Arthritis is an inflammatory and immune response in joint involving bone and cartilage that causes bone damage and degeneration, eventually leading to irreversible bone destruction, such as joint deformity. Current clinical treatments primarily focus on anti-inflammatory strategies and regulation of immune tolerance. However, these treatments are often associated with side effects, including infections and immunosuppression, while no existing therapy can fully address these issues. Ginsenosides, as bioactive components in traditional Chinese herbal medicines, can effectively treat arthritis through their anti-inflammatory effects, regulation of metabolism and immunity, and promotion of bone protection and repair. Moreover, the development of interdisciplinary medicine and engineering has facilitated the creation of biomaterials loaded with ginsenosides, which is conducive to improving the bioavailability of ginsenosides and promoting bone formation for the repair of bone damage. This review explores the pharmacological mechanisms of ginsenosides in arthritis treatment and evaluates the current status and limitations of their clinical application. It further discusses combination pathway, mechanism of action, therapeutic advantages and limitations of biomaterials loaded with ginsenosides for arthritis treatment in current stage of basic research. The review aims to summarize the theoretical foundations of ginsenosides in treating various types of arthritis and provide strategies and perspectives for achieving and optimizing their clinical transformation.
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by infertility and menstrual irregularities as primary symptoms, significantly impacting the physical and mental health of women of reproductive age. Due to its complex etiology, there is currently no unified standard treatment for PCOS. With the development of traditional Chinese medicine (TCM) in recent years, many studies have demonstrated its potential therapeutic effects on PCOS. In this review, we summarized the TCM dialectical approach to PCOS, its underlying mechanisms with TCM interventions, and some emerging therapeutic concepts, which are related to multiple signaling pathways. Briefly, TCM can improve PCOS by regulating the hypothalamus-pituitary-ovarian (HPO) axis, improving insulin sensitivity, and exerting anti-inflammatory and anti-oxidative effects, which are related to multiple signaling pathways. In addition, some studies have also suggested that TCM can promote the repair of the ovarian microenvironment and affect related cell signal transduction and proteins to improve PCOS. In summary, this review aims to provide theoretical support and new treatment perspectives for the clinical treatment strategies of PCOS.
Objective Identification of quality marker (Q-Marker) is central to the modernization and quality control of traditional Chinese medicine (TCM). Existing methods, though diverse, lack a unified and scalable strategy to address the chemical and pharmacological complexity of TCM prescriptions. This study established a machine learning-driven framework to integrate multi-source data and systematically prioritize Q-Marker, using Xiaoyao Heji (XYHJ), a modern antidepressant formulation derived from Xiaoyao San, as a case study. Methods Firstly, a dataset of 302 compounds was constructed by summarizing 14 reported Q-Marker discovery strategies and annotated with five core dimensions—compatibility, specificity, measurability, traceability, and effectiveness. Subsequently, five ranking models (RankNet, Random Forest, XGBoost, Linear Regression and K-Nearest Neighbors) were trained with 8-fold GroupKFold cross-validation and evaluated by normalized discounted cumulative gain (NDCG), mean average precision (MAP), and Recall. Thirdly, the optimal model was applied to XYHJ, followed by systematic characterization of chemical profiles, quantitative analysis, drug metabolism and pharmacokinetics (DMPK), quality transitivity, and bioactivity. Finally, Q-Markers were further validated through radar chart modeling, Monte Carlo simulations, and chemometric analyses. Results Through a comparison of the machine learning models, XGBoost outperformed other models, exhibiting high and stable performance with NDCG, MAP, and Recall values ranging from 0.84 to 0.95. For the first time, the XYHJ prescription was comprehensively evaluated across its chemical profile, DMPK properties, quantitative content, manufacturing traceability, and biological efficacy. Using the optimal XGBoost ranking model, 15 components were screened and ranked, successfully identifying paeoniflorin, albiflorin, and glycyrrhizic acid as critical Q-Marker. The reliability of the ranking approach was further validated by integrating a previously published radar chart model with Monte Carlo simulations with over 10 000 sampling iterations. Furthermore, fingerprint similarity and chemometric analysis demonstrated the effectiveness of these Q-Markers in distinguishing XYHJ produced through different manufacturing processes. Conclusion This study developed a machine learning-driven ranking framework that unifies multiple Q-Marker discovery strategies. Using XYHJ as a case study, this approach not only enhances its quality control system but also provides a valuable reference for the standardization and modernization of other TCM prescriptions.
Objective With the advent of the precision medicine era, personalized treatment is becoming an increasingly important trend. However, despite the vast amounts of electronic medical records (EMR) data available, predicting an individual patient’s genetic profile remains a significant challenge. Traditional Chinese medicine (TCM) may provide valuable insights into personalized precision medicine. This study aimed to develop a global prediction of syndrome/phenotype-molecule association within personalization (GPS-MAP) model for personalized syndrome/phenotype-molecule association prediction and to evaluate its potential application in identifying new clinical indications and underlying mechanisms of TCM formulas. Methods GPS-MAP integrates transfer learning, a multi-head mutual-attention mechanism, and large language models (LLMs) for personalized text descriptions. The model was pre-trained on diverse disease/phenotype data and subsequently fine-tuned using a limited TCM syndrome dataset. GPS-MAP was then combined with network target analysis to compare the potential therapeutic advantages of two clinically used TCM formulas and identify potential new clinical subtypes. The computational predictions were further evaluated by clinical Meta-analyses. Finally, in vivo experiments combined with multi-omics analyses were performed to investigate the mechanisms associated with key phenotypes of the newly identified indication. Results GPS-MAP achieved up to a 39.2% improvement in accuracy compared with two widely used TCM syndrome-molecule association prediction tools, SymMap and SoFDA. Using GPS-MAP and network target analysis, this study identified potential advantages of a TCM formula for treating wind-heat syndrome common cold (WHCC) compared with another clinically used formula and identified a new clinical subtype potentially responsive to this formula. Clinical Meta-analyses supported these predictions, demonstrating a significant clinical advantage of the formula in treating WHCC (P < 0.001) and significantly higher efficacy of YQQRT in the newly identified subtype (P < 0.05). Multi-omics analyses from in vivo experiments further indicated that the formula exerted multi-target effects primarily through restoration of immune regulation. Conclusion GPS-MAP provides a framework for personalized syndrome/phenotype-molecule association prediction by integrating transfer learning, attention mechanisms, and LLM-derived textual representations. Its application identified a potentially advantageous treatment and a new clinical subtype, while mechanistic analyses suggested that the associated therapeutic effects involve 14–3-3/forkhead box O1 (FOXO1)-centered signaling and the regulation of immune cell homeostasis, maturation, differentiation, and tracking.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) represent globally prevalent chronic hepatic conditions, in which gut dysbiosis acts as a key pathogenic driver through dysregulation of the gut-liver axis. Herbal medicines (HMs) are increasingly recognized as viable therapeutic candidates for MASLD/MASH, primarily through their ameliorative properties on gut-liver axis and pathophysiological pathways of intestinal microbiota. This review summarizes the pathogenesis of MASLD/MASH and the application of HMs in their treatment from the perspective of the gut-liver axis and intestinal microbiota. The progression of MASLD/MASH involves several pathological processes marked by modifications in the gut-liver axis, including compromised gut barrier function and increased intestinal permeability causing endotoxemia and inflammation, along with alterations in microbiota composition and gut microbiota-derived metabolites. This review further delineates the shared mechanisms within each class of compounds in HMs for ameliorating MASLD/MASH, highlights recent advances in the combined use of HMs and probiotics, and discusses the key issues and challenges associated with the clinical translation of HM-based preparations. These insights potentially catalyze the advancement of novel therapeutics targeting MASLD/MASH, while providing a translational framework for clinical application of HMs.
Objective Ganoderma lucidum is a bioactive-rich traditional Chinese medicine widely recognized for its nutraceutical and pharmaceutical applications. This study optimized the ultrasound-assisted extraction (UAE) from Himalayan G. lucidum, applying artificial-neural network (ANN) modelling coupled with genetic algorithm (GA) optimization to enhance efficiency. Methods The UAE extraction was performed under various process parameters, including treatment duration (i1, 5–15 min), ultrasonic amplitude (i2, 30%−80%), and solvent concentration (i3, 40%−80%), to optimize the yield (w/w%, O1), total triterpene content [mg/g, dry weight (dw), O2], 2,2-diphenyl-1-picrylhydrazyl scavenging activity (%, O3) and total phenolic content (mg/g dw, O4). Results The ANN-GA approach accurately modeled the complex non-linear relationships between input and output parameters, identifying optimal conditions as 5 min (i1), 45.63% (i2) and 80% (i3). Experimental validations under these conditions resulted in (7.63 ± 0.2) %, (34.11 ± 0.01) mg/g dw, (41.55 ± 0.01) % and (10.98 ± 0.01) mg/g dw for O1, O2, O3, and O4 respectively. Compared to response surface methodology (RSM) approach, which served only as a benchmark, the ANN-GA approach demonstrated superior predictive accuracy and robustness in optimization. Conclusion The ANN-GA approach provides an effective and robust strategy for optimizing herbal extraction processes. This study demonstrates the applicability of ANN-GA as an advanced optimization tool for herbal extraction processes and highlights G. lucidum as a valuable source of natural antioxidants and triterpenes with potential therapeutic relevance.
Objective Doxorubicin (DOX) remains a cornerstone chemotherapy for triple-negative breast cancer (TNBC), but its efficacy is limited by tumor resistance and aberrant lipid metabolism. This study investigates whether berberine and rhein—active components of the traditional Chinese medicine formula Dahuang Huanglian Xiexin Decoction—can enhance DOX efficacy in TNBC by modulating lipid metabolism. Methods This study developed a berberine and rhein liposomal formulation (BR-lipo) co-encapsulating berberine and rhein to improve their solubility and bioavailability. The combination of BR-lipo and DOX was evaluated in a 4 T1 mouse model of TNBC. Tumor growth and lung metastasis were monitored, while lipid metabolism alterations were assessed using Oil Red O staining, spatial metabolomics, and transcriptomic analysis. Results BR-lipo significantly enhanced the antitumor effect of DOX, suppressing both primary tumor growth and lung metastasis in 4 T1-bearing mice. Oil Red O staining revealed reduced lipid droplet accumulation in tumor tissues. Spatial metabolomics showed decreased monounsaturated fatty acids (MUFAs), potentially through inhibition of stearoyl-CoA desaturase 1 (SCD1). Transcriptomic analysis indicated downregulation of peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of lipid metabolism. These findings were consistent across both in vivo and in vitro experiments. Conclusion Berberine and rhein delivered via liposomal formulation effectively modulate TNBC lipid metabolism, potentially through the PPARγ-SCD1 axis, and sensitize TNBC to DOX chemotherapy. This study provides a novel strategy to overcome DOX resistance in TNBC by targeting lipid metabolic pathways.
Objective Erchen decoction (ECD) is documented in “Formulary of the Bureau of Taiping People’s Welfare Pharmacy” as having therapeutic effects on lipid disorders through multiple targets and pathways. However, the underlying mechanisms of ECD in atherosclerosis (AS) treatment remain to be elucidated. Methods UPLC-Q-E-Orbitrap-MS was used to identify the active ingredients of ECD and the ECD-containing serum (ECDS). Active ingredients identified from the ECDS were used in network pharmacology to predict potential therapeutic targets of ECD in AS, followed by molecular docking and molecular dynamics simulation to evaluate their binding affinities with adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPARγ), liver X receptor alpha (LXRα), and ATP-binding cassette transporters A1 and G1(ABCA1/G1) proteins. In vivo, the efficacy of ECD against AS was assessed via blood lipid analysis, inflammatory biomarker analysis, and histopathological staining of the aorta. In vitro, a foam cell model was established using mouse primary peritoneal macrophages, and Oil Red O staining, Western blotting, and cholesterol efflux assays were performed to investigate the effects of ECD on cholesterol metabolism. Pharmacological inhibitor experiments were used to elucidate regulatory effects of ECD on the AMPK-mediated PPARγ/LXRα/ABCA1/G1 signaling pathway. Results A total of 37 active ingredients were identified in the ECDS. Network pharmacology analysis indicated that ECD primarily regulated inflammation-related pathways and modulated cholesterol metabolism through the AMPK and PPAR signaling pathways, targeting key lipid metabolism targets, such as PPARA and PPARG. Molecular docking revealed favorable binding affinities between multiple ECDS ingredients and the AMPK, PPARγ, LXRα, and ABCA1/G1 proteins, with the five strongest protein–ligand pairs being AMPK-liquiritin apioside, PPARγ-narirutin, LXRα-apioglycyrrhizin, ABCA1-apigenin-7-O-glucoside, and ABCG1-hesperidin. Molecular dynamics simulation further validated the docking results. In vivo, ECD attenuated AS progression, as evidenced by decreased lipid levels, reduced expression of inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and −IL-1β, diminished relative en face aortic lesion area, plaque area, lipid accumulation, macrophage infiltration, and increased collagen content in plaques. In vitro, the ECDS reduced the formation of macrophage-derived foam cells by promoting cholesterol efflux. In terms of the specific mechanism, both in vivo and in vitro pharmacological inhibitor experiments confirmed that the therapeutic effects of ECD on AS were mediated via the AMPK-mediated PPARγ/LXRα/ABCA1/G1 signaling pathway. Conclusion This research indicated that ECD effectively attenuated AS progression by targeting the AMPK-mediated PPARγ/LXRα/ABCA1/G1 signaling pathway, providing new insights into the anti-AS mechanisms of ECD.
Objective Changyanning Granule (CYNG) is a classic Chinese patent medicine that treats gastrointestinal disorders, however, its mechanism of action is unclear.This study investigated the protective effect of CYNG on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice and explored its mechanisms of action. Methods A mouse colitis model was established using 3% DSS. Disease activity was assessed by disease activity index (DAI). Histopathological changes were evaluated by hematoxylin-eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) staining. Intestinal barrier function and inflammation were examined via immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), oxidative stress assays, reverse transcription polymerase chain reaction (RT-qPCR), and Western blotting (WB). Gut microbiota composition, short-chain fatty acid (SCFA) levels, and fecal metabolomic profiles were analyzed by 16S rRNA sequencing, targeted SCFA detection, and metabolomics, respectively. Results CYNG treatment significantly alleviated the symptoms of colitis, as evidenced by a decrease in DAI, and it also improved the colonic pathological damage in UC mice induced by DSS. Moreover, CYNG effectively restored the intestinal barrier function and alleviated colonic inflammation. Mechanistically, CYNG regulated the mitogen-activated protein kinase (MAPK) pathway by inhibiting the expression of p-p38 and p-JNK proteins. Furthermore, CYNG exerted protective effects by maintaining intestinal flora homeostasis, modulating SCFA and regulating amino acid metabolic. Conclusion CYNG effectively ameliorates DSS-induced ulcerative colitis via a synergistic mechanism involving the regulation of MAPK inflammatory signaling, gut microbiota and related metabolic disorders. These findings support the treatment of UC with CYNG.
The imbalance between the increasing global prevalence of liver disease and the limited availability of effective drugs highlights the need to develop novel hepatoprotective ingredients. Medicinal fungal polysaccharides (MFPs) have shown promise as hepatoprotective agents owing to their diverse liver-beneficial activities. This review summarizes decade-long advancements in hepatoprotective MFPs studies, including their sources, preparation technologies, chemical structures, hepatoprotective properties and mechanisms, as well as the existing research challenges. A total of 61 hepatoprotective MFPs from 18 species of medicinal fungi have been identified in the past decade. Various advanced techniques for MFPs preparation and characterization are well-established at the laboratory scale. MFPs exhibit hepatoprotective potential through diverse mechanisms in various liver disorders. MFPs offer a promising avenue for the development of scarce hepatoprotective agents, but there are still many challenges to translate the laboratory studies of MFPs into practical applications, including the lack of efficient standard preparation methods for large-scale industrial, lagging standardization and quality control of MFPs, unelucidated systemic biological effects of hepatoprotective MFPs and insufficient market acceptance and awareness of MFPs. Addressing these challenges is expected to facilitate the transition of MFPs from experimental innovation to clinical or commercial application, ultimately benefiting patients with liver disease worldwide.
Objective This study aims to develop an eco-efficient deep eutectic solvent (DES)-based extraction protocol for Ginkgo biloba leaf polysaccharides (GBLPs) by optimizing solvent composition and operational parameters, achieving high-yield isolation of structurally intact GBLPs to support their antioxidative, anti-inflammatory, and neuroprotective applications. Methods Using choline chloride as a hydrogen bond acceptor and alcohols, acids and amides as hydrogen bond donors, a variety of DESs were prepared. The design of experiments was optimized using the single-factor method. Then the best extraction condition was determined by response surface analysis. The microstructure of G. biloba leaves powder before and after extraction with extraction with ultrasound-assisted water extraction (UAE-water) and ultrasound-assisted DES extraction (UAE-DES) was investigated by scanning electron microscope (SEM) to further elucidate the potential mechanism of polysaccharide extraction from G. biloba leaves. The monosaccharide composition of GBLPs was analyzed by the 1-phenyl-3-methyl-5-pyrazolone (PMP) pre-column derivatization method. The molecular weight distribution of GBLPs was determined by gel permeation chromatography-refractive index-multiangle laser light scattering (GPC-RI-MALS) The antioxidant activities of GBLPs have also been studied. Results The optimized extraction protocol employed a choline chloride-propanedioic acid DES (3:1 M ratio) with 30 % water content, achieving a polysaccharide yield of (31.76 ± 0.45) mg/g at 32 ℃ using a 29: 1 mL/g liquid–solid ratio. This DES system demonstrated superior extraction efficiency compared to conventional solvents. GBLPs is a typical acidic heteropolysaccharide, wherein Glc and GlcA constitute the predominant monosaccharide components. The Mw, Mn, and Mz of GBLPs were calculated to be 122.613, 58.477, and 178.446 kDa, respectively. In vitro antioxidant experiments show that the DES extract of G. biloba leaves has significant antioxidant activity. Fourier transform infrared spectroscopy (FT-IR) spectral analysis confirmed successful DES formation. SEM micrographs revealed structural disintegration of ginkgo leaf particles after DES treatment directly correlating with enhanced polysaccharide release efficiency. Conclusion This study established an environmentally friendly and efficient extraction process and successfully applied it to extract polysaccharides from G. biloba leaves. The experimental results showed that this method has significant application potential and provides a new research idea for extracting the active components of G. biloba leaves.
Objective Hyperlipidemic acute pancreatitis (HLAP) is becoming increasingly common, and the progression of the disease is more severe, commonly associated with persistent multiorgan failure. Zexie Decoction (ZXD), which consists of Alismatis Rhizoma (Zexie in Chinese) and Atractylodis Macrocephalae Rhizoma (Baizhu in Chinese), has anti-inflammatory and lipid-lowering activity. However, the mechanisms remain unknown. Therefore, this study aims to investigate the effects of ZXD on HLAP and HLAP-related liver injury and elucidate the underlying mechanisms. Methods This study first established sodium taurocholate (STC)-induced acute pancreatitis (AP) and high-fat diet (HFD)-STC-induced HLAP rat models. AR42J cells, the rat pancreatic exocrine cells, were stimulated with palmitic acid (PA) and STC and cultured with ZXD. Then, network pharmacology was employed to predict possible mechanisms of ZXD in protecting against HLAP. Serum was collected to detect total cholesterol (TC), triglycerides (TG), amylase (AMY), lipase (LPS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-6 (IL-6), and interleukin-1β (IL-1β) to assess the influence of ZXD on the pancreas and liver and AR42J cell supernatant was used to detect AMY, IL-6 and IL-1β to evaluate the improvement effect of ZXD on AR42J. In addition, liver and pancreas tissue samples and AR42J cells were taken to study histological assessment, oxidative stress, mitochondrial function, autophagy, and apoptosis using hematoxylin-eosin staining (H&E), Oil red O staining, immunofluorescence staining, and Western blotting. Results It was confirmed that mitochondria and endolysosomal-autophagy system were damaged in both AP and HLAP models. ZXD significantly attenuated systemic inflammation in HLAP rats, reducing TC, TG, AMY, LPS, AST, ALT, IL-6, IL-1β, and ZXD significantly reduced the AMY, IL-6 and IL-1β levels of AR42J cells. Meanwhile, ZXD improved histopathological damage, decreased oxidative damage, reversed excessive mitochondrial fission, promoted mitophagy and autophagy, and facilitated apoptosis in liver tissue and AR42J cells. Conclusion The findings revealed that ZXD alleviated HLAP by improving mitochondrial function, restoring autophagic flux, and promoting apoptosis, which provided new ideas for developing therapeutic drugs for HLAP.
Objective Nonalcoholic fatty liver disease (NAFLD) is a continuum of liver abnormalities from nonalcoholic fatty (NAFL) to nonalcoholic steatohepatitis (NASH), which has become a major public health problem worldwide. Zexie Decoction (ZXD), a traditional Chinese formula derived from Synopsis of the Golden Chamber, has been reported to have the effects of lowing hyperlipidemia and ameliorating NAFLD. Nevertheless, the underlying mechanism by which ZXD alleviates NAFL and NASH remains elusive. This study aims to explore the therapeutic role of ZXD in the process of NAFLD and elucidate the mechanism by which ZXD maintains lipid homeostasis in vivo and in vitro so as to provide a potential candidate for clinical treatment of NAFLD. Methods NAFL and NASH mice models introduced by high fat and high cholesterol diet (HFHCD) or methionine and choline deficient diet (MCD) were established and used to investigate the benefits of ZXD on the progress of NAFLD in vivo. Human hepatocellular carcinoma cell line (HepG2) and mouse alpha liver 12 cell line (AML12) were stimulated by oleic acid and palmitic acid (OPA) to induce lipid accumulation model in vitro. The levels of total cholesterol (TC), triglyceride (TG), nonesterified free fatty acids (NEFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) were measured by commercial kits. Hematoxylin and eosin (HE) staining, Oil Red O staining, Sirius red staining and immunofluorescence staining were applied to observe the liver lesions such as steatosis, inflammation, and fibrosis. Levels of interleukin-1β (IL‑1β), IL-6 and tumor necrosis factor-α (TNF‑α) were detected by ELISA. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis were conducted to detect the related mRNA and protein levels after ZXD intervention in both mice liver and hepatocytes. Results In vivo, ZXD ameliorated hepatocellular steatosis and hepatocellular ballooning in NAFL mice. Additionally, ZXD affected lipid accumulation, inflammation and fibrosis in mice with NASH. Compared with the control group, HFHCD and MCD diets can downregulate phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl CoA carboxylase (p-ACC) and carnitine palmitoyltransferase 1 (CPT1) protein levels, upregulate sterol regulatory element-binding protein 1c (SREBP-1c) and cluster of differentiation 36 (CD36) protein levels, and also increase TC, TG, AST, ALT, ALP levels in mice liver. ZXD could reverse these changes significantly. Besides, ZXD could significantly reduce mRNA levels of Srebp-1c, Fasn, Acc1, Cd36 and increase the levels of peroxisome proliferator activated receptor alpha (Pparα) and Cpt1 after HFHCD and MCD diet stimulation. In vitro, ZXD could increase mitochondrial membrane potential, ameliorate lipid accumulation by inhibiting the synthesis and uptake of fatty acid, while promoting fatty acid oxidation. These results suggest that the therapeutic effect of ZXD on NAFLD may be related to the phosphorylation of AMPK, activation of target protein such as ACC and CPT1, and inhibition of SREBP-1c and CD36. Conclusion ZXD could be a promising natural medicine for the treatment of NAFL/NASH and related diseases.
Objective Pancreatic cancer (PC) is highly lethal and resistant to current therapies, underscoring the need for novel strategies that target regulated cell death. This study aimed to evaluate the anti-PC efficacy of total secondary saponins (TSS) from Anemone raddeana and elucidate the mechanism by which TSS induces pyroptosis. Methods TSS components were characterized by mass spectrometry. Anti-tumor effects were assessed in vitro using human pancreatic cancer cell lines (PANC-1 and AsPC-1 cells) and in vivo using xenograft mouse model. Integrated multi-omics analyses (network pharmacology, proteomics, metabolomics, bioinformatics) identified core components, targets, and pathways. Key findings were validated by molecular docking, immunohistochemistry, and Western blotting. Results Mass spectrometry identified 17 C-3 monosaccharide triterpenoid saponins in TSS. Both in vitro and in vivo models confirmed that TSS can significantly inhibit PC cell proliferation by inducing pyroptosis through the Caspase-3/gasdermin E (GSDME) pathway. Multi-omics highlighted hederacolchiside A1 as a core compound and revealed its regulation of inflammation, proliferation, and oxidative stress through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and nuclear factor-κB (NF-κB) signaling pathways. Molecular docking and Western blotting analysis confirmed activation of downstream pyroptosis mechanisms. Conclusion This study demonstrates that TSS suppresses PC progression by regulating Caspase-3/GSDME-mediated pyroptosis through modulation of PI3K/Akt and NF-κB signaling pathways, supporting its potential as a novel therapeutic candidate for PC.
Medicinal plants are indispensable resources for traditional medical systems and natural product-based drug discovery. However, domestication and intensive breeding have reduced their genetic diversity and the complexity of their associated microbiomes, thereby limiting adaptability and stable production. Microbiome-based precision breeding provides a promising strategy for developing ideal medicinal plant (IPM) phenotypes characterized by high yield, high resistance, and high content of bioactive compounds. The composition, functions, and assembly mechanisms of plant-associated microbiomes are first summarized, followed by an evaluation of the current progress and limitations of precision agriculture microbiome engineering (PAME) in breeding programs. On this basis, a novel framework termed herb-microbiome interaction breeding (HMIB) is proposed. This framework emphasizes the mechanisms by which multilayer genetic regulation, including chromosomally encoded genes, cytoplasmic genetic factors, and microRNA-mediated regulation, shapes plant-associated microbiomes. Rational strategies for designing microbial inoculants are further discussed, including synthetic communities (SynComs), as well as the application potential of microalgae, nanomaterials, and prebiotics in constructing functional microbial inoculant systems. Finally, current challenges and future directions for the HMIB strategy in advancing the sustainable development of IPM are discussed.
Objective Crystals of monosodium urate (MSU) are the cause of gout, a common inflammatory disease. Parthenolide (Par), sesquiterpene lactone, derived from feverfew (Pyrethrum parthenium), possesses potent analgesic, anti-inflammatory, and anticancer properties. However, it remains elusive whether and how Par modulates gout. This research was designed to explore the therapeutic effect and mechanism of Par in acute gout. Methods Chondrocytes from rat knee joint and mouse peritoneal macrophages (MPMs) were stimulated by lipopolysaccharide (LPS) plus MSU. Combination of yeast extract (YE) with oxygen oxyazine (OXO) was administered to mice to simulate hyperuricemia. MSU crystals were injected into the mice’s paws or subcutaneously into the mice’s backs to establish acute gouty models. Results Par blocked the activation of NOD-Like Receptor Pyrin Domains 3 (NLRP3) inflammasome by reducing the expression and release of inflammatory mediators in gouty mice and LPS plus MSU-stimulated MPMs, LPS plus MSU-stimulated chondrocytes as well. Par also promoted phagocytosis abilities of MPMs and chondrocytes to reduce inflammation. In addition, Par dose-dependently reduced the serum levels of uric acid (UA), xanthine oxidase (XOD), creatinine (CRE), and blood urea nitrogen (BUN) and ameliorated renal injury in mice with hyperuricemia. Conclusion Par ameliorated uric acid metabolism disorders of hyperuricemia, and improved acute gout-like inflammation through the inhibition of NLRP3 inflammasome activation, indicating that Par may be a promising candidate for gout-targeted therapy.
Trace elements in traditional Chinese medicine (TCM) constitute a fundamental material basis underlying its pharmacological effects. Although present in extremely low concentrations, these elements are indispensable for maintaining physiological homeostasis and human health. Elemental traditional Chinese medicine (ETCM) integrates TCM theory with elemental medicine, coordination chemistry, systems biology, and other interdisciplinary fields. The core objective of ETCM is to elucidate the material basis and mechanism of action of TCM at the elemental level. ETCM demonstrates that the specific speciation, concentrations, and combinations of elements are critical determinants of pharmacological efficacy, while also revealing the mechanistic associations between elemental homeostasis and disease pathogenesis. Furthermore, ETCM promotes the transition of TCM research from conventional static analyses of elemental content toward dynamic investigations of elemental speciation, bioavailability, metabolic interactions, and systemic biological networks. This approach provides a new perspective for elucidating the material basis of pharmacological efficacy and offers novel pathways for the development of metallopharmaceuticals and the modernization of TCM.
Objective Myocardial fibrosis drives the progression of various cardiovascular diseases and causes heart failure and death, largely due to the activation and myofibroblastic differentiation of cardiac fibroblasts. Phosphoglycerate mutase 1 (PGAM1) interacts with actin alpha 2, smooth muscle (ACTA2) to regulate myocardial fibrosis, and disrupting this interaction can alleviate fibrotic lesions. However, novel natural product-derived PGAM1 ligands targeting this axis remain unidentified. To address this gap, this study aimed to screen and identify novel PGAM1 ligands from a natural product library for potential anti-fibrotic application. Methods Drug affinity responsive target stability (DARTS) and in silico screening were used to identify promising ligand in Carthami Flos. Cellular thermal shift assay (CETSA), DARTS, molecular dynamics simulation and bio-layer interferometry assays were performed for target identification. Furthermore, the cardioprotective effects against myocardial fibrosis were assessed in transforming growth factor-β1 (TGF-β1)-induced cardiac fibroblasts and in mouse transverse aortic constriction (TAC) or isoproterenol-induced fibrosis models. Western blotting, quantitative real-time polymerase chain reaction, immunoprecipitation and immunofluorescent were performed to confirm the antifibrosis mechanism of baicalin. Results Firstly, various natural products were screened via DARTS assay and Carthami Flos was identified as a target pool for molecular docking. Then, in silico screening assay identified baicalin as a novel ligand. In addition, baicalin could directly bind to the PGAM1 protein with a equilibrium dissociation constant (KD) value of 34.6 μmol/L. Molecular dynamics simulation revealed that baicalin and PGAM1 interactions were stable. These findings indicate that PGAM1 is a direct pharmacological target of baicalin. Furthermore, molecular mechanism exploration reveals that baicalin exerts anti-myocardial fibrosis effects by inhibiting the activation of fibroblasts, the interaction between PGAM1 and ACTA2. Finally, the anti-myocardial fibrosis effect of baicalin was verified in vivo. Conclusion These findings suggest that baicalin is a novel PGAM1 templates for developing new therapeutics against myocardial fibrosis.
Globally, gastric cancer (GC) is a very common and deadly malignant tumor. Inflammatory storms in the stomach trigger gastric carcinogenesis, with bacterial infection, obesity, lifestyle, and bile reflux playing crucial roles in GC development and treatment. Modern molecular biology has revealed the vital roles of inflammation-associated signaling pathways, including nuclear factor-κB (NF-κB), interleukin-11/janus kinase 2 and signal transducer and activator of transcription 3 (IL-11/JAK2/STAT3), cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING), and cyclooxygenases-2 (COX-2)/prostaglandin E2 (PGE2), in GC development and treatment. Furthermore, effective anti-inflammatory strategies can delay or prevent GC onset and improve the efficacy of conventional therapeutics. Nevertheless, the GC risk factors, signaling pathways, and crosstalk between inflammation in GC are vaguely understood. Herein, we reviewed the pathogenic factors and internal mechanisms of GC development from an inflammatory perspective and presented key promising developments in anti-inflammatory strategies, emphasizing on traditional Chinese medicine and its active ingredients for GC. These advances provide insights into a theoretical basis for the application of anti-inflammatory strategies for GC prevention, diagnosis, and treatment.
