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This study aims to investigate the effect and mechanism of the EtO Ac extract of Draconis Sanguis(DSE) on improving athero sclerosis in ApoE gene knockout(ApoE~(-/-)) mice. The ApoE~(-/-) mice were randomly divided into five groups: control group, mo delgroup, positive group treated with ezetimibe of 5 mg·kg~(-1)(EG), and low(100 mg·kg~(-1)) and high dose(200 mg·kg~(-1)) groups ofDSE. xcept for the control group, all other groups were fed a high-fat diet and administered drugs for 16 successive weeks. After 16 weeks of Eadministration, the body weight, liver, and epididymal fat mass of the mice were measured; the level of blood lipid and the plaquearea of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo. In addition, in vitro cultures of human umbilical v ein endothelial cell(HUVEC) were conducted. Oxidative stress of endothelial cells was induced by oxidized low-density lipoprot ein(ox-LDL), and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined. The results sho wedthat both doses of DSE significantly improved the epididymal fat mass and index of ApoE~(-/-) mice with atherosclerosis, lowered thelevels of plasma cholesterol, triglyceride, and non-high density lipoprotein cholesterol, and reduced the plaque area of the aortic ou tflow tract. totIn alvitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVECcells, confirming that DSE improved the degree of atherosclerotic lesions in ApoE~(-/-) mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.
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Apolipoproteínas E , Aterosclerosis , Ratones Noqueados , Animales , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética , Aterosclerosis/metabolismo , Ratones , Apolipoproteínas E/genética , Masculino , Humanos , Estrés Oxidativo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Lignanamides are a class of compounds containing amide functional groups in lignans. These compounds have excellent anti-inflammatory and neuroprotective, which have shown great potential in terms of food additives, medicine and health supplement. We summarized the recent progress of lignanamides, including chemical constituents, extraction methods, biological activities, and synthetic pathways. The structures were classified according to an updated nomenclature system, can be classified into sixteen types and have certain roles in many respects such as anti-inflammatory, anti-cancer, and antioxidative, which may be important source of materials for functional food. The potential and limitations of different extraction method, chromatographic packing, and synthetic pathway are analyzed. Notably, this review provides an overview of synthesis pathways and applications of lignanamides, further research is needed to improve extraction efficiency and synthesis method, especially in a greener way for better application.
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The human malaria parasite Plasmodium falciparum (P.â falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti-P.â falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P.â falciparum. Our results reveal that ubiquitin carboxyl-terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6' region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P.â falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti-malarial agents in the future.
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Heterojunctions play a crucial role in improving the absorption of visible light and performance of photocatalysts for organic contaminants degradation in water. In this work, a novel type-II-II Ag2CO3/Bi2WO6 (AB) heterojunction was synthesized by hydrothermal reaction and in situ-precipitation methods. The mechanisms of charge transfer and carrier separation at the interface of heterojunctions and the influence on the photocatalytic activity were investigated. The degradation of levofloxacin (LEV) under visible light irradiation was employed to evaluate the photocatalytic performance of AB. The results showed that 85.4% LEV was degraded by AB, which was 1.38 and 1.39 times higher than that of Bi2WO6 and Ag2CO3, respectively. The work functions of the different crystal planes in the AB heterojunction, which was calculated by density functional theory, are a significant difference. The Fermi energy (Ef) of Ag2CO3 (- 6.005 eV) is lower than Bi2WO6 (- 3.659 eV), but the conduction band (CB) is higher. Therefore, using AB heterojunctions as an example, the research explored the mechanism of type-II-II which CB and Ef of one semiconductor cannot simultaneously surpass those of another material, based on the built-in electric field theory. Through this analysis, a deeper understanding of type-II heterojunctions was achieved, and providing valuable insights into the behavior of this specific heterojunction system.
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Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 µM, with inhibition ratios ranging from 5.1% to 14.3%.
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Alcaloides , Fritillaria , Raíces de Plantas , Fritillaria/química , Raíces de Plantas/química , Estructura Molecular , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Cevanas/química , Cevanas/farmacología , Cevanas/aislamiento & purificación , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Animales , Conformación Molecular , Cristalografía por Rayos X , Línea Celular , Ratas , Esteroides/química , Esteroides/aislamiento & purificación , Esteroides/farmacología , Relación Dosis-Respuesta a Droga , Relación Estructura-Actividad , Modelos MolecularesRESUMEN
In this paper, an alumina ink with good rheological properties was successfully prepared using pseudoboehmite as the main component, nitric acid as the colloidal solvent, and sesbania powder as the lubricant. The impact of nine different ink formulations, namely, Ink1 to Ink9, on the printability and rheological features of the ink was investigated. Consequently, it was found that Ink3 with 5 wt % nitric acid and 5 wt % sesbania powder exhibited the most favorable formability. This ink was utilized to fabricate alumina samples with direct ink writing (DIW) three-dimensional (3D) printing technology. The printed alumina samples were characterized using an automatic Brunauer-Emmett-Teller, X-ray diffractometer, Fourier transform infrared spectroscopy, and scanning electron microscope. To obtain the optimal printing parameters, a three-factor and three-level orthogonal test was designed to research the influences of different 3D printing parameters (filling ratio, nozzle diameter, and layer thickness) on the specific surface area, pore characteristics (size and volume), and radial crushing strength of the alumina specimens. The primary and secondary orders of the effects on the radial crushing strength and pore structure were determined through analysis of the experimental data. The experimental results showed that the alumina sample with a filling ratio of 80%, nozzle diameter of 0.6 mm, and layer thickness of 0.3 mm was found to have better strength of 48.07 ± 9.53 N/mm and specific surface area of 185.7315 m2/g. This study provides a theoretical base for the preparation of alumina carriers by DIW 3D printing.
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Fibroblast-like synoviocytes (FLS) play an important role in rheumatoid arthritis (RA)-related swelling and bone damage. Therefore, novel targets for RA therapy in FLS are urgently discovered for improving pathologic phenomenon, especially joint damage and dyskinesia. Here, we suggested that pyruvate kinase M2 (PKM2) in FLS represented a pharmacological target for RA treatment by antimalarial drug artemisinin (ART). We demonstrated that ART selectively inhibited human RA-FLS and rat collagen-induced arthritis (CIA)-FLS proliferation and migration without observed toxic effects. In particular, the identification of targets revealed that PKM2 played a crucial role as a primary regulator of the cell cycle, leading to the heightened proliferation of RA-FLS. ART exhibited a direct interaction with PKM2, resulting in an allosteric modulation that enhances the lactylation modification of PKM2. This interaction further promoted the binding of p300, ultimately preventing the nuclear translocation of PKM2 and inducing cell cycle arrest at the S phase. In vivo, ART obviously suppressed RA-mediated synovial hyperplasia, bone damage and inflammatory response to further improve motor behavior in CIA-rats. Taken together, these findings indicate that directing interventions towards PKM2 in FLS could offer a hopeful avenue for pharmaceutical treatments of RA through the regulation of cell cycle via PKM2 lactylation.
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Artritis Reumatoide , Proliferación Celular , Sinoviocitos , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Sinoviocitos/patología , Artritis Reumatoide/patología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Humanos , Ratas , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Piruvato Quinasa/metabolismo , Proteínas de Unión a Hormona Tiroide , Masculino , Hormonas Tiroideas/metabolismo , Artritis Experimental/patología , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Movimiento Celular/efectos de los fármacos , Terapia Molecular Dirigida , Proteínas de la Membrana/metabolismo , Proteínas Portadoras/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/químicaRESUMEN
BACKGROUND: Cayratia albifolia C.L.Li (CAC), commonly known as "Jiao-Mei-Gu" in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot. RESULTS: CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA. CONCLUSIONS: We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation.
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OBJECTIVE: Poor fetal and perinatal outcomes in fetuses associated with umbilical artery thrombosis (UAT), such as severe intrauterine growth restriction (IUGR) and intrauterine asphyxia have been reported by some case series. Its hemodynamic impact remains unclear. The aim of this study was to evaluate the hemodynamic changes and perinatal outcome in UAT fetuses with a relatively large sample. METHODS: We included singleton fetuses diagnosed with UAT and with at least one available Doppler evaluation before the end of pregnancy in our center from 2016 to 2023. Fetuses with structural abnormalities and with no follow-up results were excluded. Doppler waveforms from the Umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and uterine artery (UtA) were routinely evaluated according to ISUOG Practice Guidelines from diagnosis. The same sample of GA-matched normal fetuses with Doppler measurements during the same period were randomly selected as control group. RESULTS: Eighty-nine singleton fetuses with UAT with at least one Doppler evaluation before the end of pregnancy were identified, 13 fetuses with no follow-up results were excluded. After comprehensive prenatal counseling, 14 cases received urgent cesarean section, the remaining 55 cases received expectant management, the median day between GA at diagnosis and end of pregnancy was 13 (5-53) days (range, 2-159). 7 (7/76, 9.2%) cases occurred stillbirth, and the incidence of IUGR and Neonatal Intensive Care Unit (NICU) admission were 18.4% (14/76) and 13.2% (10/76) respectively. 49 fetuses (49/76, 64.5%) combined with Doppler abnormalities. UA abnormalities (35/76, 46.1%) and MCA abnormalities (34/76, 44.7%) were the most changes at presentation. Compared to control group, UA-EDV was significantly increased in UAT fetuses [21.84 (15.59-26.64) vs. 16.40 (12.43-20.70) cm/s, p < 0.001], UA-PI and UA-RI significantly decreased [0.68 (0.57-0.84) vs. 0.92 (0.79-1.11), p<0.001; 0.51 (0.44-0.59) vs. 0.62 (0.55-0.68), p < 0.001, respectively]. Both the MCA-PSV and MCA-EDV were significantly higher in UAT fetuses [54.60 (48.00-61.34) vs. 44.47 (29.66-57.60) cm/s, p < 0.001; 11.19 (7.84-17.60) vs. 8.22 (5.21-12.00) cm/s, p < 0.001, respectively], this led to a lower MCA-PI and MCA-RI. Meanwhile, DV-PIV was significantly higher in UAT fetuses [0.6 (0.47-0.87) vs. 0.45 (0.37-0.55), p < 0.001], CPR and UtA-PI were no significant difference between these two groups. Multivariate logistic regression analysis showed that DV-PIV was an independent risk factor for adverse pregnancy outcomes (OR 161.922, p<0.001), the area under the ROC curve (AUC) was 0.792 (95% CI 0.668-0.917; p < 0.001). CONCLUSION: Our data showed serious adverse pregnancy consequences are combined with UAT fetuses. Hemodynamic changes in UAT fetuses showed the remaining artery for compensation and brain perfusion derangement. With a comprehensive and standardized Doppler evaluation, progression of fetal deterioration may be detailed presented.
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Trombosis , Arterias Umbilicales , Recién Nacido , Embarazo , Humanos , Femenino , Arterias Umbilicales/diagnóstico por imagen , Estudios Retrospectivos , Cesárea , Feto , Retardo del Crecimiento FetalRESUMEN
Adhesive small bowel obstruction (ASBO) causes a major burden in emergency medicine. Owing to in situ decompression, nasointestinal tube (NIT) placement has been increasingly used in clinical practice compared with traditional conservation (TC); however, the indications remain controversial. This study was designed to explore the indications for each treatment in ASBOs and then suggest the optimal strategy. After propensity score matching, 128 pairs were included (the NIT and TC groups). The occurrence of severe adverse events (SAEs), peri-treatment clinical parameters, and radiological features were compared between the successful and failed treatment groups. According to different stages of the entire treatment, the independent risk factors for adverse effects for ASBO were analysed in phase I and phase II. In phase I, normal red blood cells (RBC) levels (p = 0.011) and a balanced sodium ion level (p = 0.016) positively affected the outcomes of TC treatment. In phase II, for the TC group, the successful treatment rate reached 79.5% for patients with ASBOs whose normal RBC levels (p = 0.006) or decreasing white blood cells (WBC) levels (p = 0.014) after treatment. For the NIT group, the treatment success rate was 68.1% for patients whose electrolyte imbalance could be reversed or whose neutrophil count/lymphocyte ratio (NLR) levels was lower than 4.3 (p = 0.018). TC treatment is highly recommended for patients with normal RBC counts and sodium levels pretreatment. After dynamic monitoring of the treatment process, for both the TC and NIT groups, once ASBOs had elevated inflammatory biomarkers or irreversible electrolyte disturbances, surgical interference was preferred.
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Obstrucción Intestinal , Intestino Delgado , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Obstrucción Intestinal/terapia , Femenino , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Anciano , Resultado del Tratamiento , Adherencias Tisulares/etiología , Intubación Gastrointestinal/métodos , Adulto , Puntaje de Propensión , Descompresión Quirúrgica/métodos , Factores de RiesgoRESUMEN
There is an urgent requirement to acquire a comprehensive comprehension of novel therapeutic targets for prostate cancer to facilitate the development of medications with innovative mechanisms. In this study, we identified gambogic acid (GBA) as a specific pyroptosis inducer in prostatic cancer cells. By using a thermal proteome profiling (TPP) strategy, we revealed that GBA induces pyroptosis by directly targeting the canopy FGF signaling regulator (CNPY3), which was previously considered "undruggable". Moreover, through the utilization of the APEX2-based proximity labeling method, we found that GBA recruited delactatease SIRT1, resulting in the elimination of lysine lactylation (Kla) on CNPY3. Of note, SIRT1-mediated delactylation influenced the cellular localization of CNPY3 to promote lysosome rupture for triggering pyroptosis. Taken together, our study identified CNPY3 as a distinctive cellular target for pyroptosis induction and its potential application in prostate cancer therapy.
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Neoplasias de la Próstata , Proteoma , Piroptosis , Xantonas , Masculino , Humanos , Xantonas/farmacología , Xantonas/química , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Piroptosis/efectos de los fármacos , Proteoma/metabolismo , Proteoma/efectos de los fármacos , Línea Celular Tumoral , Sirtuina 1/metabolismoRESUMEN
An unprescribed nortriterpenoid with an aromatic E ring, uncanortriterpenoid A (1), together with fourteen known triterpenoids (2-15), were isolated from the hook-bearing stems of Uncaria rhynchophylla Miq. Based on extensive spectroscopic analyses, the NMR data of 2, 5, and 10 in CD3OD were assigned for the first time, and the wrongly assigned δC of C-27 and C-29 of 2 were revised. Among the known compounds, 7, 13, and 15 were isolated from this species for the first time, and 15 represents the first lanostane triterpenoid bearing an extra methylidene at C-24 for the Rubiaceae family. Additionally, compounds 6 and 14 exhibited moderate ferroptosis inhibitory activity, with an EC50 value of 14.74 ± 0.20 µM for 6 and 23.11 ± 1.31 µM for 14.
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Tallos de la Planta , Triterpenos , Uncaria , Uncaria/química , Triterpenos/química , Triterpenos/farmacología , Triterpenos/aislamiento & purificación , Tallos de la Planta/química , Estructura Molecular , HumanosRESUMEN
Objective: This study aimed to investigate the prenatal ultrasonographic diagnosis and prognosis of fetuses with isolated filar cysts (FCs). Methods: The ultrasonographic features, reasons for missed diagnosis, and prognosis of eight isolated FCs diagnosed using ultrasound were analyzed retrospectively through follow-up. Results: Eight isolated FCs showed round or fusiform cystic anechoic areas at the end of the conus medullaris. Among them, six cases were prenatally diagnosed and the other two cases were diagnosed after birth. Of the six cases diagnosed prenatally, four (66.7%) disappeared during pregnancy, and the shortest time to disappearance was 1 month after the first diagnosis. All patients were followed up without any clinical symptoms or functional abnormalities. Conclusion: Isolated FCs may exhibit physiological variations that disappear spontaneously during pregnancy and usually have no clinical symptoms. They are usually benign and have a good prognosis. Ultrasonography is helpful for the diagnosis and follow-up of FCs.
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Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has emerged as an efficient strategy to improve the therapeutic outcomes of immunotherapy. However, the "constantly active" mode of current STING agonist delivery strategies typically leads to off-target toxicity and hyperimmunity. To address this critical issue, herein a metal-organic frameworks-based nanoagonist (DZ@A7) featuring tumor-specific and near-infrared (NIR) light-enhanced decomposition is constructed for precisely localized STING activation and photodynamic-metalloimmunotherapy. The engineered nanoagonist enabled the generation of mitochondria-targeted reactive oxygen species under NIR irradiation to specifically release mitochondrial DNA (mtDNA) and inhibit the repair of nuclear DNA via hypoxia-responsive drugs. Oxidized tumor mtDNA serves as an endogenous danger-associated molecular pattern that activates the cGAS-STING pathway. Concurrently, NIR-accelerated zinc ions overloading in cancer cells further enhance the cGAS enzymatic activity through metalloimmune effects. By combining the synergistically enhanced activation of the cGAS-STING pathway triggered by NIR irradiation, the engineered nanoagonist facilitated the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes for primary tumor eradication, which also established a long-term anti-tumor immunity to suppress tumor metastasis. Therefore, the developed nanoagonist enabled NIR-triggered, agonist-free, and tandem-amplified activation of the cGAS-STING pathway, thereby offering a distinct paradigm for photodynamic-metalloimmunotherapy.
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Inmunoterapia , Rayos Infrarrojos , Proteínas de la Membrana , Estructuras Metalorgánicas , Nucleotidiltransferasas , Fotoquimioterapia , Fotoquimioterapia/métodos , Animales , Proteínas de la Membrana/metabolismo , Nucleotidiltransferasas/metabolismo , Ratones , Humanos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , ADN Mitocondrial/metabolismo , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Nanopartículas/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
The hypothalamus plays a fundamental role in controlling lipid metabolism through neuroendocrine signals. However, there are currently no available drug targets in the hypothalamus that can effectively improve human lipid metabolism. In this study, we found that the antimalarial drug artemether (ART) significantly improved lipid metabolism by specifically inhibiting microglial activation in the hypothalamus of high-fat diet-induced mice. Mechanically, ART protects the thyrotropin-releasing hormone (TRH) neurons surrounding microglial cells from inflammatory damage and promotes the release of TRH into the peripheral circulation. As a result, TRH stimulates the synthesis of thyroid hormone (TH), leading to a significant improvement in hepatic lipid disorders. Subsequently, we employed a biotin-labeled ART chemical probe to identify the direct cellular target in microglial cells as protein kinase Cδ (PKCδ). Importantly, ART directly targeted PKCδ to inhibit its palmitoylation modification by blocking the binding of zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5), which resulted in the inhibition of downstream neuroinflammation signaling. In vivo, hypothalamic microglia-specific PKCδ knockdown markedly impaired ART-dependent neuroendocrine regulation and lipid metabolism improvement in mice. Furthermore, single-cell transcriptomics analysis in human brain tissues revealed that the level of PKCδ in microglia positively correlated with individuals who had hyperlipemia, thereby highlighting a clinical translational value. Collectively, these data suggest that the palmitoylation of microglial PKCδ in the hypothalamus plays a role in modulating peripheral lipid metabolism through hypothalamus-liver communication, and provides a promising therapeutic target for fatty liver diseases.
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Lipoilación , Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Ratones , Microglía , Hipotálamo , Metabolismo de los Lípidos , ArteméterRESUMEN
OBJECTIVES: Colitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered. METHODS: The anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo. RESULTS: AB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice. CONCLUSION: We identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.