Objective To systematically review the overall landscape of research on hepatotoxicity associated with traditional Chinese medicine (TCM) using bibliometric methods, identify key research areas and emerging trends, and conduct a multidimensional analysis encompassing material basis, mechanisms of action, research methodologies, toxicity reduction strategies, and clinical evaluation, thereby providing reference for TCM safety research and rational application. Methods Chinese and English literature on hepatotoxicity of TCM was retrieved from the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases. The search period spans from January 1982 to July 2025. The CiteSpace bibliometric tool was employed to analyze the temporal distribution of published studies, core authors, key research institutions, high-frequency keywords, and emerging terms, thereby revealing research frontiers and hotspots in this field. Results A total of 552 Chinese-language articles were identified from the CNKI database, while 181 English-language articles were retrieved from the WOS database. The authors with the highest number of publications in both Chinese and English literature are Xiao Xiaohe and Wang Jiabo. The research institutions with the highest number of publications in both Chinese and English literature are Beijing University of Chinese Medicine and Shanghai University of Traditional Chinese Medicine. Bibliometric analysis indicates a steady annual increase in publications on TCM-induced hepatotoxicity. Research hotspots primarily focus on high-risk herbs (e.g., Polygonum multiflorum, Rheum officinale, Tripterygium wilfordii), toxic constituents (e.g., anthraquinones and pyrrolizidine alkaloids), and their molecular mechanisms. Further analysis revealed that research on hepatotoxicity caused by TCM has progressively established a systematic research chain spanning from fundamental mechanism analysis to clinical safety evaluation. Regarding material basis and mechanisms of action, research have focused on high-risk herbs and their active components, revealing multi-pathway synergistic mechanisms of liver injury mediated by metabolic activation, oxidative stress, immune inflammation, and apoptosis. Regarding research methodologies, research have evolved from traditional animal experiments and pathological observations to multidisciplinary approaches including cellular and molecular biology, systems toxicology, network pharmacology, and emerging organoids and liver-on-a-chip technologies. Regarding toxicity reduction strategies, a systematic toxicity reduction system has been established through the approaches of herbal processing, rational combination, formulation optimization, and personalized interventions guided by pharmacogenomics. Regarding clinical evaluation, the continuous refinement of case reporting, causality determination systems, and real-world studies has propelled TCM safety research toward evidence-based and international standards. Conclusion Current research on hepatotoxicity of TCM demonstrates a scientific progression from qualitative descriptions to quantitative analysis, and from empirical judgments to evidence-based conclusions. Future studies should deepen the elucidation of material bases and action mechanisms while strengthening the application of emerging technologies and big data mining. This will enhance the TCM safety evaluation system, providing support for rational TCM use and its modernization.

Objective To investigate the chemical constituents and their anti-inflammatory activity of Cynanchum wilfordii. Methods Various chromatographic techniques including silica gel, ODS, and Sephadex LH-20 column chromatography were employed for the isolation and purification of compounds. Their structures were elucidated through comprehensive spectroscopic analysis including HR-ESI-MS, ESI-MS, ¹H-NMR, ¹³C-NMR, HSQC, and HMBC. The anti-inflammatory activity of the compounds was evaluated using the Griess method. Results Two compounds were isolated and identified as (7'R,8'S)-dehydrodiconiferyl alcohol 9'-O-β-D-xylopyranoside (1) and 3β-[(O-β-D-glucopyranosyl)-oxy]-8β,14β-trihydroxycarda-5,20-(22)-dienolide (2). Compounds 1 and 2 inhibited NO production by 55.16% and 15.34%, respectively, with a median inhibition concentration (IC₅₀) of 41.37 μmol/L for compound 1. Conclusion Compounds 1 and 2 are both new compounds, belonging to lignan and cardenolide types, respectively. They have been assigned the names cynawilforin A (1) and wilforcardenoside A (2). In vitro anti-inflammatory assays indicated that compound 1 exhibits certain anti-inflammatory activity.

Objective To meet the requirements for high-quality development of food-medicine homology products, taking Xiaoer Xiaoshi Granules (XXG, 小儿消食颗粒) as an example, this study established an intelligent-driven granulation process optimization and quality consistency evaluation method for food-medicine homology granules based on the quality by design (QbD) concept. Methods Firstly, the analytic hierarchy process (AHP) was used to assigned weights to critical quality attributes (CQAs) of XXG, with subsequent risk assessment identifying granulation critical influencing factors. Secondly, following single-factor screening of critical influencing factors, the optimal combination of granulation parameters was selected by comparing the Box-Behnken design-response surface methodology (BBD-RSM) and the genetic algorithm-backpropagation neural network (GA-BPNN). Finally, leveraging the medicine-food homology properties of XXG, a quality consistency assessment was performed targeting both chemical attributes (total flavonoid content) and taste quality attribute based on electronic tongue. Results The excipient properties, ethanol volume fraction of wetting agent, ethanol amount, and excipient-to-drug ratio were determined as critical influencing factors, the optimal granulation parameters for XXG were determined as follows: an excipient system of maltodextrin to mannitol at a 2∶1 ratio, an ethanol concentration of 84%, an ethanol amount of 0.18 mL/g, and an excipient-to-drug ratio of 1.5∶1, yielding a comprehensive score of 103.88. Regarding bioactive constituents, the RSD of total flavonoid content across three batches was as low as 1.95%. For instrumental sensory evaluation, the e-tongue response values demonstrated batch-to-batch consistency with RSDs below 3% across all seven sensors. Conclusion The optimized granulation parameter set demonstrated stability and feasibility, and this process optimization approach can offer valuable insights for developing medicine-food homology products and advancing intelligent manufacturing in traditional Chinese medicine.

Objective To reveal the changes of morphological characteristics and amino acid metabolism in fruit of Sinopodophyllum hexandrum at different ripening stages. Methods The morphological characteristics, amino acid content, and related genes expression were determined and analyzed in fruit of S. hexandrum at different ripening stages（S1 to S9）. Results There were significant differences in morphological characteristics（e.g., fruit color, length, and diameter）, amino acid content, and related genes expression during fruit ripening. The fruit length, diameter, fresh weight, and dry weight showed a 2.2, 2.18, 31.42, and 49.05 fold increase at the S6 compared with S1; the content of amino acid were greater at the S5 and S9 than other stages; the 10 candidate genes related to amino acid metabolism [e.g., arginine decarboxylase 2（ADC2）, arogenate dehydratase 6（ADT6）, and asparagine synthetase（AS）] showed a down-regulation to some extent at S4 to S8 compared with S2. Conclusion There were dynamic differences in morphological characteristics, amino acid metabolism and related gene expression levels with fruit ripening. These finding will provide useful references for the development and utilization of S. hexandrum fruits.

Objective Based on the mathematical model of mass transfer, this study aimed to investigate the existence state and transfer principle of chlorogenic acid in the production process of Reduning Injection (RI, 热毒宁注射液) were investigated. Methods Using chlorogenic acid as the detection index, a nanofiltration mass transfer model was established., and choosing the monomer molecular state as the reference, calculated the existence state of chlorogenic acid in the intermediate solution of RI, analyzed the correlation between the change of chlorogenic acid transfer rate and the existence state of chlorogenic acid in the process of production of RI, and explored the intrinsic causes of the difference in the transfer of phenolic acids during the RI concentration process. Results The regression coefficients between the mass transfer coefficients of chlorogenic acid and the power value of solute concentration in the extract solution and the RI intermediate solution were all greater than 0.90, and the nanofiltration mass transfer model was established. chlorogenic acid showed a positive correlation between the ratio of molecular states and the concentration transfer rate in aqueous and ethanol solutions of RI intermediates, and the same trend was observed in solutions of Jinyinhua (Lonicerae Japonicae Flos) and Qinghao (Artemisiae Annuae Herba) intermediates, suggesting that the state of existence of the constituents is the intrinsic cause of the differences in phenolic acid transfer during RI concentration process. In addition, chlorogenic acid was more stable in the molecular state than in the ionic state in the same solution system, and more stable in the ethanol solution than in the aqueous solution in different solvent systems. Conclusion A quantitative calculation method for the molecular state of chlorogenic acid in the intermediate of RI has been constructed, and the positive correlation between its existence state and mass transfer has been initially elucidated, which can provide support for the standardized control of the production process of the preparation.

Objective To optimize the optimal processing technology of different processed products of Huangqin (Scutellariae Radix, SR) [fried Scutellariae Radix (fSR), Scutellariae Radix charcoal (SRc), wine Scutellariae Radix (wSR)], and explore the correlation between sensory traits such as appearance, color, odor, taste, and the main active ingredients. Method The multi-index response surface methodology (RSM) was used, with baicalin, baicalein, wogonoside, wogonin, and appearance trait scores as evaluation indicators. The analytic hierarchy process and entropy weight method were used to calculate the weight coefficients and comprehensive scores of each indicator. Further utilize central combination design (CCD)-RSM to investigate the effects of temperature and processing time (soaking time and the alcohol ratio) on the processing technology. Using electronic sensory technology (electronic eye, electronic nose, electronic tongue) to analyze the response values of samples with different processing levels, and exploring the correlation between sensory traits (color L^*, a^*, b^* value, odor sensor response value, taste sensor response value) and chemical composition through correlation analysis. Results The optimal process parameters were determined as follows: fSR at 205.4 ℃, 6.5 min, SRc at 227.4 ℃, 16 min, and wSR at 180 ℃, 5 min (moistened for 50 min, with a yellow wine dosage of 18.2%). Correlation analysis shows that different degrees of processing of SR have distinguishable sensor response patterns: odor sensors S7 and S10 and taste sensors P6 and P10—P12 in fSR have a strong positive correlation with baicalin and wogonoside; In SRc and wSR, there is a strong negative correlation between multiple sensors and baicalin, while wogonin shows a strong positive correlation with multiple sensors SRc and a strong negative correlation with fSR. The electronic eye color values (L^*, a^*, b^*) are significantly correlated with the degree of processing (ΔE^*_ab > 1.5). Conclusion Optimizing the process is stable and feasible. The quality evaluation system based on electronic sensory technology can objectively distinguish the degree of processing, and the correlation between characteristics and components revealed provides theoretical basis and innovative methods for determining the endpoint of processing and quality control.

Objective To investigate clinical efficacy of Jiaotai Wan (JTW, 交泰丸), and selective serotonin reuptake inhibitors (SSRIs) in patients with depression, and to explore their underlying mechanisms. Methods Based on biological sample data from a previous multicenter, randomized, active-controlled parallel clinical trial, a total of 83 depression patients were divided into three groups: JTW group (n = 25), JTW combined with SSRIs group (n = 29), and SSRIs alone group (n = 29). A mixed linear model was used to analyze changes in short-chain fatty acids (SCFAs), neuroinflammatory markers [cyclooxygenase-2 (COX-2), prostaglandin E₂ (PGE₂)] and brain-derived neurotrophic factor (BDNF) before and after treatment in each group. Spearman correlation and structural equation modeling were used to explore the relationships between post-treatment biomarkers and clinical symptoms [Hamilton depression rating scale (HAMD) scores], and potential mediating pathways. Results HAMD scores decreased significantly from baseline in all three groups (P < 0.001), but there was no significant differences between the groups. The JTW group showed a significant increase in butyrate levels (P = 0.002) and maintained higher levels of acetate and propionate. The SSRIs group was associated with increased levels of isovalerate, isobutyrate, and hexanoate. After treatment, the JTW + SSRIs group showed significant increases in isobutyrate, isovalerate, and isohexanoate levels, and a significant decrease in acetate levels. The combined group had significantly higher BDNF levels than the other two groups (P < 0.05). The PGE₂ levels in the combined group were also higher than in the JTW group both at baseline and after treatment (P < 0.05). Correlation analysis showed a strong positive correlation between PGE₂ and BDNF in the combined group after treatment (r = 0.609, P < 0.001). In the SSRIs group, COX-2 was positively correlated with HAMD score (r = 0.451, P = 0.014). In the JTW group, isohexanoate was positively correlated with BDNF (r = 0.445, P = 0.026). Mediation analysis suggested a potential indirect effect in the combined group, where PGE₂ influenced HAMD scores through BDNF (indirect effect = −0.065, P = 0.093). Conclusion JTW alone, SSRIs alone and JTW combined with SSRIs all can effectively alleviate depressive symptoms. However, they showed different patterns in regulating gut SCFAs, neuroinflammation, and neurotrophic factors. JTW combined with SSRIs may modulate branched-chain fatty acid metabolism and promote a positive association between PGE₂ and BDNF, thereby creating a distinct pathway that differs from single therapies. These findings provide preliminary evidence for understanding the differential mechanisms of various antidepressant strategies, suggesting that personalized treatment should consider patients’ specific biological characteristics.

Objective To investigate the effects of calcination temperature on the phase composition and chemical constituents of Shijueming (Haliotidis Concha, HC), optimize its processing methodology, and conduct comparative analysis and health risk assessment of heavy metal content in HC and calcined HC. Methods Thermal effects during processing at different calcination temperatures were examined via thermogravimetric-differential thermal analysis (TG-DTA). Primary phase transformations were analyzed using X-ray diffraction (XRD), while compositional changes were assessed by Fourier transform infrared spectroscopy (FTIR) to preliminarily screen the key factor “calcination temperature” affecting HC processing. Simultaneously, the optimal processing parameters for HC were determined using the AHP-CRITIC mixed entropy method combined with orthogonal experiments, with CaCO₃ content, crispness, and color as evaluation criteria. Calcined HC were processed according to the optimized method. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to analyze 20 batches of HC and calcined HC for Pb, Cd, As, Hg, and Cu in 20 batches of HC and calcined calcined HC. Using HC powder as a reference, theoretical maximum limits for these five heavy metals and toxic elements were calculated. Daily exposure and target hazard quotient (THQ) were further assessed to evaluate health risks, providing a reference for quality and safety evaluation of HC. Results Preliminary screening of calcination temperatures indicated an optimal range of 400—600 ℃. Using the AHP-CRITIC mixed entropy method, the optimized calcination process for HC was determined as follows: Crush HC to a particle size < 1 cm, place in a muffle furnace, set the temperature to 600 ℃, and calcine for 90 min. After calcination, the organic matter content of HC decreased while calcium carbonate content increased. The calcined HC showed reduced levels of As and Hg, with minimal changes in Cu, Cd and Pb. Health risk assessment indicated that all 20 batches of HC and calcined HC posed no significant health hazards to humans. Notably, the As and Hg levels in the slices were significantly lower than those in the raw material (P < 0.05). Conclusion By integrating phase and compositional changes before and after processing, this study employed the AHP-CRITIC mixed entropy method to scientifically and comprehensively optimize the calcination process for HC. The screening results are scientifically reliable, providing new scientific evidence for quality management and clinical application of HC and calcined HC. Conducting health risk assessments of heavy metals and harmful elements in HC before and after processing provides reference for the safe clinical use of HC and other shell-derived Chinese medicinal materials.

Objective To study the non-saponin chemical constituents of the flower buds of Panax notoginseng and evaluate their antioxidant and anti-inflammatory activities. Methods The extraction was performed by refluxing with 65% aqueous ethanol, followed by successive liquid-liquid extraction with petroleum ether, ethyl acetate (EtOAc) and n-butanol. The compounds were isolated and purified using RP-18, silica gel, MCI gel CHP20P, Sephadex LH-20 column chromatography and semi-preparative liquid chromatography. Structural identification was carried out by comprehensive analysis of nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS), ultraviolet (UV) spectroscopy, and computational electronic circular dichroism (ECD) spectroscopy. Some purified compounds were evaluated for preliminary antioxidant activity and anti-inflammatory activity. Results A total of seven non-saponin components were isolated from the EtOAc fraction of P. notoginseng flower buds, including one isocoumarin (1), four simple phenols (2—5), and two loliolides (6, 7), were obtained from the EtOAc fraction. These were identified as isocoumarin F1 (1), ferulic acid (2), evofolin A (3), p-hydroxybenzoic acid (4), 4-hydroxybenzaldehyde (5), (＋)-epiloliolide (6), and (-)-loliolide (7), respectively. Conclusion All compounds (1—7) were isolated from P. notoginseng for the first time. Of which, compound 1 is a new isocoumarin and named isocoumarin F1, while compound 2 exhibited obvious DPPH radical scavenging ability.

Astragalus polysaccharides (APS) are the principal bioactive constituents of Huangqi (Astragali Radix), exhibiting diverse pharmacological activities. However, their clinical application is limited by challenges including high molecular weight, low solubility, and consequently poor bioavailability. Selenization modification has emerged as an effective strategy to improve the physicochemical properties and biological functions of APS, leading to the formation of selenized APS (Se-APS) and APS-selenium nanoparticles (APS-SeNPs). This review systematically summarizes the preparation methods, structural characteristics, biological activities, and structure-activity relationships of selenium-containing APS derivatives, and discusses their application prospects. Primary preparation techniques include biological transformation and chemical synthesis approaches. Following selenization, the resulting products demonstrate significantly improved solubility, stability, and bioavailability, and can form uniformly sized nanoparticles. Research indicates that selenium-containing APS derivatives exhibit superior pharmacological efficacy compared to native APS, including enhanced antioxidant, immunomodulatory, antitumor, and hepatoprotective activities. Furthermore, APS-SeNPs can serve as effective drug delivery carriers and show synergistic effects when combined with other bioactive compounds. Structure-activity relationship studies suggest that their bioactivity is closely associated with selenium content, molecular weight, and nanostructural attributes. Nevertheless, several challenges remain in this field, such as insufficient characterization of selenization sites and a lack of systematic toxicological evaluation. Future research should focus on optimizing preparation processes, strengthening safety assessments, and promoting clinical translation to advance their applications in the pharmaceutical and functional food industries.