Ethnopharmacological relevance: Jingfang Baidu San (JF) is a classic traditional Chinese medicine（TCM）formula that has been widely used in clinical practice for hundreds of years. While its efficacy in treating Feng Han (wind-cold, FH) common cold has garnered increasing attention, its underlying mechanism of action remain incompletely understood.Aim: This study aimed to evaluate the therapeutic effect of JF on wind-cold common cold and to elucidate its molecular mechanism.Methods: A common FH model in mice was established by exposing them to continuous wind and cold stimulation for 7 days. The therapeutic efficacy of intragastric administration of JF was first evaluated by detecting behavioral changes, body weight, anal temperature, and energy metabolism, followed by histopathological examination of lung tissues via hematoxylin-eosin (HE) staining. To investigate the underlying mechanisms, we performed lungtranscriptomic analysis sequencing to identify key regulatory network. Subsequently, the expression of inflammatory cytokines in serum and lung tissues was detected by using enzyme-linked immunosorbent assay (ELISA), and the expression of key proteins was analyzed by immunofluorescence, immunohistochemistry and Western blotting.Results: JF significantly alleviated symptoms, as evidenced by increased body weight, improved energy metabolism, and amelioration of behavioral impairments such as listlessness and cough. Histologically, JF markedly attenuated lung pathological damage and reduced the levels of inflammatory factors (including IL-6, IL-1β, and TNF-α) in serum and lung tissues. Mechanistically, T transcriptome sequencing and in vivo analyses revealedthat JF restored M1/M2 macrophage immune homeostasis by upregulating the expression of Dectin-1 (Clec7a). This upregulation led to the inhibitionof the NF-κB/TGF-β signaling pathway, which subsequently reduced the expression of macrophage-derived matrix-remodeling factors (MMP12/19), downregulated the expression of collagen Col1a1 and Col3a1, pro-fibrotic factor SPP1, and decreased the neutrophil marker Elane, collectively improving pulmonary tissue matrix remodeling and inflammatory infiltration.Conclusion: Our findings demonstrate that JF alleviates lung injury in FH common cold by upregulating the expression of Dectin-1 in macrophages to restore M1/M2 macrophage immune homeostasis, thereby inhibiting the NF-κB/TGF-β signaling pathway and improving lung tissue matrix remodeling and inflammatory infiltration. This study provides novel mechanistic insights into the therapeutic action of JF in the treatment of the common FH cold and supports its clinical application.

Cardiovascular disease (CVD) remains the foremost cause of global mortality. Hypertension and dyslipidemia, frequently coexisting, exert synergistic effects that substantially elevate CVD risk via interconnected molecular pathways. This review systematically examines the synergistic mechanisms underlying their combined contribution to CVD progression, with a focus on key pathways such as the RAAS/PPAR axis, AMPK/SIRT1 signaling, and NLRP3 inflammasome activation. We highlight how their interplay disrupts endothelial function, aggravates oxidative stress, and promotes chronic inflammation, thereby causing vascular damage and atherosclerosis. Furthermore, we examine emerging targeted therapies, including the combination of RAAS inhibitors with statins, PCSK9 inhibitors, as well as newer agents such as SGLT2 inhibitors and GLP-1 receptor agonists. These approaches represent promising multi-target strategies for improving clinical outcomes. Ultimately, this review underscores the need for a precision medicine framework that addresses the synergistic pathophysiology of hypertension and dyslipidemia, paving the way for personalized, pathway-integrated interventions aimed at restoring metabolic-vascular homeostasis rather than merely treating disease.

Gout develops as a consequence of longstanding hyperuricaemia leading to the deposition of monosodium urate crystals that can trigger episodes of acute inflammation, and in severe cases, impairment of vital organ function. In clinical practice, the treatment of gout has long relied on Western medicines. However, they exhibit a single mechanism of action for gout treatment and may increase the burden on target organs (e.g. allopurinol-induced liver injury and benzbromarone-associated elevated risk of kidney stones), which easily leads to the formation of a vicious cycle of 'hyperuricaemia -gouty arthritis - tissue damage'. This article summarized 129 natural products (NPs) (i.e. monomers) for gout treatment published up to August 2025, focusing on their potential mechanisms underlying the regulation of uric acid metabolism and inhibition of gouty arthritis, as well as their protective effects on target organs (i.e. improving renal function and restoring the balance of gut microbiota). Besides, the potential and prospects of NPs based on nanomaterials for gout treatment have been pointed out. In conclusion, this article comprehensively reviewed the treatment of gout by NPs through the synergistic effect of 'pathogenic mechanism regulation - target organ protection'. This review will provide a reference for improving the prognosis of gout patients and breaking through the limitations of existing therapeutic approaches.

Characterized by a total or partial shortage of insulin, diabetes is a chronic metabolic condition. Its widespread occurrence and related complications present a significant global public health issue. Ganoderma lucidum (Curtis) P. Karst. 1881 (Polyporaceae), a valuable traditional Chinese medicine, contains polysaccharides as its primary active metabolites. Polysaccharides exhibit virous pharmacological properties including hypoglycemic, hypolipidemic, immunomodulatory, and anti-tumor effects. Although recent research has increasingly investigated the potential of G. lucidum polysaccharides (GLPs) to manage diabetes and its complications, a systematic integration of these findings is lacking. The review comprehensively summarizes relevant literature retrieved from databases including PubMed, Sci-Hub, Science Direct, Scopus, and Open Access Library. GLPs demonstrates defensive impacts against diabetes and its associated complications including nephropathy, hepatopathy, cardiomyopathy, refractory wound healing, neuropathy, retinopathy, and erectile dysfunction--through mechanisms involving oxidative stress modulation, glucolipid metabolism regulation, anti-apoptosis, islet cells repair, and the gut microbiota remodeling. Furthermore, drug combination strategies and novel formulation development represent promising directions for future applications This review provides a theoretical foundation for the advancement of effective and low toxicity natural therapies for diabetes based on GLPs.

Abstract Objective: To address the critical gap in traditional gout animal models that fail to recapitulate the traditional Chinese medicine (TCM) syndrome of Damp-Heat Pouring Downward Syndrome (DHPDS), this study aims to establish a disease-syndrome integrated model that aligns with TCM theory. Materials and Methods: Six DHPDS gout rat models were developed by integrating endogenous dampness-heat induction (high-fat diet, ethanol, and ginger extract) and exogenous pathogenic stimulation (artificial climate chamber), followed by phenotypic, biochemical, and histopathological evaluations. Serum metabolomic profiling was performed using ultra-high-performance liquid chromatography-Q/Orbitrap/LTQ MS. Non-negative matrix factorization (NMF) distilled clinical topic features from data of 92 patients with DHPDS gout. Model fitting analysis employed a dual-module framework: NMF-derived feature coefficients were converted to weighted phenotypic scores, and metabolomic congruence analysis was used to evaluate biomarker overlap between animal models and clinical cohorts. Results: Comprehensive evaluations (phenotypic, biochemical, and histopathological) confirmed the successful establishment of DHPDS gout rat models. Metabolomic profiling detected 31, 37, 38, 38, 46, and 42 differentially expressed metabolites in models 1–6, primarily linked to gout-related pathways: purine/pyrimidine metabolism, amino acid homeostasis, lipid metabolism, and arachidonic acid metabolism. Clinical topic features of DHPDS gout included high uric acid, high low-density lipoprotein, high triglyceride, diet reduction, and high creatinine. Model 5 demonstrated superior congruence with clinical DHPDS gout features, achieving the highest composite fitting score (172/200). Conclusions: This study established six DHPDS gout animal models guided by TCM theory. Through multimodal fitting analysis combining clinical features with metabolomic profiling, Model 5 was identified as the most clinically representative. The multimodal fitting framework establishes a novel paradigm for precision modeling of TCM syndromes.

Hyperuricemia (HUA) is a major risk factor for gout and multiple metabolic disorders. Although serum uric acid (UA) is the gold standard for HUA diagnosis, it fails to reflect early metabolic disturbances and shows limited predictive value for asymptomatic HUA. This study sought to elucidate the pathological mechanisms underlying HUA and identify novel diagnostic biomarkers beyond UA. This study enrolled 195 patients with HUA and 98 healthy controls. Global metabolomics and proteomics profiling were performed to characterize molecular alterations underlying HUA. Based on the biological relevance of the shared dysregulated pathways, a pathway correlation network was constructed to elucidate the pathological mechanisms driving HUA initiation and progression. Furthermore, diagnostic biomarkers for HUA were identified using machine learning algorithms, and were validated with an external cohort. HUA patients exhibited distinct metabolic and proteomic profiles compared with healthy controls. Integrated multi-omics pathway analysis revealed that peroxisome proliferators-activated receptor signaling pathway, arachidonic acid metabolism, purine metabolism, pyrimidine metabolism and sphingolipid signaling pathway were significantly dysregulated in HUA. Among them, arachidonic acid metabolism was identified as a hub pathway involved in HUA progression. Furthermore, a metabolite panel consisting of cysteine-S-sulfate, glycerophosphocholine and 4-hydroxyphenylpyruvic acid was screened by machine learning and validated in an independent cohort, which showed slightly higher diagnostic performance for HUA than UA. This study reveals the core metabolic and protein regulatory networks of HUA, and identifies a novel serum metabolite panel for the diagnosis of HUA. These findings provide new insights for improved clinical diagnosis and management.

Cancer remains a formidable global health challenge, characterized by alarmingly high incidence and mortality rates. Traditional clinical therapies are often accompanied by obvious toxicity and side effects, highlighting the urgent need to develop safer and more effective therapeutic alternatives. In recent years, polysaccharides have emerged as promising candidates for anti-tumor drugs due to their wide sources, high biocompatibility and low toxicity. This review summarizes recent advances in anti-tumor effects of polysaccharides, covering their underlying mechanisms, key signaling pathways and selective toxicity characteristics. Polysaccharides exert synergistic anti-cancer effects through multi-target, multi-pathway mechanisms, including the induction of immune cell polarization and tumor cell apoptosis, inhibition of tumor cell migration and angiogenesis, and modulation of key signaling pathways such as P53, NF-κB, and Wnt/β-catenin. Among these, polysaccharides with specific monosaccharide compositions, optimal molecular weights, β-glycosidic linkages, triple-helix conformations, or those that are chemically modified, exhibit enhanced biological and anti-tumor activities. Future efforts should focus on elucidating structure-activity relationships, developing targeted delivery systems to improve bioavailability and tumor specificity, and advancing large-scale, multi-center, long-term clinical trials to support the development of safe and effective polysaccharide-based anti-cancer therapeutics.

Ethnopharmacological relevance Danggui Buxue Decoction (DBD) is a classic traditional Chinese medicine formula that has shown significant efficacy in treating blood deficiency syndrome (BDS), though its mechanisms of action remain unclear. Aim of the study To identify the absorbed bioactive components of DBD and elucidate its molecular mechanisms in BDS by integrating metabolomics and bioinformatics. Materials and methods Using a benzene induced BDS mouse model, we analyzed serum-absorbed components of DBD via UPLC-Q/TOF-MS. A multi-omics approach combining metabolomics, molecular docking, and dynamics simulations was utilized to identify therapeutic targets and bioactive components, followed by experimental validation using pharmacological assays, Western blot, and cellular thermal shift assay (CETSA). Results In the BDS mouse model, DBD primarily corrected nicotinate and nicotinamide metabolism and improved hematopoietic function. Furthermore, it significantly decreased the levels of inflammatory cytokines that activate the STAT3 signaling pathway, including interleukin-6 (IL-6), interleukin-17 (IL-17), and transforming growth factor-β (TGF-β). It also suppressed the expression of p-JAK2/JAK2 and p-STAT3/STAT3. Under the effective status of DBD, we identified eleven prototype components and three metabolites derived from DBD, among which astragaloside IV was a high-affinity binder to STAT3, with molecular dynamics simulations and CETSA confirming its binding stability. Conclusion Our integrated approach suggests that DBD may alleviate BDS by normalizing metabolic imbalance and suppressing the IL-6/JAK2/STAT3 signaling pathway. A role for astragaloside IV as a potent bioactive compound of DBD with high-affinity binder to STAT3 is supported by molecular dynamics simulations and CETSA experiments. These findings provide a mechanistic foundation for DBD's therapeutic effects in treating BDS.

Alzheimer’s disease (AD) is a prevalent and progressive neurodegenerative disease characterized by behavioral abnormalities, memory loss, and cognitive decline, presenting significant challenges for early diagnosis and effective treatment. Given the multifactorial pathology of AD and the limited efficacy of conventional approaches, nanotechnology-based strategies have attracted increasing attention as promising solutions to address these unmet clinical needs. Nanomaterials offer distinct advantages for the sensitive and selective detection of AD-related biomarkers due to their high specific surface area, variable surface functions, and capacity to cross biological barriers. This review discusses recent advances in sensing and imaging technologies for AD detection via nanotechnology. Beyond diagnostics, nanomaterials also hold significant therapeutic potential. A variety of nanosystems have been developed to improve drug solubility, promote blood–brain barrier penetration, and achieve controlled or stimulus-responsive drug release. This review presents a comprehensive landscape of recent advances in nano-enabled targeting techniques, with a focus on the target therapy of neuron, microglia, astrocyte, Aβ, Tau, mitochondria and iron. Moreover, the designs of multifunctional nanostructures has enabled synergistic multi-target therapies, which concurrently modulate several pathological pathways. These integrated strategies that integrate antioxidant, anti-inflammatory, anti-aggregative, and neuroprotective mechanisms represent a new paradigm for personalized and precision nanomedicine in AD management.

Damp-heat gout (DHG) is a highly certified type of disease integrated with syndrome in TCM. The ambiguity of its pathomechanism and the lack of quantifiable indicators limit its clinical accurate diagnosis and treatment. This study aimed to elucidate the pathological mechanism of DHG and establish a symptom-centered diagnostic and therapeutic model. We recruited 136 participants, comprising healthy controls (HCs) and DHG patients. Serum metabolomics and proteomics analyses were performed to screen common pathways. Based on the biological significance of these common pathways, a symptom-pathway correlation network was constructed to clarify the pathological mechanisms driving DHG occurrence and progression. Enrichment scores and correlations with key DHG symptoms were used to identify critical pathways. Differential metabolites and proteins associated with these critical pathways served to establish a multi-index diagnostic model and identify potential therapeutic protein targets. Integrated metabolomic and proteomic analyses revealed 21 common pathways associated with DHG. Four crucial pathways, such as Bile secretion, Cholesterol metabolism, Purine metabolism, Arachidonic acid metabolism, were exhibited significant correlations with core DHG symptoms. Furthermore, six pathway-related biomarkers were identified: Hypoxanthine, Prostaglandin E2, Uric acid, Deoxycholic acid, Taurochenodeoxycholic acid, and Bilirubin. The combined diagnostic efficacy of these biomarkers was optimal (discovery cohort: AUC = 0.987; validation cohort: AUC = 0.997). Six protein targets were identified from the crucial pathways, including ATP1A1, APRT, ANGPTL4, GLUT1, PTGES3 and LIPA. This study establishes a symptom-centered diagnostic and therapeutic model for DHG utilizing the identified biomarkers and clarifies the involvement of critical metabolic pathways in DHG pathogenesis, providing novel targets for improved clinical diagnosis and therapy.

The Huangkui capsule (HKC) demonstrates significant efficacy against diabetic nephropathy (DN), yet its bioactive components that exert effects within the target organ, the kidney, have remained poorly characterized. This study aimed to elucidate the renal in situ effective constituents of HKC by integrating multimodal mass spectrometry analyses. A spontaneous DN model was established using db/db mice. Physiological parameters, biochemical indices, and histopathological assessments confirmed the model’s success and the therapeutic effects of HKC intervention. Serum pharmacochemistry based on UPLC-Q-TOF-MS/MS characterized 24 absorbed components. Among them, quercetin, isoquercetin, and their metabolites exhibited the strongest correlation with pharmacodynamic indicators. Crucially, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-TOF-MSI) directly visualized and identified these quercetin-derived conjugates, particularly quercetin glucuronide, within kidney tissues, suggesting their potential as primary in situ bioactive candidates. This study is the first to spatially resolve the kidney distribution of HKC’s active constituents, providing a scientific basis for understanding its mechanism of action and advancing quality control protocols.

Objective: Energy metabolism and immune function have beneficial effects on health. In this study, we demonstrated that early intervention with Jingfang granules (JFGs) promoted energy metabolism and immune function by using an eight-channel energy metabolism detection system and metabolomics techniques combined with physiological and biochemical indicators. Materials and Methods: Male Sprague-Dawley rats were randomly divided into Control, LPS-induced lung injury model, and Jingfang Granules (JFG) intervention groups. Energy metabolism was monitored in freely moving rats using an eight-channel metabolic system), measuring oxygen consumption, carbon dioxide production, and respiratory exchange ratio. Metabolomic profiling was performed using UPLC-Q-TOF/MS chromatography. Physiological and biochemical parameters including inflammatory cytokine levels (TNF-α, IL-6, IL-1β) were assessed by ELISA. Lung histopathology was evaluated through H&E staining following LPS challenge. Results: JFG pretreatment significantly enhanced systemic energy metabolism. Metabolomic analysis revealed JFG-mediated normalization of disrupted metabolic pathways, particularly in amino acid metabolism (valine, leucine, isoleucine degradation) and tricarboxylic acid cycle intermediates. These metabolic improvements correlated with attenuated inflammatory responses, showing significantly reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1β) in JFG-treated animals. Histopathological examination confirmed the protective efficacy of JFG intervention, demonstrating substantially alleviated lung tissue damage, diminished inflammatory cell infiltration, and preserved alveolar architecture following LPS exposure. Conclusions: The experimental results indicated that intervention with JFGs for 1 week could alleviate lung injury in male rats when exposed to lipopolysaccharides.

With immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy emerging as the fourth pillar of cancer treatment, modern oncology has entered a new era. However, clinical challenges—including primary/secondary resistance, limited response rates (particularly in “cold tumors”), and potentially severe immune-related adverse events (irAEs)—significantly constrain their applicability and patient benefit. Traditional Chinese medicine (TCM), grounded in its holistic principles of tonifying the body’s resistance while eliminating pathogenic factors and syndrome differentiation, demonstrates unique scientific value and translational potential through multi-component, multi-target synergistic actions. It remodels the tumor immune microenvironment (TME), enhances antitumor immune responses, and mitigates immunotherapy-related toxicities. This review systematically synthesizes current evidence elucidating core mechanisms by which TCM formulas, single compounds, and bioactive components enhance efficacy and reduce toxicity. Regarding efficacy enhancement, we focus on TCM’s role in reversing T-cell exhaustion, reprogramming tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), inducing immunogenic cell death (ICD), modulating tumor metabolic reprogramming, and optimizing gut microbiota composition to potentiate systemic antitumor immunity. For toxicity reduction, we comprehensively synthesize clinical evidence and pharmacological mechanisms underlying TCM’s mitigation of immune-related pneumonitis, colitis, cardiotoxicity, dermatotoxicity, and myelosuppression. This work establishes a robust theoretical foundation and scientific evidence for novel TCM-integrated strategies in cancer immunotherapy, while outlining future directions in the era of precision medicine.

With increasing environmental pollution and a high incidence of respiratory infections, pulmonary nodules (PN) are being detected more frequently. Although most are benign, they are often accompanied by chronic inflammation and localized fibrosis, which may predispose patients to progression toward idiopathic pulmonary fibrosis (IPF). However, the biological relationship between benign pulmonary nodules (BPNs) and IPF remains poorly understood. Therefore, this study aims to investigate the shared molecular mechanisms and identify potential biomarkers linking BPN and IPF, with the goal of elucidating the pathogenic transition from BPN to IPF. In this study, microarray data from GEO datasets were systematically analyzed to explore shared molecular mechanisms, immune infiltration characteristics, and potential early intervention strategies linking BPN and IPF. Differential expression analysis, protein-protein interaction (PPI) networks, weighted gene co-expression network analysis (WGCNA), and integrative machine learning approaches identified MME and ANKRD23 as key hub genes associated with the transition from BPN to IPF. Both genes demonstrated strong diagnostic performance, with Area Under the Curve (AUC) values exceeding 0.7, and were significantly correlated with immune cell infiltration, particularly effector memory CD8+ T cells. Functional enrichment and gene set enrichment analyses indicated that these genes were mainly involved in immune-related processes in BPN, while in IPF, ANKRD23 was linked to cytoskeletal organization and genomic stability, and MME was enriched in profibrotic pathways such as TGF-β signaling. The diagnostic value of these biomarkers was further validated in a bleomycin-induced IPF mouse model using quantitative polymerase chain reaction (qPCR). In addition, drug-gene interaction prediction and molecular docking analyses highlighted several naturally derived compounds with favorable binding affinity and anti-inflammatory properties, among which folic acid, curcumin, and arbutin emerged as promising candidates for safe early intervention. Collectively, these findings identify MME and ANKRD23 as potential biomarkers for early identification of BPN patients at risk of developing IPF and provide a theoretical basis for early diagnosis and targeted preventive strategies.

Ethnopharmacological relevance Eleutherococcus senticosus fruit (ESF) originates from the mature fruit of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim, which is effective in treating essential hypertension (EH). However, the incomplete comprehension of how ESF antihypertensives impedes its further development. Aim of the study This study aims to elucidate the potential molecular mechanism of ESF in treating EH through network pharmacology, Chinmedomics, molecular docking, and experimental verification. Materials and methods In this study, blood pressure, body weight, organ indices, histopathology, and related kits were employed to systematically evaluate the therapeutic efficacy of ESF on EH. Metabolomics analyzed the core metabolites in serum and urine and delineated the metabolic pathways. Subsequently, an integrated approach combining network pharmacology, Chinmedomics, molecular docking, molecular dynamics simulations, and experimental verification was adopted to elucidate the molecular mechanism underlying the antihypertensive effect of ESF. Results ESF significantly reduced blood pressure, dilated blood vessels, ameliorated oxidative stress, alleviated pathological injuries of the heart and kidney, and reversed the disruption of tryptophan metabolism, taurine and hypotaurine metabolism, vitamin B6 metabolism and other pathways. Chinmedomics combined with network pharmacology identified 5 active constituents targeting 3-hydroxyanthranilic acid oxygenase (3HAO), kynureninase (KYNU), thromboxane synthase (ThrS), sphingosine kinase (SphK), cystathionine γ-lyase (CGL) and pyridoxal 4-dehydrogenase (PLDH). Molecular docking and molecular dynamics simulations verified their stable binding. Furthermore, these components exhibit a synergistic effect. Conclusions This study sheds light on the molecular mechanisms insights underlying ESF treatment of EH, providing a new translational strategy for developing precision therapeutic drugs for EH.

Acute lung injury (ALI) is a severe clinical syndrome with high mortality. Jingfang Granules (JFG), a modern formulation of the traditional Chinese medicine (TCM) compound Jingfang Baidu Powder, has been widely used to treat ALI. However, its protective effects and underlying mechanisms in ALI remain poorly understood. This study is based on a lipopolysaccharide (LPS)-induced ALI rat model, which was intervened with low, medium, and high dose of JFG. We carried out metabolomic analysis and identified 12 blood metabolites, the levels of core metabolites were regulated under JFG intervention, including L-Carnitine, Citric acid, Taurocholic acid, Arachidonic acid (AA), and Linoleic Acid (LA). Besides blood metabolites, 11 urine metabolites were also callback under JFG intervention, including Valine, Citric acid, L-Phenyalalanine, and Leukotriene B4, mainly involving the LA metabolism, AA metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. Comprehensive analysis shows that the restored enrichment pathways are mainly concentrated in inflammatory response, amino acid metabolism, and fatty acid metabolism. These findings reveal the potential mechanism of JFG in LPS-induced ALI, and its pathway nodes facilitate rapid translation from laboratory to clinical applications.

Blood deficiency syndrome (BDS) is a systemic disorder characterized by hematopoietic dysfunction and immune dysregulation. Given the limitations of current therapies, such as single efficacy and adverse effects, there is an urgent need for multitarget therapeutic agents with systemic regulatory effects. In this study, a mouse model of BDS was established through chronic benzene inhalation. Using an integrated transcriptomics and proteomics approach, we systematically investigated the therapeutic mechanism of Danggui Buxue Decoction (DBD). The results demonstrated that DBD significantly restored body weight, thymic and splenic indices, and bone marrow microstructure in model mice but also improved peripheral blood parameters such as the red blood cell count and mean corpuscular volume. Furthermore, DBD coordinately modulated serum hematopoietic factor and inflammatory cytokine levels. Mechanistically, DBD exerts its therapeutic effects through dual pathways. On the one hand, it promotes hematopoietic repair by upregulating transferrin receptor (TFRC) to support iron-dependent erythropoiesis, modulating KITLG/FLT3LG to maintain stem cell pool stability, and reprogramming integrin expression (e.g., upregulating ITGA4 and downregulating ITGA1) to facilitate stem cell homing and suppress fibrosis. On the other hand, it reshapes the immune microenvironment by enhancing MHC class II antigen presentation (e.g., H2Aa, H2-Ab1, H2-DMb1, and H2-Eb1) and immune cell activation (e.g., CD22, CD37, CD20, and CD8a), thereby reestablishing immune homeostasis. This study provides a systematic molecular basis for the multitarget and holistic regulatory properties of DBD, supporting its clinical application and suggesting potential therapeutic targets for BDS-related disorders.

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) was used to comprehensively analyze the chemical components of 20 batches of Alismatis Rhizoma from four production areas and explore the differences in components among them. To accurately identify and characterize the chemical components of Alismatis Rhizoma, principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used to perform multivariate statistical analysis on the Alismatis Rhizoma from production areas: Nanping city in Fujian province, Leshan city in Sichuan province, Pengshan district in Sichuan province, and Qionglai city in Sichuan province. Additionally, analysis of variance was employed to screen the differential chemical components of Alismatis Rhizoma from different origins. A total of 104 chemical components were identified, including 87 triterpenoids, three sesquiterpenes, four organic acids, four amino acids, three flavonoids, and three other components. A total of 18 differential chemical components were characterized, including two unique components and 16 common differential components. Among them, 1S,4S,10S-calamusin Ⅰ was unique to Alismatis Rhizoma produced in Fujian province, and the content of 11,23-dioxo-alisol A and alisolid D was the highest in the Alismatis Rhizoma produced in Nanping city of Fujian province. 24-oxo-25-dehydro-alisol F was unique to Alismatis Rhizoma produced in Sichuan province. The content of 16-oxoalisol A, alisol F, alisol A, alisol G, and alisol M 23-acetate was the highest in the Alismatis Rhizoma produced in Leshan city of Sichuan province. The content of 4-(diglycodylamino) phenyl glycidyl ether, alisol B, alisol L 23-acetate, alisol C 23-acetate, alisol A 23-acetate, alisol O, and 16-oxo-23-acetyl-alisol C was the highest in the Alismatis Rhizoma produced in Pengshan city of Sichuan province, and that of alismanol M and 16-oxo-22-hydroxy-alisol A was the highest in the Alismatis Rhizoma produced in Qionglai city of Sichuan province. In conclusion, the origin of Alismatis Rhizoma has a significant effect on its chemical components. The use of characteristic components can effectively evaluate differences in origin, providing a scientific basis for the quality evaluation and selection of high-quality origins for Alismatis Rhizoma.

ETHNOPHARMACOLOGICAL RELEVANCE:Artemisia capillarisThunb. is a traditional Chinese medicinal herb commonly used in clinical practice for chronic alcoholic liver disease (CALD).Scoparone, one of the major active components of Artemisia capillarisThunb., has emerged as a promising candidate for CALD intervention, yet its mechanism remains unclear. AIM OF THE STUDY:This study aimed to systematically elucidate the pharmacological effects of scoparone and its molecular mechanisms in CALD via multi-omics combined with targeted validation. MATERIALS AND METHODS:The National Institute on Alcohol Abuse and Alcoholism (NIAAA) animal model was established. The NIAAA-established CALD mouse model (chronic ethanol feeding + acute binge, mimicking acute-on-chronic liver injury) was diagnosed via classic clinical methods (liver function biomarkers + histopathology). After validation, scoparone exhibited significant efficacy across different doses. Metabolomics and transcriptomics analyzed urine/tissue samples, with integrated analysis identifying core hubs. Meanwhile, primary hepatocytes were cultured and treated with scoparone. Potential targets were validated via gene knockdown, CETSA, CHX chase, and ubiquitination assays. We used the Seahorse XF Mito Stress Test to evaluate CALD-associated mitochondrial damage and elucidate the key interrelationships. RESULTS:Scoparone normalized serum biochemical indices and liver pathology to near-healthy levels. Urinary metabolomics identified 9 biomarkers, and liver transcriptomics detected 3665 differentially expressed genes.Integrated omics pinpointed the phenylalanine pathway, with TAT/AST co-regulation identified as key. In vitro, primary hepatocytes were cultured with 100 mmol/L ethanol ±25 μmol/L scoparone; CETSA and CHX chase assays confirmed scoparone enhances TAT stability via inhibiting the Ubiquitin-Proteasome pathway. Seahorse analysis showed TAT knockdown-induced hepatocyte apoptosis, oxidative stress, lipid accumulation, and mitochondrial damage were reversed by scoparone or TAT level restoration. CONCLUSIONS:This study first reveals scoparone's novel mechanism in treating CALD: it directly binds tyrosine aminotransferase (TAT), stabilizes its level by inhibiting Ubiquitin-Proteasome-mediated degradation, restores TAT's regulation of phenylalanine to prevent tyrosinemia and associated liver injury or jaundice, and normalizes tyrosine regulation to recover mitochondrial tricarboxylic acid cycle-related pyruvate, reversing oxidative stress and mitochondrial dysfunction.This study validates scoparone as a potential CALD therapeutic and provides robust preclinical data for TAT-targeted therapy.

Rheumatoid arthritis (RA) remains a therapeutic challenge because of the suboptimal efficacy and significant adverse effects of current treatments. Obakulactone (OL), a natural tetracyclic triterpenoid isolated from Phellodendri cortex, has emerged as a promising candidate for RA intervention. However, its underlying mechanism remains poorly understood. In this study, we investigated the therapeutic effects of OL and its molecular mechanisms in RA using a multifaceted approach. A complete Freund’s adjuvant (CFA)-induced RA rat model revealed that OL significantly alleviated joint swelling and restored the expression of CD3+ T cells and CD68+ macrophages in joints, and the polarization state of macrophages shifted from proinflammatory M1 (CD86) to anti-inflammatory M2 (CD206) dominant. In addition, OL alleviated pathological changes in lymphoid organs (thymus and spleen), effectively inhibited the differentiation of CD4+ T cells into T helper 17 (Th17) cells, and normalized serum levels of inflammatory cytokines (e.g., interleukin (IL)-6 and tumor necrosis factor-α (TNF-α)) and RA diagnostic markers (e.g., c-reactive protein (CRP) and rheumatoid factor (RF)). Multiomics profiling revealed that OL corrected the dysregulated biosynthesis and metabolism of unsaturated fatty acids (e.g., arachidonic acid and linolenic acid) in RA rats, with acyl coenzyme A (CoA) thioesterase 1 (ACOT1) identified as a critical regulator. In vitro studies have shown that OL significantly inhibits cell proliferation and inflammatory cytokine secretion and promotes the apoptosis of RA synovial fibroblasts (SFs). It inhibited the M1 polarization of Raw264.7 macrophages and promoted M2 polarization. Mechanistically, cellular thermal shift assays (CETSA), microscale thermophoresis (MST), surface plasmon resonance (SPR), and short hairpin RNA (shRNA) experiments revealed ACOT1 as the direct target of OL. OL enhanced ACOT1 ubiquitination-mediated proteasomal degradation, thereby reducing downstream stearoyl-CoA desaturase-1 expression and inhibiting the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and phosphoinositide 3-kinase (PI3K)–protein kinase B (AKT) signaling pathways, thus suppressing inflammation and fibrosis in SFs. This study establishes OL as a potential RA therapeutic agent and highlights ACOT1 as a novel target for RA intervention, offering insights into fatty acid metabolism reprogramming as a therapeutic strategy.