X-ray diffraction analysis, and Fourier transform infrared spectroscopy. Both curing methods significantly increased the cumulative dissolution and cumulative release of CA at pH 1.2, 4.5 and 6.8. In comparison to free CA, the use of porous silica adsorption not only enhanced the in vitro release of CA but also significantly increased its C_max and the AUC_0-∞ in rats. β-Cyclodextrin inclusion delays CA release in vitro, decreases C_max in vivo in rats and significantly increases AUC_0-∞. All animal experiments were approved by the Animal Ethics Committee of Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine (Ethics Approval Number: AEWC-20220815-230). Our findings revealed that porous silica adsorption significantly enhanced both the in vitro release and the in vivo uptake rate of trans-cinnamaldehyde. Conversely, β-cyclodextrin inclusion of CA led to a noticeable retardation in its in vitro release and a moderate decrease in the in vivo uptake rate.

Traditional Chinese medicine decoction is a polydisperse system composed of multiple phases. On the basis of phase separation, conducting chemical composition analysis and efficacy evaluation are helpful to clarify the transformation rules of the effective substances of traditional Chinese medicine. In this study, the classical prescription, Ling-Gui-Zhu-Gan Decoction was used as the object to track the real-time change of the particle size of the decoction during the boiling process; different phases were separated by centrifugation and ultrafiltration, and various types of chemical components were analyzed. The therapeutic effect of the decoction and its representative phase was evaluated by establishing an in-house mouse obstructive kidney model. The results showed that the mixing degree of particle size distribution decreased during the boiling process of Ling-Gui-Zhu-Gan Decoction, and finally stabilized around 200 nm. After phase separation, small molecules, polysaccharide, protein, lipids, RNAs and other components were mainly distributed in the colloidal phase. The whole decoction and the colloid phase showed almost equal activity in alleviating the process of obstructive renal fibrosis. This investigation further confirmed that the chemical components of different Chinese herbs were redistributed and aggregated in the colloidal phase during the boiling process of Ling-Gui-Zhu-Gan Decoction, which became the main form of the whole decoction to play its therapeutic effect. This provides a basis for understanding and exploring traditional Chinese medicine from the perspective of phase state. The animal experiment has been approved by the Animal Experiment Ethics Committee of Nanjing University of Chinese Medicine (No: 202501A012).

The quality of Panax notoginseng medicinal herbs affects their clinical treatment efficacy. At present, the quality of Panax notoginseng varies greatly, and its quality control mainly relies on saponin compounds, which cannot systematically reflect the quality of Panax notoginseng medicinal materials. This study is based on the collection of Panax notoginseng medicinal materials from different production areas, using micromethod, UV visible spectrophotometry, and high-performance liquid chromatography to quantitatively analyze multidimensional indicators that affect the efficacy and formulation of Panax notoginseng. The results showed that the production area with high content of macromolecules (amylum, cellulose, lignin) in Panax notoginseng was Yanfangxiang, Zhanyi, Qujing, Yunnan. The production area with high content of total polysaccharides was Malipo, Malizhen, Wenshan, Yunnan. The production area with high content of total flavonoids was Qinglongzhen, Huaning, Yuxi, Yunnan. And the production area with high content of Panax notoginseng was Dianshaxiang, Xundian, Kunming, Yunnan. The production area with high content of total saponins was Malipo, Malizhen, Wenshan, Yunnan. Based on hierarchical clustering and orthogonal partial least squares-discrimination analysis (OPLS-DA), dencichine, total polysaccharides, amylopectin, and cellulose were identified as potential biomarkers for distinguishing Panax notoginseng medicinal materials from different production areas. Using the global geographic information system for medicinal plants, 19 ecological factors of Panax notoginseng production areas were obtained, and the impact of ecological factors on the accumulation of various components of Panax notoginseng was determined through correlation analysis. Among them, the annual precipitation, the isothermality, the mean diurnal range, the min temperature of coldest month, the mean temperature of warmest quarter, the precipitation of wettest quarter, and the precipitation of warmest quarter were key ecological factors affecting the quality of Panax notoginseng. In summary, this study comprehensively evaluated the quality of Panax notoginseng from different origins, revealed the key ecological factors that affect its authentic quality, and provided a reference for subsequent quality control and rational site selection of Panax notoginseng.