Wanfu Bai

Introduction: Liver fibrosis, a severe chronic liver injury sequela, lacks effective therapies. Quercetin, a natural flavonoid, exhibits multi-target anti-fibrotic potential. Methods: This study integrated network pharmacology,metabolomics, molecular docking, and molecular dynamics simulations to investigate its mechanisms. Results: Network analysis identified 203 overlapping targets, with core targets including protein kinase B (AKT1), interleukin-6 (IL6), tumor protein p53 (TP53), and tumor necrosis factor (TNF), which were enriched in PI3K-Akt and TNF signaling pathways. In CCl4- induced rats (quercetin 50 mg/kg/day), quercetin alleviated pathological damage, significantly reduced collagen area by 43.1% (P = 0.006), and lowered serum alanine aminotransferase, aspartate aminotransferase, and type III procollagen levels. Metabolomics revealed 32 differential metabolites, implicating multiple metabolic pathways including lipid and amino acid metabolism. Molecular docking showed strong binding to AKT1 (5.8 kcal/mol) and TNF (7.2 kcal/ mol), with stable complexes over 100 ns simulations. QPCR was used to detect the expression of PI3K/AKT1 core targets in liver tissue, and experimental verification confirmed the predicted key targets. Conclusion: This multi-faceted study elucidates quercetin’s anti-fibrotic mechanism, laying a foundation for its therapeutic development.

Hepatic fibrosis is a common chronic liver disease, and its pathogenesis and influencing factors exhibit diverse characteristics. Pharmacological intervention is currently the main therapeutic approach for hepatic fibrosis. Quercetin is a flavonoid compound with multiple biological activities, which can inhibit inflammatory responses, reduce oxidative stress, suppress hepatic stellate cell activation and excessive collagen deposition, and regulate hepatic lipid metabolism, thus exerting anti-hepatic fibrosis effects. Quercetin delays the progression of fibrosis via regulating signaling pathways such as Rac1/NOX1 and transforming growth factor-β1/Smad, thereby diminishing the activity of hepatic stellate cells and their accumulation in the extracellular matrix. Quercetin can also enhance the activity of antioxidant enzymes (such as superoxide dismutase and glutathione peroxidase) and reduce the damage of oxidative free radicals to hepatocytes by regulating the nuclear factor E2-related factor 2/antioxidant response element signaling pathway. Furthermore, it can inhibit the activation of the Toll-like receptor 4/nuclear factor-κB pathway and reduce the expression of pro-inflammatory factors, thus alleviating the inflammatory response. Concurrently, quercetin plays an active role in terms of regulating liver lipid metabolism, reducing abnormal lipid accumulation, and lessening the burden on hepatocytes. The multi-target and multi-pathway functional properties of quercetin render it highly promising in alleviating the pathological progression of liver fibrosis. This article summarizes the signaling pathways and target roles of quercetin in the treatment of liver fibrosis, providing an important reference for clinical intervention strategies and novel drug research and development.

Background: Age, biomarkers including pepsinogen and gastrin, and Helicobacter pylori (H pylori ) might be risk factors in nodular gastritis (NG), however, the detailed relationship between the risk factors and inflammation in NG remains explored. Thus, we aimed to determine the association of age, pepsinogen and gastrin levels and NG patients infected by H pylori . Methods: A total of 768 cases of NG patients were identified in the endoscopic procedure records spanning from 2019 to 2023 at the Baotou Medical College, who were divided into 7 age-based groups: 8 to 17, 17 to 30, 31 to 40, 41 to 50, 51 to 60, 61 to 70, and 71 to 80 years. Results pertaining to serum gastric function test, endoscopic findings, histological examinations, and C13 urea breath tests were systematically compiled from the patients’ medical records. Results: The prevalence of 768 NG patients exhibited a “parabolic pattern” with increasing age. Peaks were observed 41 to 50 group, especially in female patients. Among these patients, 73.6% were female patients. Besides, there was a significant difference in pepsinogen I (PGI)/pepsinogen II (PGII) ratio between the mild infection and the others group. Additionally, a similar significant difference was observed between the moderate infection group and the other groups. The logistic multiple regression analysis facilitated the combined assessment of various biomarkers such as PGI, PGII, PGI/PGII, and gastrin-17 (G-17), resulting in a sensitivity of 73.7% and a specificity of 97.9%. Conclusions: NG patients demonstrated a parabolic distribution pattern based on age. And, the elevated levels of PGI, PGII and G-17 observed in patients could signify their contributory role in the initiation and progression of NG.

Hepatic fibrosis (HF), a reversible yet critical pathological stage in chronic liver disease progression, represents a major global public health challenge. This study systematically investigated the antifibrotic mechanism of Prunus mongolica oil (OIL), an active component derived from traditional medicinal plants, through an integrated approach combining pharmacodynamics, transcriptomics, and molecular biology in carbon tetrachloride (CCl₄)-induced Sprague–Dawley rat models. Dose–response evaluation revealed optimal antifibrotic efficacy at the medium dosage (5 g kg⁻¹) compared with other concentrations (2.5 and 7.5 g kg⁻¹). Transcriptomic profiling identified 1734 differentially expressed mRNAs, 121 lncRNAs, and 82 miRNAs among model (MOD), control (CON), and OIL-treated groups. Construction of competing endogenous RNA (ceRNA) networks and functional enrichment analysis highlighted the potential association of the PPAR signaling pathway (P = 0.012, FDR = 0.27). Topological assessment using Cytoscape (v3.9.1) and the STRING database identified the Gck/rno-miR-667-5p/Cyp8b1 axis as the central regulatory node. Mechanistically, OIL exerted dual therapeutic effects: (1) upregulating PGC-1α/PPARγ expression to enhance metabolic reprogramming, and (2) suppressing TGF-β/Smad3 phosphorylation activation, thereby inhibiting hepatic stellate cell (HSC) activation and extracellular matrix (ECM) deposition. Immunohistochemical and western blot analyses validated these protein-level modulations. Our findings revealed a novel ceRNA-network-mediated mechanism wherein OIL attenuates hepatic fibrosis through coordinated regulation of PPAR and TGF-β/Smad3 pathways via the Gck/rno-miR-667-5p/Cyp8b1 axis, providing a theoretical foundation for developing multitarget phytopharmaceuticals against liver fibrosis.

Introduction: Hepatic Fibrosis (HF), a pathological remodeling process triggered by persistent liver damage, is marked by the excessive buildup of extracellular matrix (ECM), leading to a gradual deterioration of liver function and an increased likelihood of advancing to cirrhosis and liver failure.Methods: This study adopts a systematic pharmacology methodology, initially employing bibliometric analysis to identify traditional Chinese medicine (TCM) formulations and individual herbs with potential anti-HF properties. Subsequently, a multi-dimensional network analysis is conducted to pinpoint core active components. Experimental investigations involve the construction of a carbon tetrachloride (CCl₄)-induced rat model of liver fibrosis, complemented by transcriptomic technology to systematically elucidate the mechanisms of action of the active components in TCM.Results: In this study, kaempferol (KA), identified as the principal active compound with anti-fibrotic properties, was selected from traditional Chinese medicine (TCM) and TCM prescriptions through a combination of bibliometric analysis and network pharmacology. Pharmacodynamic evaluations, including pathological section analyses, demonstrated that KA effectively mitigated the fibrotic process and decreased collagen deposition. Further corroborated by ELISA experiments, kaempferol exhibited pronounced anti-fibrotic effects, inhibited inflammatory responses, restored liver function indices, and ameliorated the progression of liver fibrosis. Mechanistic investigations revealed that KA modulated fatty acid metabolism, retinol metabolism, and arachidonic acid metabolism by regulating the expression of key metabolic enzyme genes such as SCD, SCD2, FADS2, and CYP4A8, and significantly influenced the activity of the PPAR signaling pathway. Additionally, it impacted the dysregulation of lipid metabolism and inflammatory response pathways, significantly inhibited hepatic stellate cell (HSC) activation, and reduced ECM accumulation.Discussion: This finding elucidates the mechanism by which KA attenuates HF through multi-target regulation, and provides a theoretical basis for metabolic reprogramming-based therapeutic strategies with translational valu.

Pulmonary fibrosis (PF) is a challenging and intricate lung ailment to treat. Saorilao-4 decoction (SRL) is a traditional Mongolian medicine remedy frequently utilized in the management of lung disorders. This study employed transcriptomics and metabolomics to explore the molecular mechanisms of SRL in the bleomycin-induced PF rat model. Additionally, histopathological analysis and the assessment of serum biochemical indices were utilized to investigate the potential mitigating effects of SRL on PF. Transcriptomics and metabolomics analyses indicate that SRL primarily modulates the adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptors (PPAR) signaling pathways by regulating genes such as Scd, Fads2, Cpt1a, Lipe, Pfkfb3, and Hmgcs2. Thereby influencing biomarkers such as S-Adenosylmethioninamine (SAM), 16-hydroxyhexadecanoic acid, and proline, mitigating metabolic disorders in pathways such as arginine and proline metabolism, vitamin B6 metabolism, fatty acid degradation, and arachidonic acid metabolism. The present study reveals the regulation of unsaturated fatty acid-related metabolic pathways in vivo and elucidates the mechanism of action of SRL in ameliorating PF.

Pulmonary fibrosis (PF) is a chronic progressive disease marked by alveolar epithelial cell damage. Saorilao‐4 decoction (SRL), a traditional Mongolian prescription, has demonstrated therapeutic effects on PF, though its mechanism of action remains elusive. This study used a bleomycin‐induced fibrosis rat model to evaluate SRL's effects by measuring inflammatory factors, assessing fibrosis‐related indices, and performing histopathological lung examinations. Serum metabolite levels in the experimental groups were measured using high‐performance liquid chromatography coupled with mass spectrometry. Data analysis involved principal component and partial least‐squares discriminant analyses, followed by functional enrichment analysis of differential metabolites. SRL significantly ameliorated alveolar interstitial injury, fibrosis, and metabolic disorders induced by bleomycin. Additionally, we identified 71 metabolic components related to PF progression, including sphingolipids and fatty acids. Administration of SRL affected 59 metabolic components involved in purine, cysteine and methionine, and arginine and proline metabolisms. Specifically, SRL regulated the levels of hexadecanoic acid, S‐adenosylmethionine, 3‐oxopalmitoyl coenzyme A, and dodecanoic acid metabolites, thereby improving the metabolic course of PF. In conclusion, this study offers insights into the potential mechanisms of SRL in treating PF from a metabolomics perspective. It provides valuable information for its clinical application.

Pulmonary fibrosis (PF) is a progressive and incurable lung disease for which treatment options are limited. Here, we aimed to conduct an exploratory study on the effects of the Mongolian medicine Saorilao-4 (SRL) on the gut microbiota structure, species abundance, and diversity of a rat PF model as well as the mechanisms underlying such effects. Rat fecal samples were analyzed using 16S rRNA sequencing technology. Bioinformatic and correlation analyses were performed on microbiota data to determine significant associations. SRL substantially attenuated the adverse effects exerted by PF on the structure and diversity of gut microbiota while regulating its alpha and beta diversities. Linear discriminant analysis effect size enabled the identification of 62 differentially abundant microbial taxa. Gut microbiota abundance analysis revealed that SRL significantly increased the relative abundance of bacterial phyla such as Firmicutes and Bacteroidetes. Moreover, SRL increased the proportion of beneficial bacteria, such as Lactobacillus and Bifidobacteriales, decreased the proportion of pathogenic bacteria, such as Rikenellaceae, and balanced the gut microbiota by regulating metabolic pathways. SRL may attenuate PF by regulating gut microbiota. This exploratory study establishes the groundwork for investigating the metagenomics of PF.

The main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1β, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.