Objective To explore the “medicine-efficacy” associations of traditional Chinese medicine (TCM) in the treatment of sepsis, identify core herbsrelated to reducing mortality and improving key clinical outcomes such as the acute physiology and chronic health evaluation II (APACHE II) score, and provide evidence-based references for TCM-assisted treatment of sepsis. Methods A systematic search of Chinese and English databases was conducted up to September 2024 to collect clinical studies on TCM compound prescriptions for sepsis. A comprehensive sepsis TCM formula database was established. Nine machine learning algorithms were compared using ten-fold cross-validation, and the optimal model for each clinical outcome was interpreted through the Shapley additive explanations (SHAP) method to identify key herbs and their contribution directions. Results The multilayer perceptron showed the best performance in predicting TCM syndrome scores, overall effectiveness, inflammatory and immune indicators, biochemical parameters, organ dysfunction scores, and mortality; logistic regression performed best for blood gas analysis along with gastrointestinal function and intestinal mucosal barrier outcomes; and the support vector machine achieved optimal predictive performance for routine blood tests and APACHE II scores. SHAP analysis revealed that Dihuang (Rehmanniae Radix), Zhishi (Aurantii Fructus Immaturus), Huangqi (Astragali Radix), Fuzi (Aconiti Lateralis Radix Praeparata), Huangqin (Scutellariae Radix), and Houpo (Magnoliae Officinalis Cortex) had positive contributions across outcomes such as mortality, APACHE II score, inflammatory markers, and gastrointestinal function, forming the core nodes of the “medicine-efficacy” network. Conclusion This study established a clinically oriented “medicine-efficacy” association network through multi-model comparison and explainable machine learning analysis. The findings highlight the potential key roles of several core herbs in improving major clinical outcomes of sepsis, providing data support and evidence-based basis for precise syndrome differentiation and medication in TCM, as well as for the research and development of new TCMs.

Objective To comprehensively analyze the research trends and focuses of Gouteng (Uncariae Ramulus Cum Uncis) from bibliometric and global patent perspectives, providing forward-looking references for its future clinical application and in-depth research. Methods Literature was retrieved from four databases: China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and Web of Science (WOS) with Uncariae Ramulus Cum Uncis as the keyword. Retrieved publications were imported into NoteExpress for deduplication and screening. Software including Excel, Origin, CiteSpace, and VOSviewer were used to visually analyze the current research status and development trends of Uncariae Ramulus Cum Uncis in domestic and international publications, covering publication trends, national distribution, publication institutions, journal of publication, authors, and keywords. The Incopat patent database was searched to analyze global patent applications related to Uncariae Ramulus Cum Uncis, including trends in patent applications, geographical distribution, applicants, and technology fields. Results A total of 1 713 Chinese publications and 594 English publications met the inclusion criteria. China was the primary contributor to publications, with international attention increasing gradually in recent years. Core research teams have emerged in this field, but collaboration among institutions requires strengthening. In recent years, there has been an overlap in the research hotspots of Chinese and English literature in the field of Uncariae Ramulus Cum Uncis, both focusing on the pharmacological components and action mechanisms of Uncariae Ramulus Cum Uncis. Chinese studies specifically emphasize Tianma Gouteng Decoction and its use in hypertension treatment, identifying bioactive compounds and elucidating regulatory mechanisms. English publications focus on phytochemistry, anti-inflammation, antioxidation, and the potential efficacy in neurological diseases. Based on a search of the Incopat patent database, 8 048 patents were initially screened. After merging patent families, 6 251 patents were retained, among which 5 461 were domestic patents, accounting for 87.36% and occupying a dominant position. Conclusion Research in the field of Uncariae Ramulus Cum Uncis shows a trend of continuous expansion and deepening. Overall, it is shifting from traditional Chinese medicine practice to a development path featuring multi-disciplinary collaborative innovation and in-depth analysis of molecular-level mechanisms. Although China dominates international patent applications related to Uncariae Ramulus Cum Uncis, there are key drawbacks: A large number of patents have expired, the degree of transformation and implementation is limited, and market expansion is weak.

Transmembrane transport, as a core process in drug absorption, distribution, and metabolism, directly determines the bioavailability and target tissue distribution of active ingredients in traditional Chinese medicine (TCM). It is a key limiting factor for their systemic exposure and exertion of drug efficacy. The structural diversity and complex mechanisms of TCM components generally lead to low oral bioavailability, which severely restricts their full clinical therapeutic effects and has become a bottleneck in the development of modern TCM formulations. This article systematically reviews the transmembrane transport mechanisms of major active ingredients in TCM, such as flavonoids, alkaloids, saponins, terpenoids, polysaccharides, and organic acids, with a focus on elucidating their structure-transport relationships and the complex regulatory networks involving various transport proteins (e.g., P-glycoprotein, multidrug resistance-associated proteins, organic anion transporting polypeptides, etc.). Given that traditional research has long focused on qualitative and quantitative analysis of components while relatively neglecting the exploration of transmembrane transport mechanisms, hindering mechanism-guided formulation design and optimization. This review further delves into novel enhancement strategies based on transport mechanisms. These include advanced delivery systems, structural modification, efflux protein inhibition, gut microbiota-mediated metabolic enhancement, and synergistic compatibility of TCM ingredients. The aim is to overcome the in vivo delivery barriers of active TCM components, improve the bioavailability of TCM formulations, and ultimately provide insights for achieving precise clinical medication.

ObjectiveTo investigate the protective effect of Rosa roxburghii fermentation broth against acetaminophen (APAP)-induced drug-induced liver injury (DILI) in mice and explore its potential mechanism based on nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. Methods Taking the R. roxburghii juice as the control, the main active component contents and in vitro antioxidant capacity of R. roxburghii fermentation broth were analyzed. A total of 60 Kunming mice were randomly divided into control group, model group, N-acetylcysteine (NAC, 0.15 g/kg) group, and R. roxburghii fermentation broth low-, medium-, and high-dose (5, 10, 20 mL/kg) groups, with 10 mice in each group. All groups were consecutively administered for 7 d, 1 h after the last administration, except for the control group, all other groups received a single intraperitoneal injection of APAP (400 mg/kg) to establish the acute liver injury model. After 12 h of modeling, the mice were anesthetized and euthanized. The intact liver of mice was immediately removed and observed for any visible damage or lesions. The body weight and liver weight were measured and liver index was calculated. Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β in serum, as well as activity of superoxide dismutase (SOD) and levels of glutathione (GSH), malondialdehyde (MDA) in liver tissue were detected by ELISA. Hepatic pathological changes were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expressions of Nrf2, heme oxygenase-1 (HO-1), SOD-1 and catalase (CAT) in liver tissue were detected by qRT-PCR and Western blotting. Neutrophil infiltration was observed by Ly6G immunofluorescence staining, and hepatocyte apoptosis was detected by TUNEL staining. Results Compared with R. roxburghii juice, the contents of total acids, total phenols and total flavonoids in R. roxburghii fermentation broth were significantly increased (P < 0.05), while the content of vitamin C was significantly decreased (P < 0.05), and the total amount of major antioxidant active ingredients were increased, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging rate and Fe³⁺ reducing ability were significantly increased (P < 0.01). Compared with control group, model group showed obvious pathological changes such as hemorrhagic injury in liver, liver index and activities of ALT, AST, levels of inflammatory factors in serum and MDA level in liver tissue were significantly increased (P < 0.001), while GSH level and SOD activity in liver tissue were significantly decreased (P < 0.001). Inflammatory cell infiltration in liver tissue, disruption of hepatic cord structure, and increased necrotic area were observed; The mRNA and protein expression levels of Nrf2, HO-1, SOD-1 and CAT in liver tissue were significantly reduced (P < 0.001); Neutrophil infiltration and hepatocyte apoptosis in liver tissue were significantly increased (P < 0.001). Compared with model group, NAC and R. roxburghii fermentation broth all dose groups could improve the above pathological and biochemical indicators to varying degrees, including reducing visible liver damage and lesions, lowering liver index, down-regulating transaminase activity and inflammatory factor levels in serum, reducing MDA level in liver tissue, increasing GSH level and SOD activity, and up-regulating Nrf2/ARE pathway related genes and protein expressions (P < 0.05, 0.01, 0.001), while significantly inhibiting neutrophil infiltration and liver cell apoptosis (P < 0.05, 0.001). Conclusion R. roxburghii fermentation broth has a potential liver-protective effect against APAP-induced DILI in mice, and its mechanism may be related to the activation of Nrf2/ARE signaling pathway, enhancing antioxidant capacity and inhibiting inflammatory responses.

Objective To explore the mechanism of galangin-induced apoptosis in hepatocellular carcinoma (HCC) based on network pharmacology, molecular docking and cell experiment. Methods Potential targets of galangin were predicted using SwissTargetPrediction and PharmMapper databases, HCC-related targets were collected from GeneCards, TTD and OMIM databases. The intersection of these targets was used to construct a protein-protein interaction (PPI) network via STRING database, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of intersected targets using DAVID platform. Molecular docking of galangin with core targets was validated using AutoDock Vina. Human hepatocellular carcinoma PLC/PRF/5 cells were cultured in vitro, and the effects of galangin on cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry. Western blotting was used to detect the expressions of epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and apoptosis-related proteins. Results Network pharmacology analysis identified 142 common targets between galangin and HCC. PPI network analysis revealed that proteins such as EGFR, Akt and cystein-asparate protease-3 (Caspase-3) may serve as core targets. GO and KEGG analyses suggested that galangin primarily influenced cellular processes by regulating PI3K/Akt signaling pathway. Molecular docking results indicated galangin had strong binding affinity with targets such as EGFR. In vitro experiments confirmed that galangin significantly inhibited PLC/PRF/5 cells viability and induced apoptosis (P < 0.01, 0.001), significantly down-regulated p-EGFR and p-Akt protein expressions (P < 0.05), and significantly up-regulated cleaved Caspase-3 and Caspase-9 protein expressions (P < 0.05, 0.01). Conclusion Galangin may exert its anti-HCC effects by inhibiting EGFR-PI3K/Akt signaling pathway and inducing apoptosis in HCC cells.

Objective To explore the optimal processing method for Dusuanlan (Pleione bulbocodioides) pseudobulbs, this study investigated the effects of scalding method and duration, and drying technique on their morphologies, microstructures, and chemical composition contents. Methods Pseudobulbs of P. bulbocodioides were processed using eight methods: oven direct drying (OD), boiling for 10, 20, 30 min and then drying (B10D, B20D, B30D), steaming for 10, 20, 30 min and then drying (S10D, S20D, S30D), and freeze drying (FD). The contents of 2-O-glucosylbulleyanolide (dactylorhin A), militarine, and batatasin III were quantified by HPLC. By constructing HPLC fingerprints and performing similarity analysis (SA), hierarchical cluster analysis (HCA), and principal component analysis (PCA), the impact of processing methods on the quality of pseudobulbs was evaluated. Structural changes were assessed through examination of macroscopic features, tissue organization, and powdered microscopic characteristics. Using dactylorhin A content, militarine content, batatasin III content, alcohol-soluble extractives, water-soluble extractives, drying rate, moisture content, total ash content, and acid-insoluble ash content as indicators, the effects of eight processing methods on the quality of pseudobulbs were comprehensively evaluated by entropy weight method, analytic hierarchy process (AHP), and technique for order preference by similarity to ideal solution (TOPSIS). Results The values for HPLC fingerprint similarity of the samples obtained from eight methods ranged from 0.681 to 0.994. The freeze-dried (FD) samples exhibited the lowest similarity and were segregated as a distinct cluster in both hierarchical cluster analysis (HCA) and principal component analysis (PCA), while the samples from other seven methods formed a separate cluster. Three common peaks were identified among the 24 common peaks in the HPLC fingerprints: dactylorhin A (peak 7), militarine (peak 9), and batatasin III (peak 15). According to TOPSIS-based comprehensive evaluation, samples steamed for 10 min followed by oven drying (S10D) showed both the highest relative closeness coefficient and the greatest total content of dactylorhin A, militarine, and batatasin III. Conclusion Based on comprehensive multi-index evaluation, steaming for 10 min followed by oven drying (S10D) was identified as an optimal primary processing method for P. bulbocodioides pseudobulbs. This method enhanced the retention of active compounds while being technically straightforward. The study establishes a critical foundation for standardizing processing of P. bulbocodioides pseudobulbs and refining quality standards of Shancigu (Cremastrae Pseudobulbus Pleiones Pseudobulbus) in pharmacopeial monographs.

Objective To construct Ginseng polysaccharide-chitosan oligosaccharide nanoparticles (GP-NPs) and investigate whether their combination with radiotherapy could promote the differentiation of natural killer (NK) cells into highly cytotoxic subsets by activating interferon-I (IFN-I)-mediated Janus kinase 3 (JAK3)/signal transducer and activator of transcription 5 (STAT5) signaling pathway, thereby enhancing the antitumor immune response against non-small cell lung cancer (NSCLC). Methods GP-NPs were prepared via the ionic cross-linking method, and their particle size, dispersibility and stability were characterized. A subcutaneous xenograft model of A549 lung cancer cells in nude mice was established, and the mice were divided into PBS group, radiotherapy alone group and GP-NPs combined with radiotherapy group. The antitumor efficacy and mechanism of GP-NPs combined with radiotherapy were comprehensively evaluated by measuring tumor volume, detecting levels of cytokines in serum via ELISA, analyzing NK cells subsets by flow cytometry, detecting the protein expressions of JAK3/STAT5 pathway through Western blotting and performing histopathological analysis. Results GP-NPs combined with radiotherapy significantly inhibited tumor growth, and the effect was significantly better than that of the simple radiotherapy group (P < 0.01). The levels of interferon-γ (IFN-γ), interleukin-15 (IL-15), granzyme and perforin in serum of combined treatment group were significantly increased (P < 0.01). Flow cytometry showed an increase in the proportion of NK cells infiltration within the tumor (P < 0.01), and a significant increase in the proportion of mature cytotoxic subgroups (CD27^-CD11b⁺) (P < 0.01). Western blotting results showed that the combination therapy significantly activated the JAK3/STAT5 signaling pathway (P < 0.01). Organizational analysis showed that the combination therapy group had increased tumor cell apoptosis, aggravated DNA damage and enhanced NK cell infiltration, with no significant toxicity observed in major organs. Conclusion GP-NPs combined with radiotherapy promote the differentiation of NK cells into highly cytotoxic subsets and enhance their antitumor function by activating IFN-I-mediated JAK3/STAT5 signaling pathway. This combination strategy not only significantly improves the efficacy of radiotherapy but also has good biosafety, providing new experimental evidence and strategic directions for the immunocombination therapy of NSCLC.

ObjectiveTo investigate the intervention effect and related mechanism of hyperoside on sepsis-associated acute kidney injury (SAKI) in mice. Methods A mouse model of SAKI was established by cecal ligation and puncture (CLP). Sham group, model group, dexamethasone (1 mg/kg) group, hyperoside high-, low-dose (50, 25 mg/kg) groups and hyperoside (50 mg/kg) + nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (30 mg/kg) group were set up. After 7 d of drug intervention, the survival curve of mice was plotted. The levels of renal function, inflammatory factors and oxidative stress were detected. The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining. TUNEL staining was used to detect apoptosis in renal tissue cells. Immunohistochemical was used to detect Nrf2 expression in renal tissue. Western blotting was used to detect the expressions of Nrf2, PTEN induced kinase 1 (Pink1) and Parkin proteins in renal tissue. Immunofluorescence was used to detect the co-localization of microtubule associated protein 1 light chain 3B (LC3B) and translocase of the outer mitochondrial membrane 20 (TOMM20) in renal tissue. Lipopolysaccharide (LPS) was used in vitro to induce injury in human tubular epithelial cells (HK-2). After intervention with hyperoside, cell viability, apoptosis and reactive oxygen species levels were detected. Mitochondrial ultrastructure was observed by transmission electron microscopy. Flow cytometry was used to detect mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels to evaluate mitochondrial function. Western blotting was used to detect the expressions of Nrf2, heme oxygenase-1 (HO-1) and mitochondrial autophagy proteins Pink1, Parkin, p62. Results Compared with model group, hyperoside could significantly improve the survival rate of SAKI mice (P < 0.05), alleviate weight loss and renal pathological damage (P < 0.05, 0.01), improve renal function and oxidative stress response (P < 0.05, 0.01), inhibit inflammatory factor levels (P < 0.05, 0.01), up-regulate the expressions of Nrf2, Pink1, Parkin in renal tissue (P < 0.01), and increase the co-ocalization of LC3B and TOMM20 in renal tissue. In vitro experimental results showed that hyperoside (40 μmol/L) could inhibit LPS-induced apoptosis and oxidative stress in HK-2 cells (P < 0.01), increase MMP and ATP levels (P < 0.01), up-regulate Nrf2, HO-1, Pink1, Parkin protein expressions (P < 0.01), down-regulate p62 expression (P < 0.01), promote mitochondrial autophagy, and alleviate mitochondrial damage. In addition, Nrf2 inhibitor ML385 significantly reversed the protective effect of hyperoside on CLP-induced SAKI mice (P < 0.05, 0.01), while weakening hyperoside induced mitochondrial autophagy in HK-2 cells.Conclusion Hypericin may regulate Pink1/Parkin mediated mitochondrial autophagy by activating Nrf2/HO-1 signaling pathway, alleviate mitochondrial dysfunction, alleviate oxidative stress and inflammatory response in SAKI mice, and thus exert renal protective effects.

ObjectiveTo establish the method of multi-index quantification and quality difference evaluation of Zhenzhutougucao (S. tuberculata) from different producing areas. Methods HPLC method was used to establish the content determination method of chlorogenic acid, p-coumaric acid, ferulic acid, vanillic acid, amentoflavone, diosmetin, luteolin, kaempferol, quercetin, lonicerin, rutoside, β-sitosterol and stigmasterol in S. tuberculata. The mobile phase was acetonitrile-0.4 % phosphoric acid, the flow rate was 1.0 mL/min , the detection wavelength was 320 nm and 210 nm, the injection volume was 10 μL, and the column temperature was 30 ℃, water-soluble extract, total ash and acid-insoluble ash were also examined. Principal component analysis and orthogonal partial least squares discriminant analysis were performed on 18 batches of S. tuberculata by SPSS 26.0 and SIMCA14.1 software, and the quality difference markers were determined by the values of variable importance for projection. The CRITIC-TOPSIS method was used to construct the comprehensive quality evaluation model of S. tuberculata. Results The methodological investigation showed that each component showed a good linear relationship and good accuracy.The results of quantitative analysis showed that the contents of 13 chemical components in S. herba from different habitats were (0.867 ± 0.198), (0.586 ± 0.187), (1.454 ± 0.324), (0.347 ± 0.070), (8.262 ± 1.486), (3.247 ± 0.547), (2.397 ± 0.545), (4.464 ± 0.744), (3.224 ± 0.979), (0.266 ± 0.101), (1.153 ± 0.216), (0.706 ± 0.164), (0.079 ± 0.011) mg /g, respectively. The contents of water-soluble extract, total ash and acid-insoluble ash were (25.2 ± 6.4) %, (12.0 ± 2.5) % and (2.2 ± 1.1) %, respectively. The results of multivariate statistical analysis showed that 18 batches of S. herba were obviously divided into three categories. Eight quality difference markers with great contribution were screened and mentioned. According to the contribution degree, they were amentoflavone, quercetin, kaempferol, ferulic acid, luteolin, diosmetin, chlorogenic acid and β-sitosterol. The results of CRITIC-TOPSIS analysis showed that the comprehensive quality of samples S6 (from Jiangsu), S5 (from Henan), S2 (from Shandong), S4 (from Henan), S3 (from Shandong), S1 (from Shandong) and S7 (from Jiangsu) was relatively good. Conclusion There are differences in the quality of S. herba from different producing areas. The established multi-index quantification, chemometrics and CRITIC-TOPSIS method provide experimental basis for improving the quality evaluation system of S. tuberculata.

Objective By systematically analyzing the polyphenolic composition content, astringency intensity, astringency mechanism, and their inherent correlations in Hezi (Chebulae Fructus, CF) pieces with different comminution degrees, this study aims to lay a foundation for its further development and research. Methods The CF was processed into six granule sizes (original granule, extra large granule, large granule, median granule, small granule, fine powder) for sampling. HPLC was employed to quantify the contents of chebulagic acid, gallic acid, chebulinic acid, ellagic acid, corilagin, and 1,3,6-tri-O-galloyl-β-D-glucose. The main chemical composition groups and differences of six kinds of particle size CF samples were analyzed by fingerprint. The astringency intensity of the samples was sensorially evaluated using a visual analogue scale (VAS). These data were utilized to analyze the correlations among comminution degree, polyphenolic composition, and astringency intensity. Furthermore, SDS-PAGE technology was applied to elucidate the underlying astringency mechanism through the protein interaction. Results The total content of six kinds of polyphenolic components displayed significant variation across different granule sizes in the following descending order: median granule > extra large granule > fine powder > large granule > small granule > original granule. The results of fingerprint analysis showed that the main chemical composition groups of the six samples were basically the same. Sensory evaluation revealed that different comminution degrees considerably influenced the perceived astringency intensity, which decreased sequentially as: fine powder > small granule > median granule > large granule > extra large granule > original granule. Correlation analysis identified gallic acid and corilagin as key variables linking comminution degree with astringency perception. SDS-PAGE confirmed that the astringency mechanism primarily involves binding interactions between polyphenolic components and salivary proteins, with the fine powder demonstrating the strongest protein-binding capacity. Conclusion Comminution degree serves as a critical processing parameter governing the dissolution of polyphenolic components and astringency intensity in CF. The sample with a particle size of 4.75—6.70 mm demonstrated the highest content of polyphenolic compounds, whereas the sample with a particle size of 0.15—0.18 mm elicited the most intense perception of astringency. Processing CF to a median granule size (4.75—6.70 mm) is therefore identified as the optimal strategy for balancing polyphenolic component dissolution and oral compliance. This study provides key scientific evidence to support the standardization of CF processing techniques and related product development.