Chloranthus is a genus within the family Chloranthaceae, comprising perennial herbs or shrub plants. There are 15 recognised species of Chloranthus. The chemical constituents of Chloranthus plants are diverse and feature many novel sesquiterpene skeletons. Their pharmacological activities are extensive, warranting in-depth research and discussion. This paper reviews and discusses the newly discovered chemical and biological activities of Chloranthus from the past 10 years, including 241 terpenoids, 26 phenylpropanoids, 17 flavonoids, 13 amides, 8 phenolic acids and 14 other compounds identified from 2013 to 2023. In terms of biological activity, extensive studies on the anti-tumour, anti-inflammatory, antibacterial, and other effects of Chloranthus plants are summarised. In this paper, the phytochemistry and pharmacology of Chloranthus were reviewed, and the active structure-activity relationship of these compounds was discussed in order to comprehensively summarise the related research progress of Chloranthus.

BackgroundCordyceps sinensis is a well-known traditional Chinese medicine with antitumor activity. Isaria felina (IF) is a novel fungus isolated from the fruiting bodies of Cordyceps sinensis. IFA was prepared by fermentation and ethanol extraction. This study investigated the antitumor effects of the ethanol extract of IF (IFA) on hepatocellular carcinoma (HCC) using H22 hepatocellular carcinoma cells and a mouse xenograft model.MethodsIn vitro, CCK-8 assay was used to assess cell viability. Annexin V-PE/7AAD flow cytometry, RT-PCR, and Western blot were performed to detect apoptosis and related pathways. In vivo, H22 tumor-bearing mice were treated with IFA by gavage. TUNEL staining, immunohistochemistry, blood routine, serum biochemistry, and ELISA were applied to evaluate tumor apoptosis, liver function parameters, and immune parameters.ResultsIFA dose-dependently inhibited H22 cell proliferation. Flow cytometry showed that IFA induced late-stage apoptosis. RT-PCR and Western blot revealed upregulation of P53, Bax, Cyt C, and Caspase-3, and downregulation of Bcl-2, indicating activation of the P53/Bax/Bcl-2/Cyt C/Caspase-3 pathway. In vivo, IFA suppressed tumor growth, increased TUNEL-positive apoptotic cells, and enhanced serum TNF-α while reducing TGF-β, without impairing liver or kidney function.ConclusionsIFA inhibits HCC growth by inducing mitochondrial apoptosis via the P53 pathway and by modulating host immunity, highlighting its potential as a natural therapeutic agent for HCC.

The overexpression of SHP2 in various cancers establishes it as an attractive therapeutic target. Growing evidence indicates that the scaffold function of SHP2 contributes significantly to its oncogenic signaling and tumorigenesis. Unlike traditional inhibitors, PROTACs can simultaneously eliminate both the enzymatic and scaffold functions of the target protein, representing a more promising therapeutic strategy. Herein, we report the design and synthesis of SHP2 PROTACs that recruit the DCAF16 E3 ligase for targeted SHP2 degradation. Among which, SK8 exhibited the most potent anti-tumor activity. SK8 induced SHP2 degradation in a concentration- and time-dependent manner via the ubiquitin-proteasome system. Notably, under the tested experimental conditions, SK8 produced greater inhibition of cell proliferation, migration, and invasion, together with increased apoptosis, compared with SHP099. Preliminary mechanistic studies revealed that this enhanced potency stemmed from a more profound inhibition of RAS/MAPK and PI3K/AKT/mTOR signaling, coupled with the reversal of IFN-γ/JAK/STAT1 suppression. Overall, our findings support the potential of SHP2-targeted protein degradation as an alternative strategy to enzymatic inhibition and provide a promising starting point for the further development of SHP2 degraders.

Seven previously undescribed diterpenoids, including three myrsinane diterpenoids (1-3), one premyrsinane diterpenoid (4), two tigliane (5-6) and one bicyclic diterpenoid (7), as well as eight known myrsinane-type diterpenoids (8-15) have been isolated from the dried roots of Euphorbia prolifera Buch.-Ham. ex D. Don. The structures of the previously undescribed diterpenoids were determined by HR-ESI-MS, 1D and 2D NMR, ECD and other methods. Meanwhile, all compounds were evaluated for their anti-inflammatory activity in vitro, and the results showed that compounds 5, 8 and 10 showed significant inhibitory effect on NO production induced by LPS in RAW 264.7 macrophages, compared to the positive control drug dexamethasone.

Through phytochemical research on Euphorbia peplus, fourteen ingenane-type diterpenoids were identified. Among them, four previously undescribed compounds (1-4) were characterized, along with ten known analogues (5-14). Structural determination of the previously undescribed compounds was achieved by integrating data from HRESIMS, 1D, and 2D NMR spectroscopic analysis. A subset of the isolates, specifically compounds 1, 3, 4, 6, 11, 12, and 14, demonstrated significant reduction of NO production in LPS-stimulated RAW 264.7 macrophages, indicating anti-inflammatory potential. This investigation enhances the structural diversity among known ingenane diterpenoids and highlights their bioactivity relevant to inflammatory response modulation. Target screening and molecular docking suggest that the anti-inflammatory effect of compound 3 is likely mediated through its binding to human liver glycogen phosphorylase and protein kinase MK2.

Drug-perturbation proteomics provides a direct molecular readout of compound-induced cellular states, but its high dimensionality and limited interpretability hinder its use for mechanism-oriented drug discovery. Here, we present DeepHeal, an interpretable consensus representation framework that transforms drug-induced proteomic responses into biologically readable and experimentally actionable antineoplastic response programs. Using an HCT116 perturbation atlas comprising 875 compounds and 9,960 protein features, DeepHeal integrates ensemble variational autoencoders, supervised contrastive learning, consensus latent-variable aggregation, and protein-level attribution. A label-independent Average branch captures recurrent proteomic variation, whereas a complementary label-aware SupCon branch concentrates known antineoplastic structure. The resulting latent programs are mapped back to proteins, pathways, and interaction networks, revealing shared cell-cycle, DNA-replication, stress-response, metabolic, proteostasis, apoptosis-related programs, together with mechanism-dependent response heterogeneity. DeepHeal prioritized 19 initially unlabeled compounds for experimental follow-up, of which seven inhibited HCT116 cells with IC₅₀ values below 10 μM, including two compounds with nanomolar activity. Without retraining, DeepHeal representations further recovered antineoplastic response states across 566 external proteomic perturbation profiles spanning multiple cellular contexts. Together, these findings establish DeepHeal as, to our knowledge, the first proteomics-first interpretable consensus representation framework that transforms large-scale drug-perturbation proteomes into protein- and pathway-resolved response programs for cross-context anticancer candidate prioritization and experimental validation.

Astragalus membranaceus polysaccharides (APS), bioactive macromolecules derived from the roots of Astragalus membranaceus (Fisch.) Bge., exert immunomodulatory, anti-inflammatory, antioxidant, and metabolic regulatory effects. However, the molecular features and compositional profiles of APS are strongly influenced by extraction procedures, purification strategies, and subsequent chemical or physical modifications. This review comprehensively evaluates APS extraction, structural characterization, biological activities, and application, with particular emphasis on the evidence linking preparation-dependent structural variation to biological responses. Emerging extraction strategies may enhance recycling efficiency; however, there is insufficient reporting on their relevance to polysaccharide integrity, residual solvent safety, and large-scale reproducibility. Structurally, APS comprises diverse polysaccharide architectures, including α-(1 → 4)-D-glucan-like regions, pectic domains such as rhamnogalacturonan I and homogalacturonan, and arabinogalactan-related side chains. Available evidence suggests that molecular weight, monosaccharide composition, branching architecture, and chemical modification may influence biological responses. However, because many APS preparations remain incompletely characterized and structural and bioactivity analyses are often conducted across different studies or non-comparable fractions, causal structure-activity relationships remain difficult to establish. Reported biological activities are mainly supported by cellular and animal studies and involve immune regulation, redox modulation, metabolic regulation, and gut microbiota-associated mechanisms. Future studies should integrate reproducible APS preparation with standardized structural characterization, mechanistic validation, and clinical evaluation to better define the links between preparation, structural variation, and biological activity.

Molecular-network-guided mining of a diterpenoid extract from Euphorbia prolifera Buch.-Ham. ex D.Don roots highlighted a cluster assigned to myrsinane-type diterpenoids. This directed the isolation of six undescribed myrsinanes, one tigliane-type diterpene and 27 known diterpenoids. Structures were established by 1D/2D NMR, HR-ESI-MS, ECD calculations, and X-ray crystallography. Notably, (2S,3S,4R,5R,6R,7R,9S,11S,12R,13S,14S,15R)-3β-O-propionyl-5α-O-benzoyl-7β-O-acetyl-17,14-oxo-premyrsinol (1) is the first myrsinane-type diterpene with 14/17-oxygen bridge. All compounds exhibited their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages. Compounds 18, 19, and 31 showed significant inhibitory effects, and the IC50 values of compound 19 reached 8.7 ± 1.31 μM.

Infections caused by pathogenic bacteria, particularly Staphylococcus aureus and Escherichia coli, present severe challenges to public health due to their virulence and persistence. The search for novel antimicrobial scaffolds from natural sources is a critical strategy to combat these threats. Rhododendron dauricum, an economic plant resource with a unique chemical profile, has recently garnered attention for its potential antimicrobial properties; however, the effective utilization of its bioactive metabolites is often hindered by poor solubility. In this study, nine meroterpenoids, daurichromenes M-R (1-6), rhodonoids NP (8-10), along with four known analogues (7 and 11-13) and two known triterpenoids (14-15) were isolated from the twigs and leaves of R. dauricum. The structures of undescribed compounds were identified through the analysis of spectroscopic data (MS, UV, NMR), comparison of the experimental and calculated ECD data, modified Mosher's method, and Snatzke's method. Addressing the limitations of natural product application, we discovered that the major constituent, grifolin (7), spontaneously self-assembles into carrier-free nanoparticles. Unlike its monomeric form, which exhibits weak biological activity, grifolin nanoparticles (GNPs) exhibited dose-dependent antimicrobial activity against Staphylococcus aureus, with a minimum inhibitory concentration (MIC) of 125 μg/mL. Molecular dynamics (MD) simulations and UV-vis analysis demonstrated that GNPs self-assemble via molecular aggregation driven by π-π stacking, hydrogen bonding, and electrostatic interactions, leading to the formation of nanofiber clusters. Crucially, this carrier-free nanotechnology improves the stability of bioactive compounds without introducing non-degradable synthetic carriers. This study not only enriches the chemical diversity of R. dauricum but also provides a structure-based, green chemistry strategy for designing self-assembling bacteriostatic agents to unlock the therapeutic potential of natural products against bacterial pathogens.

Curcumae Rhizoma is obtained from the dried rhizomes of Curcuma phaeocaulis Valeton, Curcuma kwangsiensis S. G. Lee et C. F. Ling and Curcuma wenyujin Y. H. Chen et C. Ling. It is usually used to treat dysmenorrhea, amenorrhea, irregular menstruation, pelvic blood stasis, abdominal epigastric tumor, arrhythmia, coronary heart disease, stroke, indigestion, gastritis, etc. Sesquiterpenoid and diarylheptanoid compounds are the main components in Curcumae Rhizoma. In this paper, the chemical structure and skeleton characteristics of 319 compounds were systematically summarized since 2001, including 263 terpenoids (1–263) and 55 diarylheptanoids (264–318). Among these, sesquiterpenoids are the most (24–252), mainly including guaiacane-type, eudesane-type, germarane-type, calabane-ype, etc. In addition, we also summarized the pharmacological activities of compounds isolated from Curcumae Rhizoma. The biosynthesis of chemical components from Curcumae Rhizoma was summarized for the first time. This review also provides significant reference for the structural analysis, biogenic pathways, and pharmacological activities of the compounds in Curcumae Rhizoma.

Targeted protein degradation, particularly through molecular glue degraders (MGDs), offers a promising strategy for targeting "undruggable" proteins. However, existing fluorescence-based screening approaches, such as time-resolved fluorescence resonance energy transfer, may be constrained by conformational changes or inefficient labeling of targets, necessitating more efficient screening approaches. Here, we present a MGDs screening approach based on surface plasmon resonance (SPR) coupled with degradomics and interactomics (SPR-DI). This approach leverages the high-throughput and label-free SPR for screening E3 ligands, followed by an unbiased "dual filter" of degradomics and interactomics to identify candidate proteins of interests (POIs). The feasibility of SPR-DI was validated using previously established MGD VH032, which can drive VHL to induce CDO1 degradation. Employing VHL and Keap1 as drivers E3, we then screened a natural product library and successfully identified triptolide and pycropodophyllin as potential MGDs. Subsequent investigations demonstrated that triptolide facilitates VHL-mediated degradation of IMP3, whereas picropodophyllin promotes Keap1-mediated degradation of DDX52 and LDHB. These degradation events were confirmed to depend on the respective E3 and ubiquitin-proteasome system, underscoring the capacity of these compounds to induce ternary complex formation. In conclusion, the establishment of SPR-DI provides a promising tool for the discovery of MGDs and their corresponding POIs, offering instructive insights to advance future MGD screening methodologies.

Drug-perturbation proteomic profiles encode mechanism-relevant phenotypes, but robust latentspace models for large-scale perturbation proteomics remain underdeveloped. Here we developed DeepHeal, a framework comprising complementary consensus variational autoencoder atlases derived from 875 compound-induced proteomic log2FC profiles in HCT116, and used it for phenotype-based drug discovery, mechanism-of-action analysis and candidate prioritization. To our knowledge, this is the first application of variational autoencoders to large-scale drug-perturbation proteomics. Our primary atlas combined supervised contrastive learning with a 600-model consensus VAE ensemble so that the full cohort contributed to representation learning while 448 labelled compounds imposed class-aware structure; a matched unsupervised average-profile atlas served as reference. The supervised atlas retained 257 consensus latents and achieved perfect within-cohort separation of antineoplastic and nonantineoplastic compounds with both LGMLVQ and the best-performing AutoGluon classifier identified for the supervised branch (KNeighbors), whereas the average-profile atlas retained 194 latents and was weaker for classification (the best-performing AutoGluon classifier identified for the average-profile branch (TabM) accuracy 0.767, AUROC 0.756; LGMLVQ accuracy 0.767, AUROC 0.738). Pathway interpretation revealed a trade-off between density and breadth: the supervised atlas concentrated signal in cell-cycle, replicationstress and DNA-damage programmes and recovered 100 canonical pathways overall, whereas the averageprofile atlas preserved broader normalized pathway diversity per 100 latents in both canonical and oncogenic collections. Applying a stringent four-model consensus rule to 427 previously unlabelled compounds identified 19 high-confidence candidates, including 14 rediscovered external antineoplastics and a smaller set of mechanistically plausible repurposing candidates led by JP1302, BAY 61-3606 and SB 225002. Cluster-level and macro-mechanism analyses further resolved cohort-wide and subgroup-specific pathway structure across the atlas. These results establish DeepHeal as a practical framework for perturbation proteomics and show that proteomic latent atlases can support phenotypic screening, mechanism-of-action analysis and hypothesis generation within large drug-response resources.

Oxaliplatin (L-OHP) is a first-line chemotherapeutic agent for both advanced colorectal cancer (CRC) and postoperative adjuvant therapy. However, the development of acquired L-OHP resistance remains a major clinical obstacle. Here, we identify Tubocapsenolide A (TA), a natural withanolide isolated from Tubocapsicum anomalum , as a potent antitumor agent that not only suppresses CRC growth but also effectively reverses acquired L-OHP resistance. Using a PROTAC-based target deconvolution strategy combined with biophysical validation, we demonstrate that PLK1 is the direct functional target of TA. PLK1 is aberrantly overexpressed in L-OHP-resistant CRC and negatively correlates with patient sensitivity to L-OHP. Mechanistically, overexpressed PLK1 hyperphosphorylates the adaptor protein CEP55 to recruit the ESCRT machinery, driving a previously unappreciated PLK1-CEP55-ESCRT-dependent vesicular extrusion process. This enables resistant cells to rapidly clear L-OHP-induced damage through γ-H2A.X⁺ nuclear budding and TOM20⁻/PDH⁺ mitochondrial-derived vesicles, thereby preserving organelle integrity and promoting cell survival. By directly binding and inhibiting PLK1, TA disrupts the CEP55-ESCRT-dependent membrane scission machinery, leading to intracellular accumulation of damaged components. Consequently, it triggers severe nucleolar stress and mitochondrial dysfunction, ultimately inducing death in L‑OHP‑resistant cells. Collectively, our findings uncover a novel PLK1-CEP55-ESCRT-driven vesicular extrusion mechanism underlying L-OHP resistance and establish targeting this axis as a promising therapeutic strategy for chemorefractory CRC. TA represents a valuable lead compound for the development of new treatments against L-OHP-resistant CRC.

OBJECTIVE:The therapeutic equivalence between formula granules and traditional co-decoction remains a major clinical controversy. This study aims to investigate the scientific basis for the equivalence between formula granules and herbal piece decoctions using Jiao-Tai-Wan in the diabetic mouse model. METHODS:This study employs Jiao-Tai-Wan using db/db diabetic mice as a disease model to investigate the scientific basis of equivalence between formula granules and herbal piece decoctions through multidimensional approaches. Using UPLC-QE- Orbitrap-MS, novel compounds generated during co-decoction were identified. Then, the hypoglycemic effects of formula granules, mixed individual decoctions, and combined decoction were systematically compared in db/db mice, complemented by 16S rRNA sequencing of gut microbiota and molecular docking of bioactive compounds with taste receptors. RESULTS:Twenty-nine new co-decoction-related compounds were detected. All Jiao-Tai-Wan groups exhibited a more pronounced reduction in fasting blood glucose compared to the metformin group(p < 0.05), with efficacy descending as follows: co-decoction > mixed decoction > formula granules. Each preparation distinctly modulated gut microbiota. Strong binding (≤ -5.0 kcal/mol) was confirmed between main constituents (e.g., berberine, cinnamic acid) and receptors (TAS2R46, TRPV1). CONCLUSIONS:This study identified novel compounds generated during the co- decoction of Jiao-Tai-Wan through UPLC-QE-Orbitrap-MS. Using a multi- dimensional approach encompassing efficacy comparison, gut microbiota modulation, and molecular docking, it preliminarily elucidated that these co-decoction reaction products may constitute the material basis and potential mechanism underlying the efficacy differences between formula granules and traditional combined decoctions. These findings offer important mechanistic insights into co-decoction reaction and validate potential clinical applications of granule formulations.

Selenium (Se) biofortification of microalgae offers a sustainable strategy to produce Se-enriched biomass for functional food and feed applications. However, the metabolic trade-offs between Se tolerance, biomass productivity, and bioactive compound accumulation remain poorly understood. This study investigated the physiological, transcriptomic, and metabolomic responses of C. pyrenoidosa RLXCh3 to sodium selenite treatment (0–300 mg/L) to identify the optimal biofortification conditions during high-density fermentation. Physiological screening revealed that 100 mg/L selenite for 24 h induced moderate, sub-lethal stress characterized by 15.09% reduction in OD₆₈₀ and 11.07% reduction in dry biomass, while preserving cellular integrity. Pilot-scale (500 L) fermentation achieved total Se accumulation of 1670 mg/kg dry weight with 99.8% organic Se conversion efficiency and 85.54% Se removal from the culture medium. Integrated transcriptomic and metabolomic analyses revealed that C. pyrenoidosa simultaneously downregulates energy-intensive pathways including starch/sucrose metabolism and the TCA cycle, while upregulating aromatic compound biosynthesis and antioxidant related pathways. This metabolic trade-off might have redirected carbon flux from growth toward antioxidant defense, resulting in 81.4% and 81.1% increases in total flavonoids and polyphenols, respectively, and 23.6–36.0% enhancement in total antioxidant capacity. This study establishes 100 mg/L sodium selenite for 24 h as an effective, scalable biofortification regime for producing high-value Se-enriched biomass for industrial application.

Influenza A virus continues to pose a significant global health threat, causing seasonal epidemics and occasional pandemics. Viral transcription and replication rely on the heterotrimeric polymerase complex where the PB2 subunit initiates RNA synthesis through binding to the host mRNA cap structure. In this study, we began with a structure-activity relationship analysis of the pioneering PB2 inhibitor VX-787. Through computer-aided drug design, combined with considerations of molecular docking scores, ADMET property predictions, and a prodrug esterification strategy, we ultimately designed eight novel compounds. Cytopathic effect assays demonstrated that all compounds exhibited superior inhibitory activity against both H1N1 and H3N2 strains compared to oseltamivir acid. In particular, compounds 11 and 15 displayed nanomolar-level activity against H1N1, while compound 18 showed activity against H3N2 superior to that of VX-787. These findings propose a rational design strategy that may offer new avenues for addressing the resistance and metabolic limitations associated with VX-787 and hold potential for advancing the development of next-generation PB2-targeted anti-influenza therapeutics.

Anticancer drugs are usually classified by structure, ATC codes, or annotated targets, which often poorly reflect the cellular states they induce. We generated a proteomic perturbation atlas of 367 anticancer compounds in HepG2 cells using TMTpro-based quantitative mass spectrometry. Chemical fingerprints showed no natural structural clustering, motivating a biology-driven approach. Unsupervised graph-based clustering of drug-induced proteomic changes identified ten Drug Response Phenotypes (DRPs) that are statistically stable, pathway-resolved, and largely orthogonal to ATC and target-class annotations, establishing proteomic phenotypes as an independent classification axis. Across compounds, we observed a conserved "growth arrest-defense activation" state that correlated with cytotoxicity. Elastic-net and random forest modeling yielded a nine-protein Core Proteomic Signature of Pan-Drug Cytotoxicity (CPS-9) that summarizes major death/stress and survival/proliferation modules, while explicitly excluding mechanisms driven predominantly by post-translational regulation. A proteomic similarity network recovered known mechanism-of-action cohorts and nominated cross-category repurposing candidates. Finally, projection of 12 plant-derived small molecules, including three active/inactive analog pairs, into the DRP/CPS-9 space provided proofof-concept for target-agnostic mechanistic annotation of natural products. Together, this work delivers a scalable proteomic reference framework for de novo classification, repurposing hypothesis generation, and mechanism-oriented evaluation of anticancer agents.

Zanthoxylum bungeanum Maxim. is widely used worldwide as a food and health supplement, recognized for its diverse nutritional and medicinal benefits. Z. bungeanum contains various active components, including amides, alkaloids, flavonoids, phenylpropanoids, terpenes, and free fatty acids. Multiple extracts and isolated compounds from Z. bungeanum have demonstrated various biological activities, including antitumor, anti-inflammatory, neuroprotective, antioxidant, and antimicrobial activity. Additionally, Z. bungeanum shows promise for future research and development in food preservation and cosmetic applications. This review examines the chemical constituents, biological activities, and applications of Z. bungeanum, exploring the multifaceted value of this important plant resource in depth with the aim of providing useful references for its development and utilization.

Background: Diabetic foot, a severe complication of diabetes, is characterized by chronic refractory wounds. Sanhuang Oil, a topical herbal formula, demonstrates significant therapeutic effects including antibacterial, anti-inflammatory, and immunomodulatory activities. However, its active constituents and mechanisms of action against diabetic foot remain to be elucidated. Methods: In this study, the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS. Subsequently, the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking. Additionally, diabetic mouse model was established in ICR mice using a combination of a high-fat diet (HFD) and streptozotocin (STZ) chemical induction. A full-thickness skin defect was created on the dorsum of the mice. Wound healing and the healing rate were observed following Sanhuang Oil intervention. The mechanism underlying Sanhuang Oil's promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination (H&E staining). Results: A total of 97 active ingredients were identified from Sanhuang Oil. Network pharmacology analysis predicted 543 common targets, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 203 relevant pathways. Molecular docking further confirmed high binding affinity (binding energy <= -5.0 kcal/mol) between specific active components in Sanhuang Oil (e.g., coptisine, phellodendrine, baicalein) and key targets associated with diabetic foot ulcers (e.g., EGFR, AKT1, STAT3). In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group (P < 0.001). HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound, reduced inflammatory cell infiltration, and increased collagen deposition and fibroblast proliferation. transcriptomic analysis identified Pdk4, Ttn, Csrp3, Actn2, Myoz2, Tnnc2, Myod1, Myog, Myot, and Myf6 as key regulatory proteins involved in promoting wound healing. Conclusion: Sanhuang Oil promotes wound healing in diabetic ulcer mice, potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function. These findings provide novel insights into the multi-target, multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.