Introduction Tongxinluo (TXL) capsule, composed of 12 Chinese herbal extracts, is indicated for the treatment of coronary heart disease. This study aimed to elucidate the chemical composition of TXL capsules and uncover their potential mechanisms against atherosclerosis through integrated component profiling, network pharmacology, and experimental validation. Methods TXL constituents were systematically characterized using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Network pharmacology was employed to predict therapeutic targets, followed by molecular docking. The anti-inflammatory activities of TXL were evaluated by measuring the inhibition of nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. The ability of TXL to reduce oxidative stress was assessed by the nuclear factor erythroid 2-related factor 2 (Nrf2) luciferase and intracellular reactive oxygen species (ROS) assays. Finally, the capacity of TXL extract to restore endothelial cell survival and function was evaluated in human endothelial EA.hy926 cells using cell migration and tube formation assays. Key signaling pathways were validated through Western blotting and immunofluorescence as guided by network pharmacology and molecular docking. Results Based on the 97 active ingredients identified in TXL, network pharmacology revealed 340 compound-disease intersection targets enriched in inflammation, oxidative stress, endothelial dysfunction, and lipid-related pathways with strong binding affinities between major TXL components and core atherosclerosis-related targets. TXL dose-dependently reduced LPS-induced NO, IL-6, TNF-α, and ROS levels. In endothelial cells, TXL attenuated H2O2-induced oxidative injury, restored viability, decreased ROS accumulation, and significantly enhanced migration and tube formation. The molecular mechanisms of TXL were associated with suppression of NF-κB p65 nuclear translocation and activation of the Nrf2-HO-1 axis. Discussion TXL restored endothelial survival and function, which were at least partly attributed to modulation of the NF-κB inflammatory pathway and activation of the Nrf2-HO-1 antioxidant axis to suppress inflammation and oxidative stress. These findings underscore TXL’s potential as a promising adjunctive therapy for the treatment of atherosclerosis.
Introduction Traditional Chinese medicine (TCM) nanoemulsion is regarded as an innovative application of nanotechnology in herbal formulations, which can enhance drug solubility, stability, and bioavailability by encapsulating active herbal components in nanoscale droplets. Methods A systematic literature search was performed in the following electronic databases: PubMed, ScienceDirect, Wiley, Springer, China National Knowledge Infrastructure, and Wanfang databases. The information retrieval covered the period from January 2016 to June 2026, and the keywords and their combinations were selected, including “nanoemulsion” “traditional Chinese medicine” “Chinese herbal medicine” “preparation method” “high-pressure homogenization” “ultrasonic emulsification” “phase inversion temperature” “self-emulsification” “formulation optimization” and “process parameters”. The search was limited to original research articles and systematic reviews published in the English or Chinese journals, which excluded the conference abstracts, case reports, patents, and publications. Reference lists of all included articles and relevant reviews were manually screened to identify additional eligible studies. The initial search yielded 487 records, and the full texts of potentially eligible articles were then retrieved and assessed; finally, 92 eligible references were included for systematic analysis. Results this paper systematically reviews the definition, classification, formation mechanisms, and the advantages of traditional Chinese TCM nanoemulsion, and also comprehensively summarizes the application of high-energy emulsification and low-energy emulsification methods. Furthermore, it analyzes the key factors affecting the preparation process, including components of the aqueous phase, oil phase, and emulsifiers. Discussion this review provides an important reference for formula optimization, process improvement and quality control of TCM nanoemulsion, and offers a critical support for accelerating the standardization and internationalization of TCM preparations.
Introduction Breast cancer remains the most frequently diagnosed malignancy and a leading cause of cancer-related mortality among women worldwide. Despite advances in targeted therapies, therapeutic resistance, recurrence, and metastasis remain major challenges. Increasing evidence identifies cellular plasticity as a key driver of these processes, while Traditional Chinese Medicine (TCM), with its multi-component and multi-target pharmacology, has emerged as a promising strategy to modulate these adaptive networks. Methods This review summarizes the molecular mechanisms of cellular plasticity in breast cancer and discusses how TCM-derived bioactive compounds regulate these processes. It also highlights the contributions of multi-omics technologies, systems pharmacology, network pharmacology, and artificial intelligence in advancing TCM research. Unlike previous reviews that primarily focus on individual TCM compounds or specific breast cancer pathways, this review integrates TCM interventions across formula, herb, extract, and compound levels with cellular plasticity, emerging technologies, and translational challenges. Results TCM-derived bioactive compounds, including curcumin, berberine, baicalein, ginsenosides, tanshinone IIA, triptolide, honokiol, emodin, and wogonin, inhibit epithelial–mesenchymal transition, cancer stemness, tumor dormancy, therapy-induced plasticity, metabolic and immune reprogramming, and metastatic evolution through coordinated regulation of multiple oncogenic signaling pathways. Discussion Cellular plasticity provides a unifying framework for understanding breast cancer progression and therapeutic resistance. By simultaneously targeting multiple adaptive processes, TCM represents a promising systems-based therapeutic strategy. Integration of multi-omics, artificial intelligence, and precision oncology will further facilitate the mechanistic validation and clinical translation of TCM for personalized breast cancer management.
Introduction Ischemic stroke causes substantial mortality and disability, and effective pharmacological neuroprotection remains limited. Naturally derived compounds with multi-target activities have gained increasing attention as potential adjunctive therapies. Among them, thymoquinone, a major active constituent of Nigella sativa, has emerged as a promising candidate in experimental ischemic stroke. This review evaluated the preclinical evidence on thymoquinone as a neuroprotective agent in experimental ischemic stroke. Methods This systematic review followed PRISMA guidelines. PubMed/MEDLINE, Scopus, ScienceDirect, and Europe PMC were searched up to December 30, 2025. Eligible studies investigated thymoquinone or Nigella sativa extract in animal models of ischemic stroke and reported neuroprotective outcomes. Data on animal model, intervention, outcomes, mechanisms, and methodological quality were extracted. Risk of bias was assessed using SYRCLE’s tool. Results From 872 records, 12 preclinical studies were included. Most studies used rodent ischemic stroke models, particularly MCAO. Thymoquinone improved neurological and motor outcomes, reduced infarct volume, brain edema, oxidative stress, inflammation, apoptosis, autophagy, and blood-brain barrier disruption, and promoted neuronal survival. The main mechanisms involved activation of Nrf2/HO-1 signaling, inhibition of TLR4/NF-κB pathways, modulation of microglial polarization, mitochondrial protection, and suppression of apoptotic signaling. Risk of bias assessment showed adequate reporting mainly for baseline characteristics, incomplete outcome data, and sequence generation, while several domains remained unclear. Discussion : Thymoquinone shows promising neuroprotective effects in experimental ischemic stroke through multi-target mechanisms. However, incomplete methodological reporting, heterogeneous models, variable dosing, and pharmacokinetic limitations may affect translational reliability. Further rigorous preclinical studies with optimized delivery systems are needed before clinical development.
Background Microneedle (MN)-mediated delivery has emerged as a promising strategy for improving the dermal and transdermal delivery of Traditional Chinese Medicine (TCM)-derived bioactive compounds. Although TCM possesses diverse pharmacological activities relevant to dermatological disorders, the therapeutic performance of many herbal constituents is limited by poor skin penetration, low aqueous solubility, chemical instability, and inadequate retention following conventional topical administration. This review provides a structured narrative synthesis of recent advances in MN-mediated delivery of TCM for dermatological applications, with emphasis on formulation strategies, therapeutic outcomes, emerging technologies, safety, and translational challenges. Methods A structured narrative literature review was conducted to identify and critically synthesize available evidence concerning microneedle-mediated delivery of Traditional Chinese Medicine (TCM) and TCM-derived bioactive compounds for dermatological applications. Literature was identified through searches of PubMed, Scopus, Web of Science, and Google Scholar for publications from January 2003 to March 2026. Relevant publications were screened for relevance to microneedle-mediated TCM delivery and critically evaluated according to study design, formulation characteristics, therapeutic outcomes, and translational relevance. Evidence was narratively synthesized according to microneedle type, fabrication materials, formulation and drug-loading strategies, therapeutic applications, safety considerations, and emerging technologies. Results The available evidence indicates that MN systems can overcome the stratum corneum barrier and enhance the local delivery, dermal deposition, and therapeutic performance of TCM-derived bioactive compounds. Dissolving, hydrogel-forming, coated, and nano-integrated MN systems have demonstrated promising results in preclinical models of inflammatory skin disorders, acne, pigmentation disorders, wound healing, and photoaging. Advanced approaches incorporating nanoparticles, nanocrystals, stimuli-responsive materials, and multifunctional systems may further improve controlled and targeted delivery. However, most evidence remains preclinical, and substantial challenges remain regarding formulation standardization, stability, reproducibility, manufacturing scale-up, safety evaluation, and regulatory translation. Discussion MN-mediated delivery represents a promising interface between TCM pharmacology and modern drug-delivery technology. Future research should prioritize standardized herbal preparations, mechanistically informed formulation design, reproducible manufacturing, comprehensive safety evaluation, and well-designed clinical studies to establish the therapeutic and translational value of MN–TCM systems in dermatological practice.
Cordyceps militaris is a traditional Chinese medicine (TCM) officially recognised as an herbal drug by the Chinese Pharmacopoeia since 1964, and it is increasingly consumed worldwide as a functional food, nutraceutical, and therapeutic adjunct in modern Chinese patent preparations. Its bioactive constituents chiefly cordycepin, adenosine, polysaccharides, and ergosterol have been studied extensively in preclinical models, yet consolidated human safety evidence remains scattered and is rarely synthesised independently of efficacy claims. Introduction To systematically evaluate the safety, tolerability, adverse events, treatment withdrawals, and laboratory safety outcomes of C. militaris preparations administered to humans, in the context of its established use in traditional Chinese medicine. Methods PubMed/MEDLINE and Scopus were searched and the review was conducted and reported in accordance with the PRISMA 2020 statement. Human clinical studies reporting any safety outcome for C. militaris were eligible. Risk of bias was assessed with the Cochrane RoB 2 tool, and certainty of evidence was rated using GRADE. Because comparative datasets were sparse and heterogeneous, quantitative pooling was pre-specified as exploratory. Results A total of 2482 records were identified (952 from PubMed/MEDLINE; 1530 from Scopus). After removal of 51 duplicates, 2431 records were screened and 2362 excluded; 61 full-text reports were assessed, of which five human primary studies were included in qualitative synthesis and four comparative studies were eligible for exploratory quantitative synthesis. Across studies, C. militaris was generally well tolerated. Treatment-emergent adverse events (TEAEs) were mild and infrequent; in the single study with extractable comparative counts the risk ratio for any TEAE was 1.40 (95% CI 0.44–4.45) and for treatment-related TEAE was 0.70 (95% CI 0.17–2.85). Severe and serious adverse events, reported together as a combined category in the source studies, were absent in all studies that reported them, producing double-zero event tables that were not estimable for pooling. Liver, renal, haematological, and metabolic markers showed no consistent toxic signal. Discussion Short-term administration of C. militaris preparations appears generally well tolerated in the populations studied, with no consistent signal of serious adverse events, hepatotoxicity, nephrotoxicity, or haematological toxicity. Certainty remains low to very low because of small samples, short durations, heterogeneous formulations, and incomplete adverse-event reporting. This aligns with, and extends, the therapeutic rationale underlying established TCM Cordyceps preparations such as Bailing and Jinshuibao capsules, though direct safety comparisons across preparations are not yet possible. Larger, longer, standardised randomised trials with outcome-specific risk-of-bias assessment are required to establish long-term safety, dose–response, and drug-interaction potential.
Background Bulbophyllum crassipes (known as duan er shi dou lan, 短耳石豆兰 in China), is an orchid species situated within the expansive and highly varied genus Bulbophyllum of the Orchidaceae family. It is native to tropical and subtropical regions of Asia, including parts of India, Bangladesh, Myanmar, Thailand, and southern China. This medicinally valued orchid was investigated for its neuropharmacological potential. The crude methanolic extract (ME) of its bulbs and derived fractions-n-hexane (NHF), chloroform (CLF), and aqueous (AQF)—were evaluated in Swiss albino mice. Methods Anxiolytic effects were assessed using the elevated plus maze, hole-board, light–dark box, and marble-burying tests; antidepressant activity via the forced swim and tail suspension tests; and sedative properties via the open field and hole-crossing tests. Results GC-MS analysis of the extract (ME) identified 86 bioactive compounds. At 400 mg/kg, ME demonstrated significant anxiolytic activity across all anxiety models. Both ME and CLF (400 mg/kg) markedly reduced immobility time in antidepressant tests, indicating mood-enhancing effects. The same dose also significantly decreased locomotor activity (p < 0.05 to p < 0.001), confirming sedative properties. In silico studies—including ADME, PASS prediction, and molecular docking—supported the experimental results. Key constituents showed strong binding affinities to neuropharmacological targets: MAO-A (PDB: 2Z5X), serotonin transporter (PDB: 5I6X), and GABAA receptor (PDB: 6 × 3X), aligning with observed anxiolytic, antidepressant, and sedative effects. Notably, three compounds—3,7,11-Trimethyl-dodeca-2,6,10-trienoic acid, Curdione, and Guanosine—showed particularly high and consistent docking scores across all three targets, indicating their potential as multi-target neuroactive medicines. Conclusion These findings validate the traditional use of B. crassipes and suggest its potential as a natural source for managing anxiety, depression, and sleep disorders.
Introduction Arthritis has emerged significant public health problem worldwide, characterized by the chronic joint inflammation, cartilage erosion, pain, and loss of movement. Diosmetin (DT), a bioactive flavonoid present in several Traditional Chinese Medicine (TCM) herbal preparation derived from Citrus species, has been traditionally associated with strong anti-inflammatory, antioxidant, and analgesic activity. The present study aimed to evaluate the therapeutic efficacy of DT in Complete Freund Adjuvant (CFA) induced arthritis model in Albino Wistar rats. The study hypothesized that DT may attenuate inflammatory and oxidative alterations associated with experimental arthritis through multi-target anti-inflammatory and antioxidant mechanism. Method Arthritis is successfully induced using CFA and animal were categorized into five groups (n = 6 each group): Normal Control, Arthritic Control, Arthritic + DT (25 mg/kg), Arthritic + DT (50 mg/kg), and Arthritic + Methotrexate (MTX) (2 mg/kg/weekly, i.p.) as a positive control. All treatments were orally given for 21 days, except methotrexate. Various parameters including, clinical arthritis scores, paw volume, pain thresholds, oxidative stress parameters (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH], pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), histopathology, and radiographic were assessed. Results DT significantly diminished the arthritic scores, paw oedema, and pain behaviour in comparison with the arthritic untreated group (p < 0.05). A marked decrease in MDA and a significant increase in SOD and GSH activity were observed in diosmetin-treated groups. Additionally, DT significantly suppressed pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. Histological study confirmed that preservation of cartilage architecture with reduced synovial inflammation, and radiographic findings showed reduced joint space narrowing and bone erosion. Conclusion In conclusion, DT exhibited significant anti-arthritic, anti-inflammatory, and antioxidant effect in a CFA induced arthritis model. These findings suggest its potential as a promising therapeutic cargo for arthritis management and supports its pharmacological relevance in TCM-associated therapeutic applications.
Background Traditional Chinese Medicine (TCM) is being increasingly integrated with artificial intelligence (AI), creating new opportunities for data-driven research, intelligent diagnosis, drug discovery, and the modernization of traditional healthcare systems. This review summarizes recent advances in AI-enabled TCM research and highlights current challenges and future directions. Methods A structured literature search was conducted using PubMed, Google Scholar, and SpringerLink for studies published between January 2010 and January 2025. Boolean search strategies combined terms related to Traditional Chinese Medicine, machine learning, deep learning, natural language processing, knowledge graphs, and large language models. Eligible English- and Chinese-language publications relevant to AI applications in TCM were screened and qualitatively synthesized. Results The retrieved literature demonstrated rapid growth of AI applications across four major domains: multiscale TCM data resources, AI-driven research and development, AI-assisted diagnosis and treatment and large language models. AI approaches have been applied to syndrome differentiation, tongue and pulse analysis, prescription recommendation, quality control, network pharmacology, target prediction, and multimodal knowledge integration. However, limitations remain regarding data heterogeneity, standardization, external validation, interpretability, privacy, and clinical safety. Conclusion AI has strong potential to accelerate the modernization and global translation of TCM, but successful implementation will require standardized datasets, explainable models, prospective clinical validation, robust governance, and integration with existing healthcare systems. Future progress is expected through multimodal learning, retrieval-augmented generation, and clinician-centered decision-support frameworks.
Introduction Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by high rates of recurrence, metastasis, and limited targeted therapeutic options. Curcuma longa (turmeric; 姜黄, Jiang Huang), a medicinal plant widely used in traditional Chinese medicine (TCM), contains bioactive constituents with reported anticancer activities. Turmeric-derived exosome-like nanovesicles (TDENs) have recently attracted interest as natural nanocarriers; however, their molecular mechanisms in TNBC remain poorly understood. This study investigated the anti-TNBC mechanisms of TDENs using an integrated network pharmacology and computational approach. Methods TDENs were isolated by sequential centrifugation and characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The metabolite cargo was profiled by LC-HRMS, and the identified metabolites were analyzed through network pharmacology to determine potential TNBC-related targets and pathways. Molecular docking and molecular dynamics simulations were performed to evaluate ligand-protein interactions and complex stability. Results DLS and TEM demonstrated physicochemical characteristics consistent with turmeric-derived exosome-like nanovesicles (TDENs), while LC-HRMS identified 24 putatively annotated metabolites. Network pharmacology revealed 185 overlapping targets between TDEN-derived compounds and TNBC-associated genes, with EGFR identified as a key hub target. GO and KEGG enrichment analyses indicated significant involvement of the PI3K-AKT and MAPK signaling pathways. Molecular docking identified cyclobisdemethoxycurcumin as the top-ranked ligand against EGFR and revealed favorable interactions with AKT and RAF, while molecular dynamics simulations confirmed the stability of the selected ligand-protein complexes. Discussion The findings suggest that TDEN-derived metabolites may modulate TNBC-associated molecular networks through coordinated interactions with components of the EGFR signalling axis. The identified involvement of EGFR, AKT, and RAF, together with enrichment of the PI3K-AKT and MAPK pathways, provides a mechanistic framework for understanding the potential biological effects of TDEN-derived metabolites in TNBC and supports future in vitro and in vivo validation of these computational findings.
Background: Cordycepin (3′-deoxyadenosine), the principal bioactive constituent of Cordyceps militaris and Ophiocordyceps sinensis - entomopathogenic fungi long valued in traditional Chinese medicine (TCM) as the tonic DongChongXiaCao - was isolated in 1950, making it among the earliest nucleoside analogs identified in the scientific literature. It has since accumulated seven decades of anticancer evidence spanning multiple hallmarks of cancer. Yet no cordycepin-based therapeutic reached regulatory approval until a single recurring pharmacokinetic obstacle was isolated and directly addressed. Objective: This review reorganizes the cordycepin anticancer literature around what is termed here the cordycepin translational bottleneck - rapid inactivation by adenosine deaminase (ADA), dependence on Human equilibrative nucleoside transporter 1 (hENT1) for cellular uptake, and rate-limiting intracellular kinase phosphorylation - and traces the successive strategies developed to resolve it. Methods: Literature was identified through structured searches of PubMed, Scopus, and Web of Science (1950-2026) using terms combining cordycepin, Cordyceps militaris, and related pharmacological and clinical terms, supplemented by targeted searches for comparator nucleoside-analog oncology drugs. Findings: Four overlapping resolution strategies are traced chronologically: ADA-inhibitor co-administration, ADA-resistant structural analogs, nanocarrier-based delivery, and phosphoramidate (ProTide) prodrug chemistry. The last produced NUC-7738 (fosdesdenosine sipalabenamide), which overcomes all three components of the bottleneck simultaneously - ADA-mediated deamination, hENT1 transporter dependence, and rate-limiting intracellular kinase phosphorylation - by delivering cordycepin monophosphate directly into the intracellular space, bypassing the rate-limiting first kinase step that constrains all unmodified nucleoside analogues and has progressed through Phase I/II trials, with evidence of restored anti-tumor immunity when combined with pembrolizumab in PD-1-resistant melanoma. Comparison with four approved nucleoside-analog oncology drugs situates this resolution among precedented and novel translational strategies. Conclusion: Although cordycepin was among the earliest nucleoside analogs to be identified, it took nearly seventy years to reach a human oncology trial, a far slower path than another TCM-derived compound artemisinin, that reached patients within the year of its isolation. The translational bottleneck, not the underlying biology, was the central barrier to cordycepin's clinical development; engineering around it via phosphoramidate prodrug (ProTide) chemistry overcomes all three components simultaneously - ADA-mediated deamination, hENT1 transporter dependence, and rate-limiting intracellular kinase phosphorylation - producing the field's first cordycepin derivative to reach human oncology trials.
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, cartilage destruction, and progressive bone erosion. Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, contributes to RA pathogenesis by linking oxidative stress, inflammation, and immune dysregulation within the joint microenvironment. Owing to its multi-component and multi-target properties, traditional Chinese medicine (TCM) represents a promising strategy for modulating ferroptosis-related pathways. In TCM theory, RA is categorized as ''Bi syndrome'' and treated with herbs that dispel wind-dampness, promote blood circulation, and relieve pain. This review summarizes current evidence on ferroptosis mechanisms and the ferroptosis-modulating potential of TCM in RA. Methods: This review examines current evidence on ferroptosis-mediated mechanisms in RA and the regulatory effects of TCM interventions. Literature was retrieved from PubMed, Web of Science and CNKI up to December 2025. Eligible studies included cellular, animal, and clinical investigations addressing ferroptosis-related processes, including iron metabolism dysregulation, lipid peroxidation, oxidative stress imbalance, and antioxidant defense dysfunction, as well as TCM-based interventions in RA or related inflammatory diseases. Results: Accumulating evidence indicates that ferroptosis contributes to RA progression through dysregulation of iron metabolism, lipid peroxidation, and antioxidant defense systems. A variety of bioactive compounds from anti-rheumatic TCM herbs such as saikosaponins, icariin, baicalin, and sinomenine have demonstrated the ability to modulate ferroptosis-related pathways and alleviate joint inflammation and damage. In addition, classical TCM formulas and emerging nano-TCM delivery systems exhibit multi-component and multi-target properties that may enhance therapeutic efficacy by regulating ferroptosis and associated signaling pathways. Discussion: TCM interventions offer promising strategies for RA by targeting ferroptosis through multi-level mechanisms, consistent with their traditional use in treating “Bi syndrome.” However, further studies are required to clarify the synergistic effects of complex herbal formulas, identify reliable ferroptosis-related biomarkers, and evaluate the safety and clinical applicability of these interventions. Integrating traditional medicinal knowledge with modern pharmacological approaches may facilitate the development of novel ferroptosis-targeted therapies for RA.
Introduction Eleutherococcus giraldii (Harms) Nakai, commonly known as Hong-mao-wu-jia, is an ethnomedicinal plant whose stem bark is used within the broader Wu-jia-pi tradition. In traditional Chinese medicine and regional materia medica, its stem bark, regionally referred to as Chuan-wu-jia-pi, is used to dispel wind-dampness, reduce swelling, and strengthen tendons and bones, particularly for rheumatic disorders characterized by joint pain and limb weakness. Representative preparations include decoctions, medicated wine, and pills. However, because Wu-jia-pi may refer to materials derived from different botanical sources and medicinal parts, source attribution and evidence interpretation remain challenging. This review critically evaluates the ethnomedicinal relevance, authentication, phytochemistry, pharmacology, quality evaluation, and safety of E. giraldii, with emphasis on evidence strength and translational limitations. Methods PubMed, Web of Science Core Collection, Google Scholar, CNKI, and Wanfang were searched from inception to 25 March 2026. After duplicate removal, screening, and eligibility assessment, 111 sources were included for narrative synthesis. Evidence was interpreted by botanical source, medicinal part, test material, extraction or fractionation procedure, chemical characterization, dose or concentration, model, administration or exposure route, positive control, endpoint, mechanistic validation, safety relevance, and reporting completeness. Results E. giraldii contains polysaccharides, terpenoids, phenylpropanoids, flavonoids, fatty acids, nucleobases, nucleosides, and other minor constituents, with marked variation among plant parts and preparations. Anti-inflammatory, analgesic, and immunomodulatory effects are supported by relatively consistent preclinical evidence, whereas hepatoprotective, cardiovascular, neuroactive, antiviral, antitumor, anti-hypoxic, and anti-fatigue activities remain preliminary or heterogeneous. Current quality evaluation relies mainly on botanical authentication, marker assays, and chromatographic fingerprinting, but marker-efficacy relationships remain insufficiently defined. Evidence is also insufficient for conclusions on chronic, genotoxic, reproductive, interaction-related, and preparation-specific safety. Discussion The current evidence is limited by inconsistent authentication, incomplete medicinal-part and dose reporting, heterogeneous preparations, limited mechanistic validation, and inadequate safety assessment. Future studies should use authenticated materials, medicinal-part-specific designs, standardized characterization, mechanistic pharmacology, marker-efficacy correlation, and systematic toxicological evaluation.
Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 30% of the global population. Accumulating evidence indicates that ferroptosis is implicated in the transition from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), representing a potential therapeutic target. This review aims to elucidate the role of ferroptosis in MASLD progression and systematically evaluate studies demonstrating that traditional Chinese medicine (TCM) ameliorate MASLD through ferroptosis modulation, thereby providing a foundation for future research. Methods A narrative synthesis of ferroptosis and its role in MASLD progression was combined with a PRISMA 2020-guided systematic review of TCM interventions targeting ferroptosis for MASLD treatment. Searches were conducted in PubMed and CNKI; TCM studies were screened against predefined inclusion and exclusion criteria by two independent reviewers. Results MASLD-associated hepatic steatosis predisposes the liver to ferroptosis. Beyond mitochondria, other organelles contribute to ferroptosis. The interplay among distinct hepatic cell types promotes a self-amplifying "ferroptosis–inflammation–fibrosis" circuit. Beyond glutathione peroxidase 4 (GPX4), parallel defense systems exert ferroptosis-suppressive functions. Systematic analysis of 36 TCM-based studies revealed dose-dependency with good in vivo–in vitro concordance in the majority of studies; however, meaningful structure–activity relationship (SAR) analysis was feasible only for flavonoids. Notable limitations include insufficient standardization of TCM formulas/herbs and suboptimal dose design. Conclusion Ferroptosis represents a potential mechanistic link in MASLD progression. TCM demonstrated promising potential in improving MASLD through the regulation of ferroptosis. However, all studies remain at the preclinical stage and carry limitations; further investigations are indispensable to translate these findings into clinical practice.
Introduction: Dry eye disease (DED) is characterized by persistent disruption of tear film homeostasis, and durable restoration remains challenging. Traditional Chinese medicine (TCM) monomers are chemically defined bioactive compounds that may modulate multiple pathogenic processes. This review evaluates their pharmacological actions and translational limitations, using tear film stability as the central functional framework. Methods: PubMed/MEDLINE, Web of Science Core Collection, and Scopus were searched from inception to July 28, 2026 for DED and tear-film phenotypes, TCM monomers, mechanisms, and functional outcomes. Direct evidence was restricted to single chemically characterized compounds. Extracts, polysaccharides, total saponin or flavonoid fractions, and multicomponent preparations were not considered direct monomer evidence. In vitro, animal, and clinical findings were distinguished; non-ocular evidence was used only to generate hypotheses. Results: Preclinical studies suggest that selected TCM monomers may attenuate inflammation, oxidative stress and ferroptosis, preserve epithelial barrier integrity, and support mucin-related function. Models showed improvements in tear breakup time, tear secretion, corneal staining, and epithelial protection. However, direct evidence for regulation of meibomian gland lipid metabolism by individual monomers remains sparse and largely indirect, and human clinical evidence is limited. Safety evidence is mainly indirect; ocular pharmacokinetics and long-term topical safety remain insufficiently characterized. Discussion: TCM monomers may provide a multi-pathway approach to preserving ocular surface wettability, epithelial integrity, and tear film continuity. Nevertheless, proposed effects on meibomian lipid metabolism and population-specific safety signals should be regarded as hypothesis-generating until they are confirmed in standardized monomer-level models and clinical studies. Translation will require standardized tear-film endpoints, pathway-specific validation, rigorous quality control, ocular pharmacokinetic characterization, long-term safety assessment, and biocompatible ophthalmic formulations.
Introduction In Traditional Chinese Medicine, Agrimonia pilosa (AP) is widely consumed as tea decoction and has traditionally been used for its hemostatic, astringent, and anti-swelling properties. Agrimonolide (AG), a major coumarin isolated from A. pilosa extract (APE), has demonstrated anti-inflammatory activity in an in vitro assay, although its efficacy in in vivo models remains unexplored. Furthermore, the wound healing activity of both APE and AG has not yet been systematically investigated. Therefore, the current study aimed to investigate the anti-inflammatory and wound healing effects of APE and AG in in vivo models, supported by in silico molecular docking analysis. Methods AG was isolated and characterized from APE by column chromatography. Both APE and AG were formulated as topical gels and evaluated for acute dermal toxicity. Anti-inflammatory efficacy was evaluated in carrageenan (CAR)-induced acute and Complete Freund's Adjuvant (CFA)-induced chronic inflammation models, and wound healing activity was evaluated using an excision-induced wound model. Biochemical markers for inflammation (TNF-α, IL-6), oxidative stress (LPO, SOD, GSH), and extracellular matrix components (hydroxyproline, hexosamine, protein) were examined, alongside histopathology. The docking interactions of AG with GSK-3, TNF-α, and IL-6 protein were evaluated. Results Topical application of APE (2000 mg/kg) and AG (200 mg/kg) caused minimal irritation in rats, with no behavioral abnormalities or death. Treatment with APE-Gel (10%) and AG-Gel (0.5%), when compared with the negative control, effectively reduced (p < 0.05) CAR and CFA-induced paw edema by 37–40% and 24–27%, respectively. Furthermore, APE-Gel (10%) and AG-Gel (0.5%) treatment accelerated wound closure by >85% by day 21. APE and AG treatment, in contrast to the negative control showed increased (p < 0.05) hydroxyproline, protein, and antioxidant levels (SOD, GSH), while reducing (p < 0.05) LPO, TNF-α, and IL-6 levels. Histological findings confirmed protection against inflammation and wound-induced tissue damage. In silico molecular docking predicted binding energies of −52.34, −59.36, and −71.86 kcal/mol for AG against GSK-3, TNF-α, and IL-6, respectively, showing more favorable binding than the reference drugs toward GSK-3 and TNF-α, but not IL-6. Conclusion APE and AG exhibited significant anti-inflammatory and wound healing activities by modulating cytokine release, oxidative stress, and enhancing collagen production. Nevertheless, these findings are based on preclinical models, and further mechanistic and clinical studies are required to validate their therapeutic potential.
Introduction Si-Miao-Yong-An decoction (SMYAD), a classical traditional Chinese medicine (TCM) formulation, has served for centuries as a cornerstone therapy for vascular pathologies including gangrene and vasculitis, and continues to demonstrate extensive clinical utility in treating cardiovascular and metabolic diseases. This review comprehensively synthesizes current research progress regarding SMYAD’s phytochemical composition, structural characteristics, migratory constituents, quality control measures, pharmacokinetic properties, pharmacological mechanisms, and clinical applications. Methods A comprehensive literature search was conducted through July 10, 2026 using PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI), with all studies meeting pre-established inclusion criteria retrieved, critically evaluated, and synthesized through thematic analysis. Results The review reveals that SMYAD demonstrates robust clinical efficacy across multiple therapeutic domains, with documented modified formulations expanding its therapeutic reach beyond the traditional decoction form to include various pharmaceutical preparations. Researchers have identified and preliminarily characterized numerous chemical constituents, with pharmacokinetic profiles established for select bioactive compounds. Clinical applications span internal medicine, surgery, and dermatology, addressing a wide spectrum of vascular-related disorders. Mechanistically, SMYAD exerts protective effects against vascular diseases through multi-targeted regulation of lipid metabolism, inflammatory responses, oxidative stress, autophagy, and angiogenesis. The formula modulates key signaling pathways including NF-κB, NLRP3, Nrf2/ARE, VEGF/VEGFR, and HIF-1α, while influencing macrophage polarization, cell death regulation, endothelial protection, and cholesterol transport. Discussion Despite these advances, several critical gaps remain that warrant future investigation: (1) development of modernized quality control standards meeting contemporary pharmaceutical requirements, (2) further elucidation of molecular mechanisms linking individual components to specific therapeutic effects, (3) validation of clinical efficacy and safety through rigorous randomized controlled trials, and (4) advancement of multi-formulation development to optimize therapeutic delivery and patient compliance. This comprehensive analysis provides a theoretical foundation for the continued research and clinical application of SMYAD in treating cardiovascular and metabolic diseases.
Introduction Cardiac hypertrophy is a major precursor of heart failure and is closely associated with mitochondrial dysfunction. Although andrographolide has demonstrated cardioprotective properties, its effects on mitochondrial quality control (MQC) during hypertensive cardiac remodelling remain unclear. This study investigated whether andrographolide attenuates salt-sensitive cardiac hypertrophy by modulating MQC and apoptosis-associated signalling in a uninephrectomy-deoxycorticosterone acetate-salt (UNX-DOCA-salt) rat model. Material and methods Male Sprague-Dawley rats subjected to the UNX-DOCA-salt model were treated with andrographolide or spironolactone. Cardiac hypertrophy was assessed by cardiac weight, cardiac weight-to-body weight ratio, and cardiomyocyte cross-sectional area. Mitochondrial function was evaluated by succinate dehydrogenase activity, mitochondrial calcium concentration, and mitochondrial DNA copy number, while the expression of hypertrophy-, MQC-, and apoptosis-related genes was quantified by RT-qPCR. Partial least squares regression (PLS-R), correlation analysis, molecular docking, and MM/GB(PB)SA were performed to identify and computationally validate key molecular determinants. Results UNX-DOCA-salt induced marked cardiac hypertrophy, mitochondrial dysfunction, and upregulation of DRP1, PINK1, PGC-1α, TFAM, p53, and BNP. Among the tested doses, andrographolide at 30 mg/kg body weight more consistently restored structural, mitochondrial, and molecular alterations than 60 mg/kg body weight. Multivariate analysis identified DRP1 as the principal molecular determinant associated with hypertrophic remodeling, whereas molecular docking and MM/GB(PB)SA demonstrated energetically favorable interactions of andrographolide within the DRP1 GTPase-binding region. Discussion These findings suggest that andrographolide attenuates salt-sensitive cardiac hypertrophy, at least in part, through modulation of mitochondrial homeostasis. DRP1-mediated mitochondrial dynamics may represent a promising therapeutic target underlying the cardioprotective effects of andrographolide in hypertensive cardiac remodeling.
Background Rutin (芦丁) and L-theanine(茶氨酸) are notable bioactive compounds employed in traditional Chinese medicine (TCM) for their diverse therapeutic effects. With the increasing global burden of Diabetes mellitus, the concurrent use of herbal supplements along with conventional therapy has become a routine practice. The present study evaluated the pharmacokinetic–pharmacodynamic interactions of Rutin and L-theanine with Metformin in preclinical models to provide preliminary translational insights into herb–drug interactions in diabetes management. Methods Male wistar rats weighing about 160–230 g were included in the study. Intraperitoneal administration of a single dose of Nicotinamide (100 mg/kg) and Streptozotocin (50 mg/kg) induced Type 2 diabetes. The normal and diabetic rats were treated with 100 mg/kg dose of Metformin alone and in combination with 20 mg/kg dose of Rutin or 50 mg/kg dose of L-theanine for an experimental period of 21 days. Results Diabetes impeded Metformin absorption, while the simultaneous administration of a single dose of Rutin or L-theanine partially altered its pharmacokinetic profile in diabetic rats. Rutin diminished systemic exposure despite improved absorption kinetics, whereas L-theanine augmented the absorption rate without influencing systemic exposure in diabetic rats. The repeated co-administration of Rutin or L-theanine did not result in significant pharmacokinetic alterations in normal rats; however, in diabetic rats, elevated Cmax and systemic exposure while reducing Tmax and clearance, with L-theanine yielding the most substantial increase in Metformin exposure. Conclusion Rutin and L-theanine differentially altered the pharmacokinetic profile of Metformin following repeated dosing, providing preliminary preclinical evidence of potential herb–drug interactions. Further mechanistic and clinical investigations are required to establish their underlying mechanisms and translational relevance.
