Search Results (1,942)

Background/Objectives: Baicalin (BA), a natural flavonoid with anti-inflammatory activity, shows promise for treating acute pharyngitis (AP) but its clinical application is hindered by poor water solubility and low oral bioavailability. Based on the clinically validated traditional Chinese medicine formula Pudilan Oral Liquid, we identified that BA and chlorogenic acid (CGA) can self-assemble into nanocomplexes (BA-CGA@NPs). This study aims to construct such a nanocomplex to enhance BA absorption and anti-AP efficacy with favorable biocompatibility. Methods: BA-CGA@NPs were prepared via supramolecular self-assembly and characterized by dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and molecular dynamics simulation (MDS). In vivo pharmacokinetics evaluated BA absorption. Biocompatibility and therapeutic efficacy were assessed using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and an AP rat model. Results: BA-CGA@NPs were successfully formed with enhanced biocompatibility. In vitro, they reduced nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) in macrophages. In AP rats, oral BA-CGA@NPs significantly increased systemic BA exposure, ameliorated pharyngeal histopathology, and lowered IL-1β, TNF-α, and interleukin-6 (IL-6) in serum and pharyngeal tissue, outperforming free BA or CGA alone. Mechanistic studies suggested that the anti-inflammatory effect was associated with modulation of the Toll-like receptor 4 (TLR4)/MyD88/Nuclear factor-κB (NF-κB) signaling pathway. Conclusions: Self-assembled BA-CGA@NPs enhance BA absorption and biocompatibility, alleviating AP inflammation through mechanisms associated with modulation of the TLR4/MyD88/NF-κB pathway, offering a promising nano-traditional Chinese medicine strategy for poorly soluble active ingredients. Full article

Low-density granulocytes (LDGs) have been implicated in the pathogenesis of several autoimmune diseases, yet their role in Sjögren’s disease (SjD) remains poorly understood. We enrolled 90 SjD patients and 30 healthy controls (HCs) and identified LDGs as CD14^−/lowCD15⁺ cells by flow cytometry, with intracellular interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) staining, and further analyzed CD16 as a maturation marker in LDGs and T helper 17 (Th17) cell frequency. LDG percentages were significantly elevated in active SjD compared with inactive patients (p < 0.001) and HCs (p < 0.0001), and correlated positively with EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) (r = 0.355, p = 0.0006), erythrocyte sedimentation rate (ESR) (r = 0.325, p = 0.0061), γ-globulin (r = 0.334, p = 0.0177), and Th17 frequency (r = 0.537, p = 0.0068). LDG expansion was accompanied by enrichment of immature CD16^−/low cells (r = −0.798, p = 0.0100). Patients with renal or pulmonary involvement showed higher LDG levels (p = 0.0004), and in SjD -associated interstitial lung disease (SjD-ILD) patients, LDG percentage showed a positive but non-significant trend with serum Krebs von den Lungen-6 (KL-6) levels (r = 0.497, p = 0.102). LDG levels decreased following treatment in longitudinally followed patients, and LDGs from active patients exhibited higher IL-6 and TNF-α production ratios relative to monocytes than those from inactive patients. Stratification by LDG levels revealed significant associations with disease activity, laboratory parameters, and organ involvement. These findings suggest that LDGs are associated with disease activity and organ involvement, may serve as potential biomarkers, and may contribute to the pathogenesis of SjD. Full article

Background/Objectives: Glycation, a non-enzymatic post-translational modification, can increase structural heterogeneity in therapeutic monoclonal antibodies (mAbs) and is considered a critical quality attribute in biosimilar (BS) development. Despite extensive studies on glycation in individual mAbs, comparative reports on originator (OR) and BS mAbs under forced glycation conditions remain limited. This study aimed to comparatively evaluate the glycation profiles of one OR and three BS anti-tumor necrosis factor-alpha (anti TNF-α) mAb products using integrated mass spectrometry-based methods. Methods: Forced glycation was induced by incubating mAbs with 200 mM D-glucose at 37 °C for 7 days. Intact mass analysis and peptide mapping were used to assess glycation extent and site distribution, respectively. Results: Intact mass analysis revealed a consistent mass increase of approximately 486 Da across all major glycoform species for each mAb product, indicating predominant formation of the tri-glycated mAb population under the applied stress conditions. The overall glycation levels were comparable at the intact level, ranging from 67% to 73% among the OR and BS mAb products. Peptide mapping identified nine glycated lysine (K)-containing peptides, among which three major glycation hotspots (LC:V5 K145/K149, LC:V7 K183, and HC:V7 K250/K252) showed elevated occupancies (~10–16%). These sites collectively accounted for the dominant intact level mass shift. The remaining glycated peptides exhibited only minimal modification levels (<2%). Despite their distinct manufacturing processes, all tested mAb products showed nearly identical site-specific glycation profiles. Conclusions: Forced glycation susceptibility in the studied mAbs was driven by a limited set of structurally preferred K hotspots, leading to highly comparable glycation profiles across OR and BS mAb products. The combined intact mass and peptide mapping strategy provides a robust analytical platform for comparative glycation assessment in BS characterization. Full article

Sickness is a universal human problem. A significant proportion of the world’s population suffers from one disease or another, while some individuals have two or more chronic diseases simultaneously. The development of one disease, if not properly managed, can often lead to other coexisting health challenges, a condition known as comorbidity. Unfortunately, treating comorbidity is difficult due to overlapping symptoms and the risk of drug interactions. To overcome these challenges, it is necessary to identify active principles with broad-spectrum therapeutic properties. Therefore, this study provides an overview of the multifunctional role of lactoferrin against various human diseases. Information regarding the role of lactoferrin in combating various human diseases was gathered through a systematic literature search. Findings from a retrospective pilot study indicated that lactoferrin has the potential to alleviate symptoms of interstitial cystitis, or painful bladder syndrome. Additionally, lactoferrin has anti-inflammatory, anti-diabetic, anti-cancer, anti-obesity, and antimicrobial properties. It could be beneficial in addressing issues related to microbial drug resistance. The anti-inflammatory effects of lactoferrin are linked to the reduction in cytokines such as tumor necrosis factor-alpha (TNF-α), IL-6, and IL-1β; inhibition of Inhibitory kappa B kinase beta (IKK-β) activity; and suppression of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, lactoferrin may provide protection against liver, kidney, and cardiac injuries. Lactoferrin’s wide-ranging benefits indicate that it may be used in conjunction with current medications to help treat multiple health issues simultaneously. Full article

Gastric cancer is among the leading causes of cancer-related deaths worldwide. Modern treatment approaches include nanoparticles (NPs) designed to target cancer cells, which release a therapeutic cargo facilitating the inhibition of their expansion, thereby improving anti-tumor therapies. The success of NPs, created to deliver anticancer agents and biologically active compounds, may depend on selecting the way to target cancer cells. This study focused on examining the effects of NPs made of polylactic acid (PLA) with histamine (His) end groups and loaded with 5-fluorouracil (5-FU), a known anticancer drug (PLA-His-5-FU), on human gastric cancer AGS cells in vitro. The incubation of AGS cells with PLA-His-FU NPs resulted in diminished mitochondrial membrane potential and the induction of cell apoptosis, along with cell cycle arrest and the reduction of cell proliferation. Furthermore, the NPs tested provoked the secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β by AGS cells and induced the activation of the nuclear factor kappa B (NF-κB) signaling pathway in THP-1 blue monocytes, which indicates the ability to promote the development of a milieu for the infiltration and activation of immunocompetent cells. NPs did not increase intracellular adhesion molecule (ICAM-1) deposition on AGS cells, thus potentially preventing the distribution of cancer cells. In conclusion, PLA-His-5-FU NPs show promising anticancer activity for gastric cancer AGS cells in vitro, better than PLA-OH-5-FU, and can be used in further in vivo studies to confirm this activity. Full article

Objective: The purpose of this study is to study cytokine indicators for the identification of severe fever with thrombocytopenia syndrome (SFTS) severity. Methods: We searched the literature in PubMed, Embase, and Web of Science published before 7 April 2026. The main results are presented as forest plots. Subgroup analyses, sensitivity analyses, and publication bias were also performed. Results: A total of 22 articles were eventually included in our study. Our findings demonstrate that circulating concentrations of Interleukin-6 (IL-6) (SMD = 2.02, 95% CI: 1.53–2.51, I² = 95.2%), Interleukin-10 (IL-10) (SMD = 1.18, 95% CI: 0.92–1.44, I² = 71.3%), Interleukin-8 (IL-8) (SMD = 0.91, 95% CI: 0.61–1.20, I² = 69%), Tumor necrosis factor-alpha (TNF-α) (SMD = 0.70, 95% CI: 0.43–0.96, I² = 64.6%), Interferon-gamma (IFN-γ) (SMD = 1.32, 95% CI: 0.69–1.95, I² = 89.1%), Interleukin-1 beta (IL-1β) (SMD = 1.78, 95% CI: 0.85–2.71, I² = 94.8%), Monocyte chemoattractant protein-1 (MCP-1) (SMD = 1.15, 95% CI: 0.80–1.50, I² = 46.1%), Interferon-alpha (IFN-α) (SMD = 1.53, 95% CI: 0.38–2.68, I² = 89.6%), Granulocyte Colony-Stimulating Factor (G-CSF) (SMD = 1.79, 95% CI: 0.99–2.59, I² = 68.1%) and Inducible protein 10 (IP-10) (SMD = 1.11, 95% CI: 0.60–1.62, I² = 58.3%) are significantly elevated in patients with severe SFTS compared with those with mild disease, whereas Transforming Growth Factor-beta (TGF-β) (SMD = −0.51, 95% CI: −0.78–−0.24, I² = 6.0%) and RANTES (SMD = −0.10, 95% CI: −0.40–0.20, I² = 0.0%) levels are reduced in the severe group. Conclusions: By analyzing the cytokine indicators of SFTS patients, we have found some indicators that are representative of SFTS severity. Our findings provide a clinically actionable basis for early severity prediction and further useful evidence for clinicians to manage severe patients efficiently. Full article

Older adults and individuals with chronic obstructive pulmonary disease (COPD) are vulnerable to the harmful health effects of fine particulate matter (PM_2.5), which are partly driven by systemic inflammation. This study examined whether older adults with COPD exhibit greater inflammatory responses to PM_2.5 than age-matched healthy controls. We compared circulating high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha in 38 patients with COPD (73.6 ± 7.1 years) and 20 controls (70.9 ± 5.2 years) during high- and low-pollution periods. In the COPD group, 65.8% used inhaled corticosteroids and 42.1% used statins; 65.0% of controls used statins. Mean PM_2.5 concentrations were higher in the high-pollution period than the low-pollution period (79.1 ± 23.3 vs 13.9 ± 3.6 µg/m³; p < 0.001). Across both periods, IL-8 was higher in COPD than in controls, without significant within-group increases during high pollution. These findings indicate higher baseline systemic inflammation in COPD, while pollution-associated increases may be attenuated by anti-inflammatory medications. However, this should be interpreted cautiously given the observational design. Full article

Although perioperative oxygen therapy is a routine component of general anesthesia, its early biological consequences remain incompletely understood. This prospective randomized study evaluated whether perioperative oxygen concentration influences early biomarker responses in adults undergoing elective laparoscopic lower abdominal surgery. Patients received either normoxia (FiO₂ 0.35) or hyperoxia (FiO₂ 0.80) under standardized anesthesia. Clear physiological separation between groups was confirmed by arterial blood gas analysis. The primary biomarker finding was that circulating surfactant protein-A (SP-A) increased significantly in the normoxia group, whereas no comparable increase was observed under hyperoxia. Syndecan-1 and sialic acid showed descriptively similar directional patterns; however, these secondary biomarker findings were interpreted as exploratory and were not robust after Holm correction. By contrast, tumor necrosis factor-alpha (TNF-α) levels were higher postoperatively in the hyperoxia group, while ischemia-modified albumin (IMA) and total protein did not differ significantly between groups. These findings suggest that perioperative hyperoxia was associated with different early circulating biomarker trajectories across pulmonary epithelial and glycocalyx-related domains, without establishing pulmonary or endothelial protection. Further studies are needed to determine whether these early mechanistic findings translate into clinically meaningful outcomes. Full article

Background/Objectives: Severe mitral regurgitation (MR) is associated with chronic atrial stretch, chamber enlargement, pulmonary pressure elevation, and atrial fibrosis, yet the relationship between tissue inflammatory/profibrotic signaling, histologically quantified fibrosis, and echocardiographic remodeling remains incompletely characterized. This study aimed to compare biatrial tissue remodeling in patients with severe MR undergoing mitral valve surgery with a practical non-valvular surgical comparator group undergoing isolated coronary artery bypass grafting (CABG). Methods: This single-center, observational, cross-sectional comparative study included 36 elective cardiac-surgery patients: 22 with severe MR and 14 undergoing isolated CABG without significant valvular disease. Left- and right-atrial tissue samples were collected intraoperatively. IL-6, TNF-α, and TGF-β expression was assessed by quantitative real-time PCR using pooled atrial samples stratified by atrial side and study group, whereas atrial fibrosis was quantified histologically on individual tissue specimens using Masson’s trichrome staining and digital image analysis. Clinical, laboratory, and echocardiographic parameters were compared between groups, and exploratory associations were assessed with cautious interpretation. Results: Compared with the CABG comparator group, patients with severe MR showed a pooled molecular profile compatible with higher aggregate atrial expression of IL-6, TNF-α, and TGF-β; because qPCR was performed on pooled tissue preparations, these molecular findings were interpreted descriptively and were not used for patient-level inferential statistics. Histologically quantified fibrosis was significantly increased in severe MR in both the left atrium (29.69 ± 12.26% vs. 12.17 ± 4.56%, p < 0.0001) and the right atrium (25.25 ± 11.33% vs. 9.01 ± 4.46%, p < 0.0001). The MR group also showed more pronounced echocardiographic remodeling, including larger estimated left atrial volume, higher pulmonary artery systolic pressure, and greater right ventricular diameter. Exploratory individual-level analyses were restricted to histological fibrosis and echocardiographic variables. Conclusions: Severe MR was associated with marked echocardiographic remodeling and significantly greater histologically quantified biatrial fibrosis compared with a CABG surgical comparator group. Pooled qPCR findings support an aggregate inflammatory/profibrotic signal, but they should be interpreted descriptively because individual-level molecular variability could not be assessed. These findings are hypothesis-generating and do not establish causality. Full article

Exercise generally elicits changes in bone and inflammatory biomarkers, but it is unclear if these changes are related. The purpose of this secondary analysis was to investigate associations between bone and inflammatory biomarkers before and after a single bout of high-intensity/impact exercise and post-exercise nutrition. In a repeated measures crossover design, 13 healthy, young adult females (age = 20.3 ± 2.3 y) performed high-intensity resistance and impact exercise followed by nutrient consumption (skim milk and an isoenergetic carbohydrate beverage). Venous blood was obtained pre-exercise, 15 min, 75 min, 24 h, and 48 h post-exercise. Serum bone biomarkers (cross-linked C-telopeptide of type I collagen [CTX], receptor activator of NF-κB ligand [RANKL], sclerostin [SOST], osteoprotegerin [OPG], total osteocalcin [OC]) and cytokines (interleukin [IL]-1β, IL-6, IL-10, and tumor necrosis factor-alpha [TNF-α]) were measured. Separate linear mixed regression models were performed for each bone biomarker. There were significant associations between bone and inflammatory biomarkers, including CTX with TNF-α (positive) and IL-10 (negative), OPG with TNF-α (negative) and IL-10 (positive), RANKL with IL-6 (positive) and SOST with TNF-α (negative) and IL-10 (positive). Thus, relationships exist between inflammatory and bone biomarkers in the context of an exercise and nutrition stimulus, which may have implications for optimizing exercise recovery strategies. Full article

Macrophage polarization toward the pro-inflammatory M1 phenotype underlies an effective strategy for potentiating antitumor immune responses. Electrical stimulation has emerged as a potent modulator of immune cell polarization. However, conventional electrode-mediated electrical stimulation has limited penetration into deep tissues and relies on external power supplies. Here, we report on ultrasound (US)-responsive piezoelectric nanofibers, constructed by embedding manganese–titanium metal–organic frameworks (MT-MOF) within a polyacrylonitrile (PAN) matrix (MT-MOF/PAN). As a non-centrosymmetric bimetallic framework, MT-MOF generates a heterogeneous charge distribution under mechanical deformation, thereby enhancing the composite’s piezoelectric output. Furthermore, interfacial coupling between MT-MOF and the PAN nanofibers provides an additional contribution to this enhancement. Under US stimulation, MT-MOF/PAN nanofibers generates a peak voltage of 0.24 V, substantially exceeding the output of pure PAN nanofibers. In RAW-Blue cells, US-activated MT-MOF/PAN nanofibers significantly activate the nuclear factor-κB (NF-κB) pathway and promote the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), whereas neither US nor nanofibers alone produce this effect. Mechanistic studies demonstrate that piezoelectric stimulation induces a transient intracellular Ca²⁺ influx, as visualized by Fluo-4 acetoxymethyl ester (Fluo-4 AM) imaging, whereas US alone or nanofibers alone produce no significant effects. These findings establish MT-MOF/PAN nanofibers as a wireless, electrode-free platform for antitumor immunotherapy. Full article

Neutrophils are essential for antimicrobial defense through reactive oxygen species (ROS) production, tumor necrosis factor-alpha (TNF-α) release, and neutrophil extracellular trap formation. Lipoic acid, a redox-active antioxidant, modulates activation in human neutrophils. Neutrophils isolated from healthy donors were pretreated with lipoic acid and then exposed to lipopolysaccharide (LPS) or whole Escherichia coli, according to the specific assay. ROS production, NET formation, TNF-α release, bacterial killing, metabolic activity, and cell death were assessed using fluorometric assays, enzyme-linked immunosorbent assay, colony-forming unit assays, MTT reduction, and Annexin V-FITC/propidium iodide flow cytometry. Lipoic acid significantly reduced ROS production and NET formation induced by LPS and Escherichia coli. at 0.5 mM, lipoic acid also reduced E. coli-induced NET formation by approximately 50% and attenuated TNF-α release at early stimulation times. In colony-forming unit assays, lipoic acid did not significantly reduce neutrophil-mediated killing of Escherichia coli or Staphylococcus aureus. Although only neutrophil preparations with high baseline viability were used, Escherichia coli challenge markedly reduced cell viability during the assay; under this condition, lipoic acid pretreatment limited bacteria-induced necrosis and preserved a higher proportion of viable neutrophils. These findings indicate that lipoic acid dampens excessive oxidative and inflammatory neutrophil responses while maintaining measurable bactericidal capacity in vitro. Full article

Lipopolysaccharide (LPS) impairs the function of ovine follicular granulosa cells (GCs), representing a primary cause of follicular atresia. Selenium (Se), an essential trace element, possesses anti-inflammatory and cytoprotective properties; however, its effects on GC ultrastructure remain largely unknown. In this study, primary ovine GCs were exposed to LPS (10 µg/mL) and treated with sodium selenite (25 nM). Transmission electron microscopy (TEM), JC-1 staining, enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) detection, flow cytometry, and quantitative real-time PCR (qRT-PCR) were employed to evaluate cellular ultrastructure, mitochondrial membrane potential (ΔΨm), and downstream physiological processes. LPS induced severe mitochondrial pyknosis, cristae loss, and reduced ΔΨm, accompanied by inflammation, oxidative stress, apoptosis, and impaired steroidogenesis. Se intervention markedly ameliorated these ultrastructural injuries, preserving mitochondrial morphology and ΔΨm. Functionally, Se suppressed the release of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β); enhanced the activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) while attenuating ROS accumulation; inhibited apoptosis by upregulating BCL-2 and downregulating BAX and CASPASE-3; and restored E₂ and P₄ secretion via upregulation of STAR and NR5A1. This study provides direct morphological evidence that Se protects ovine GCs from LPS-induced damage by repairing mitochondrial ultrastructure. This structural restoration is central to its integrated anti-inflammatory, antioxidant, anti-apoptotic, and steroidogenic effects. These in vitro findings suggest that Se may serve as a promising nutritional strategy for mitigating inflammation-driven follicular atresia, pending further in vivo validation. Full article

Metabolic dysfunction-associated steatohepatitis (MASH; formerly non-alcoholic steatohepatitis, NASH) is characterized by oxidative stress, inflammatory activation, hepatocellular injury, and progressive liver dysfunction. However, the global transcriptomic landscape underlying stress-induced hepatic injury remains incompletely understood. In this study, we employed a methionine–choline-deficient (MCD) diet-induced murine model to characterize the phenotypic and transcriptomic alterations associated with liver injury. Male C57BL/6J mice were fed either a control or MCD diet, and hepatotoxicity was assessed by survival analysis, body and liver weight measurements, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, histopathological examination, RNA sequencing, quantitative real-time PCR (qRT-PCR), and tumor necrosis factor-alpha (TNF-α) enzyme-linked immunosorbent assay (ELISA). MCD feeding markedly reduced survival and body weight while inducing hepatomegaly and significant elevations in serum ALT and AST, indicating severe hepatocellular injury. Histopathological analysis demonstrated hepatic steatosis, hepatocellular ballooning, and lobular inflammation without histological evidence of fibrosis. Transcriptomic profiling revealed extensive gene expression remodeling, characterized by activation of inflammatory pathways, enrichment of MAPK-related signaling, dysregulation of lipid metabolism, suppression of antioxidant defense systems, impairment of cytochrome P450-mediated detoxification, and upregulation of apoptosis-associated genes. qRT-PCR further validated the differential expression of representative genes involved in inflammatory signaling (Tlr4, Nfkb1, Nlrp3, and Casp1), MAPK signaling (Fos), xenobiotic metabolism (Cyp4f18), lipid metabolism (Apoa4 and Lpl), extracellular matrix remodeling (Mmp12), and oxidative stress responses (Sod1 and Gstp1). In addition, elevated serum TNF-α levels provided protein-level evidence supporting activation of the TLR4/NF-κB/TNF-α/NLRP3 inflammatory axis. Although fibrosis-associated transcriptional responses were detected, the absence of histological fibrosis suggests transcriptional priming of fibrogenic pathways rather than established fibrogenesis. Collectively, these findings provide a transcriptomic framework linking oxidative stress, impaired detoxification, inflammatory activation, and stress-responsive signaling to MCD-induced hepatic injury. The MCD model provides a valuable experimental platform for characterizing hepatic stress-response transcriptomes and for generating hypotheses that can subsequently be evaluated in environmentally relevant toxicological models. Nevertheless, caution should be exercised when extrapolating these findings to obesity-associated human MASLD, as the MCD model lacks key metabolic features of the human disease, including obesity and insulin resistance. Therefore, the present findings should be interpreted primarily as transcriptomic signatures of stress-induced hepatic injury rather than as a direct representation of the pathophysiological processes underlying human obesity-associated MASLD. Full article

Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG. Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism. Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived from Coptis chinensis Franch. and Pogostemon cablin (Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism. Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota–SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG. Full article