The forkhead box protein 3 (FoxP3)/regulatory T cell (Treg) axis is a key regulatory network that maintains peripheral immune tolerance and immune homeostasis, and its functional imbalance is closely associated with immune-related diseases, including autoimmune diseases, cancer, and allergic diseases. Traditional Chinese medicine (TCM), with its characteristics of multi-components, multi-targets, and multi-pathways, shows unique advantages in regulating the FoxP3/Treg axis. This article systematically reviews the multidimensional mechanisms by which TCM and its active components regulate FoxP3 expression and Treg cell differentiation, stability, and immunosuppressive functions. These mechanisms include direct regulation of key signaling pathways and cytokine networks, indirect influence on the gut microbiota-immune axis, and mediation of FoxP3 epigenetic modifications. It also summarizes the characteristics of bidirectional regulation, treating different diseases with the same method and treating the same disease with different methods observed in immune regulation. This provides important reference for the precise and modern application of TCM in treatment of immune-related diseases.

Huangjing (Polygonati Rhizoma) is a medicinal and edible herb whose quality is primarily determined by its intrinsic medicinal properties, mainly characterized by polysaccharides and saponins. However, the content and composition of these bioactive constituents are highly susceptible to variations in germplasm, ecological conditions, and processing methods, leading to significant fluctuations in commercial product quality—a critical bottleneck impeding the standardized development of the industry. Traditional research has predominantly focused on the apparent effects of individual ecological or agronomic factors, lacking a holistic analysis of the complex system governing quality formation. This review focuses on the intrinsic medicinal quality of Polygonati Rhizoma and constructs a systematic theoretical framework of “genetic-environment-management” multifactorial interactions to elucidate the multidimensional regulatory network underlying its quality formation. The article comprehensively reviews and analyzes the synergistic regulatory mechanisms of various factors and their interactions on quality traits from three dimensions: intrinsic genetic basis (germplasm resources and metabolic regulatory networks), extrinsic environmental regulation (climatic factors and rhizosphere microecological interactions), and anthropogenic production interventions (precision cultivation and post-harvest processing). On this basis, we propose that future research should prioritize systems biology analysis through multi-omics integration, intelligent and precise management across the entire industrial chain, modernization and value-added transformation of processing technologies, and the establishment of a whole-process quality standard system. This review provides an integrated theoretical framework for understanding the formation mechanism of the geo-authentic medicinal quality of Polygonati Rhizoma and offers a theoretical foundation for guiding its standardized production and high-quality industrial development.

Objective To investigate the mechanism by which tetrandrine regulates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway to induce ferroptosis in breast cancer cells based on peroxiredoxin 1 (PRDX1). Methods Human breast cancer MCF-7 cells transfected with PRDX1 siRNA were treated with tetrandrine to examine its effects on cell proliferation, apoptosis, migration and invasion. The levels of malondialdehyde (MDA), Fe²⁺, intracellular and mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential, and mitochondrial membrane permeability were measured. Western blotting and qRT-PCR were used to detect the expressions of voltage-dependent anion channel 1 (VDAC1), p53, PI3K/Akt/GSK-3β signaling pathway and nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway related proteins and genes. Results Tetrandrine dose-dependently inhibited MCF-7 cell proliferation, migration and invasion while inducing apoptosis (P < 0.01), increased intracellular and mitochondrial ROS, MDA and Fe²⁺ levels (P < 0.01), aggravated lipid peroxidation, reduced mitochondrial membrane potential (P < 0.01), enhanced mitochondrial membrane permeability (P < 0.01), upregulated HO-1, p53, GSK-3β and VDAC1 expressions (P < 0.01), downregulated Nrf2, PI3K, p-PI3K, Akt and p-Akt expressions (P < 0.01). Knockdown of PRDX1 gene significantly amplified these effects of tetrandrine (P < 0.01). Conclusion Tetrandrine induces mitochondria-associated ferroptosis in MCF-7 cells via PI3K/Akt/GSK-3β signaling pathway, with PRDX1 playing a critical regulatory role.

Objective To explore the therapeutic effect and related mechanism of citronellol on methicillin-resistant Staphylococcus aureus (MRSA)-induced skin infections in mice via NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway. Methods The minimum inhibitory concentration (MIC) of citronellol against standard MRSA strains was determined using the microbroth dilution method. A full-thickness skin MRSA infection model was established in female C57BL/6 mice, control group, model group, positive control (2% mupirocin) group, citronellol low-, medium- and high-dose (0.75%, 1.50%, 3.00% citronellol gel) groups were set up. Local administration was performed for 7 d. Wound healing rates were dynamically monitored, hematoxylin-eosin (HE) staining was used to observe histopathological changes in skin tissues, and ELISA was used to detect levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in skin tissues. Masson staining was used to observe collagen fiber deposition in skin tissues. RNA-seq transcriptome sequencing, qRT-PCR and Western blotting were employed to analyze the expressions of NLRP3 inflammasome pathway-related genes and proteins in skin tissues, while molecular docking was used to predict the binding affinity of citronellol to relevant inflammatory targets. The lactate dehydrogenase (LDH) release assay was used to evaluate the effect of citronellol on pyroptosis in MRSA-infected immortalized keratinocytes. Results Citronellol exhibited significant antibacterial activity against MRSA, with an MIC ranging from 0.312 5—0.625 0 mg/mL. In vivo experiments revealed that compared with model group, citronellol significantly accelerated wound healing, reduced inflammatory cell infiltration and tissue edema, decreased IL-1β and TNF-α levels in skin tissues (P < 0.05, 0.01, 0.001), markedly increased collagen fiber deposition at wound sites (P < 0.05, 0.01), and inhibited the activation of NLRP3 inflammasome-cell pyroptosis pathway (P < 0.05, 0.01, 0.001). Molecular docking results indicated that citronellol could bind to target proteins such as IL-1β. In vitro experiments demonstrated that citronellol significantly suppressed LDH release in MRSA-infected HaCaT cells (P < 0.05, 0.01). Conclusion Citronellol exerts significant antibacterial, anti-inflammatory and wound repair-promoting effects on MRSA-induced skin infections in mice. Its mechanism may be related to inhibiting NLRP3 inflammasome-cell pyroptosis pathway, reducing the release of pro-inflammatory cytokines, improving the local immune microenvironment, and promoting collagen deposition.

Natural product hydrogels, self-assembled from active components of traditional Chinese medicine (TCM) such as steroids, triterpenoids, flavonoids, alkaloids, and quinones, represent a significant class of functional systems. Leveraging their intrinsic amphiphilic structures, these compounds spontaneously form stable three-dimensional networks through intermolecular interactions including hydrophobic effects, π-π stacking, hydrogen bonding, and coordination bonds. These hydrogels possess the core “drug-carrier integration” feature, offering unique advantages for drug delivery and disease therapy. Key properties such as bioadhesion, targeted localization, stimuli-responsive release, and in situ gelation enable precise drug delivery and enhanced therapeutic efficacy. However, significant challenges persist in this field: the self-assembly pathways and dynamic evolution mechanisms of many natural products remain incompletely elucidated, hindering the precise construction of functional materials. Furthermore, existing evaluation systems often fail to comprehensively reflect their in vivo pharmacological effects, resulting in a notable lag in clinical translation. Future research should, therefore, prioritize the systematic analysis of multi-level self-assembly mechanisms. This involves exploring the intrinsic relationships between molecular structure, assembly kinetics, and macroscopic properties, alongside their applications in intelligent drug delivery and therapy. Such efforts are expected to provide a theoretical basis for the rational design of natural product-based functional materials and to inform new directions for developing innovative TCM formulations and precision medicine.

Objective To conduct a visual analysis of hotspots and development trends in Curcumae Radix research domestically and internationally using bibliometric software CiteSpace and VOSviewer, and provide a reference for in-depth research and application of Curcumae Radix. Methods The China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Platform, Web of Science (WOS) Core Collection, and PubMed databases were searched as data sources. The search period was set from January 1, 2016 to December 12, 2025. Analyses of publication volume, authors, and keywords were performed on the selected literature using CiteSpace6.4.R1 and VOSviewer1.6.20 softwares. Results A total of 1 354 Chinese literature and 77 English literature were included. Shi Zhenggang was identified as the core author of Chinese publications with 21 papers, while Ji De was the core author of English publications with six papers. Chinese research has formed a bidirectional knowledge network of “clinical experience-computational mechanism” represented by “data mining” and “network pharmacology”. English research focuses on “Curcumae Radix” and “molecular docking”, demonstrating an in-depth path of “computational prediction-disease focus”. The research hotspots are rapidly evolving from early-stage clinical efficacy observation to data-driven and computational pharmacological mechanistic elucidation. Conclusion Research on Curcumae Radix has evolved from simple efficacy observation into a systematic exploration that equally emphasizes “clinical problems” and “mechanistic elucidation”, while deeply integrating computational simulation and systems biology methods. Future efforts should focus on establishing a closed-loop research system of “computational prediction-experimental verification”, promoting high-quality evidence-based transformation, thereby driving the transformation and upgrading of this field toward precision medicine and modernized pharmacology.

Objective To conduct a bibliometric analysis of the relevant literature on traditional Chinese medicine with nourishing-yin properties for tumor prevention and treatment published both domestically and internationally over the past 20 years, with the intention of providing references for the pharmacological effects and scientific connotations of such traditional Chinese medicine in tumor prevention and treatment. Methods The relevant literature was obtained from the databases of China National Knowledge Infrastructure (CNKI), Wanfang Data, and Web of Science (WOS). Using bibliometrics and visualization research tools such as NoteExpress, CiteSpace, VOSviewer, and Gephi, the publication volume, countries, institutions, authors, and keywords of the selected literature were analyzed to form visualization results and analyze the current research status, hotspots, and trends. Results The analysis of publication volume shows that the research on yin-nourishing traditional Chinese medicine in tumor prevention and treatment has been increasing year by year. Currently, Chinese literature is the main body of research literature in this field. Maidong (Ophiopogonis Radix), Shihu (Dendrobii Caulis), and Gouqizi (Lycii Fructus) are the most frequently studied yin-nourishing traditional Chinese medicines in this field. The analysis of the countries and institutions that published papers indicates that the country with the most research publications in this field is China, and the dominant forces are Chinese medical colleges and hospital units. The analysis of authors’ publications shows that there is no core author group formed between domestic and international authors, and the research force in this field presents a diversified situation. The keyword analysis indicates that the research in this field mainly focuses on lung cancer, active ingredients, pharmacological effects, etc., while the medication pattern, data mining, mechanism of action, cell cycle regulation, and Lycium barbarum polysaccharides are the research hotspots in recent years. Conclusion Research on the prevention and treatment of tumors with yin-nourishing traditional Chinese medicine is still in an upward development stage at present. The research focus is on the study of the material basis and mechanism of action of yin-nourishing traditional Chinese medicines in preventing and treating tumors, as well as the research on clinical application experience and innovation in research methods.

Objective To investigate the therapeutic effect of icariin on diabetic kidney disease (DKD) and elucidate its molecular mechanism from the perspective of renal inflammatory response and related inflammatory signaling pathways. Methods A DKD model was established using C57BL/KsJ db/db mice, with age-matched db/m mice on the same genetic background serving as control group. The db/db mice were randomly divided into model group, dapagliflozin (1.6 mg/kg) group, icariin high-, medium-, low-dose (120, 60, 30 mg/kg) groups, with 10 mice in each group. Drugs were given for continuously intervention over four weeks, biochemical parameters including body weight, blood glucose, urinary protein, blood lipids and serum creatinine were measured. Renal pathological changes were observed using hematoxylin-eosin staining and transmission electron microscopy. The expressions of extracellular matrix proteins [fibronectin (FN) and collagen type IV (Col-Ⅳ)] in the glomerular mesangium was assessed by immunofluorescence. Levels of inflammatory cytokines [interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)] and proteins related to high mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/nuclear factor-κB (NF-κB) signaling pathway were detected by ELISA assay and Western blotting. In vitro experiments were performed to investigate the effect of icariin on extracellular matrix protein expressions in high glucose-induced SV40 MES-13 cells. Results In vivo experiments results showed that high-dose icariin significantly reduced the body weight, urinary protein, blood lipid and serum creatinine levels in DKD mice (P < 0.01, 0.001), alleviated pathological changes such as mesangial expansion, basement membrane thickening and podocyte fusion (P < 0.001), reduced the levels of IL-1β, IL-6 and TNF-α in plasma and renal tissue (P < 0.01, 0.001), decreased the infiltration of macrophages in the kidney, and significantly inhibited the protein expressions of HMGB1, TLR2, TLR4 and p-p65 in renal tissue (P < 0.001). In vitro experiments results showed that icariin inhibited the expressions of FN and Col-Ⅳ in high glucose-induced glomerular mesangial cells. Conclusion Icariin could effectively inhibit HMGB1/TLRs/NF-κB signaling pathway, thereby attenuating renal inflammatory response and abnormal extracellular matrix accumulation, ultimately improving pathological injury in DKD.

Objective By conducting a whole-genome identification and functional analysis of auxin response factors (ARFs) family members in Gentiana rigescens, this study investigate their potential roles in the thermosensitive corolla opening-closing movement of its corolla. Methods Based on whole-genome data and transcriptome data, bioinformatics methods were used to analyze the physicochemical properties, conserved motifs, gene structure, cis-acting elements, and evolutionary relationships of the G. rigescens ARFs (GrARFs) gene family. Real-time quantitative reverse transcription PCR (RT-qPCR) technology was employed to detect the expression patterns of GrARFs genes under different opening and closing states. Additionally, subcellular localization experiments were conducted to verify the protein localization of GrARF9, so as to preliminarily analyze the biological functions of the GrARFs gene family. Results A total of 21 GrARFs were identified in the G. rigescens genome, encoding 612—1 065 amino acids. Their relative molecular weights ranged from 68 082.29 to 118 117.97, and their isoelectric points spanned 5.52—8.43. The secondary structure was dominated by random coils. Phylogenetic tree analysis classified the ARFs in G. rigescens into four subgroups, namely Group A, Group B, Group C, and Group D. Most GrARFs contained Auxin-resp and B3 DNA-binding domains. The promoter cis-acting elements of GrARFs were rich in hormone-responsive and light-responsive elements. The 21 GrARFs were unevenly distributed across eight chromosomes. Collinearity analysis revealed that the GrARFs in G. rigescens were relatively conserved among dicotyledonous plants and shared a considerable number of collinear pairs with the functionally characterized ARFs from Rosa hybrida. All 21 GrARFs genes exhibited differential expression during the thermosensitive process of G. rigescens corollas. Results of subcellular localization experiments showed that the GrARF9 protein was localized in the nucleus, displaying the nuclear localization characteristic of transcription factors. Conclusion The results of this study preliminarily clarify the expression pattern of GrARFs in the thermosensitive movement of G. rigescens, and lay a foundation for further research on the function of GrARFs in the corolla movement of G. rigescens.

Objective To develop an icariside II nanoemulsion (NE-ICS II) to enhance oral bioavailability and improve efficacy against cerebral ischemia-reperfusion injury (CIRI). Methods NE-ICS II was prepared by ultrasonic emulsification and its physicochemical properties were characterized. Pharmacokinetic parameters and brain distribution were systematically evaluated. Therapeutic efficacy was assessed in rats subjected to middle cerebral artery occlusion (MCAO) by measuring infarct volume, neurological deficit scores, and oxidative stress and inflammatory markers. RNA sequencing was performed to elucidate the underlying mechanisms. Results NE-ICS II showed a mean particle size of (147.59 ± 0.71) nm and an encapsulation efficiency of (84.85 ± 5.47) %. NE-ICS II increased the oral bioavailability of ICS II by 2.4-fold and significantly enhanced its accumulation in the brain. Therapeutic oral administration of NE-ICS II markedly improved neurological function, reduced infarct volume, and attenuated oxidative stress and inflammatory responses in MCAO rats. RNA sequencing revealed that NE-ICS II may downregulate signaling pathways associated with oxidative stress and inflammation. Conclusion NE-ICS II substantially improves the oral bioavailability of ICS II and enables effective treatment of CIRI at a low dose, providing a promising strategy for efficient brain delivery of ICS II and for the treatment of central nervous system diseases.