Paederia scandens (Lour.) Merr. (P. scandens), as an edible and medicinal herb, is commonly used for treating gastric ulcer in China; however, its mechanistic and effective substances studies remain limited. This study aimed to investigate the antigastric ulcer effects of aqueous extracts of P. scandens (PS-AE) and explore the involvement of NF-κB signaling in this effect. In addition, the study aimed to identify the effective substances by exploring NF-κB inhibitors. The main components of PS-AE were identified using an UPLC-MS method. HCl/EtOH-induced acute gastric ulcer in rats, and LPS-stimulated RAW264.7 cells were used to determine the antigastric ulcer effects of PS-AE in vivo and in vitro, respectively. Histopathological changes of the ulcer tissues were observed using staining methods of HE and PAS; secretions of inflammatory cytokines and oxidative stress indexes were measured using biochemical test kits; protein levels of NF-κB signaling pathway-related molecules were measured using Western Blot. NF-κB inhibitors identification in P. scandens was performed by developing HipHop pharmacophore model, and the results were further validated by molecular docking. In vivo, PS-AE significantly attenuated gastric ulcer in rats; reduced inflammation by adjusting the inflammatory cytokines TNF-α, IL-1β, and IL-6 levels; and induced oxidative stress can be alleviated via adjusting the levels of SOD, MDA, and GSH-Px. In addition, PS-AE may play an anti-inflammatory role mainly through NF-κB signaling pathway. Following pharmacophore modeling and molecular docking, 13 potential inhibitors targeting NF-κB were identified. In addition, in vitro, PS-AE and paederoside could significantly inhibit the activation of NF-κB p65 and the productions of downstream cytokines including NO, TNF-α, and IL-6. PS-AE protective effects on gastric ulcer damage induced by HCl/EtOH in rats, which is probably associated with its antioxidant effect and the inhibitory effects on levels of inflammatory mediators regulated by NF-κB signaling pathway. 13 potential NF-κB-targeting inhibitors are probably effective substances contributing to the herbs pharmacological effect. In practical application, Paederia scandens, a traditional food and medicinal plant, possessed diversified chemical components and multiple pharmacological activities (anti-inflammatory, bacteriostasis, and antioxidative.). In China, P. scandens has been used as a traditional medicine to treat gastritis for hundreds of years, and it may be a potentially effective dietary product to improve gastric ulcer. This study shows that P. scandens exerts protective effects on gastric ulcer damage induced by HCl/EtOH in rats, which is probably associated with its antioxidant effect and the inhibitory effects on levels of inflammatory mediators regulated by NF-κB signaling pathway, which provides pharmacological justifications for the functional food use of P. scandens for treating gastric disease.

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. A modified traditional Chinese medicine (TCM) formula, “Jiawei Jianpi Huoyu Formula (JJHF)”, has been reported to be effective in relieving UC symptoms, but its potential pharmacological components and targets remain unclear. Methods: This study employs an integrative approach combining network pharmacology, machine learning, molecular docking, Mendelian randomization (MR), and experimental validation to investigate the therapeutic mechanisms of JJHF in UC. Results: We identified 199 intersecting targets that were considered potential JJHF targets for treating UC. Network analysis revealed quercetin, luteolin, and kaempferol as key components modulating inflammatory pathways such as TNF and IL-6. Machine learning identified four core targets associated with UC progression, including glycogen synthase kinase 3 beta (GSK3B), vascular cell adhesion protein 1 (VCAM1), caspase-1 (CASP1), and heat shock protein family A member 5 (HSPA5). Molecular docking confirmed strong binding affinities between these targets and JJHF components, particularly β-sitosterol and HSPA5. In vitro experiments demonstrated that JJHF’s efficacy in reducing LPS-induced inflammatory cytokines (IL-1β, TNF-α, MCP-1) and downregulating the expression of HSPA5, GSK3B, VCAM1, and CASP1 mRNA expression in RAW264.7 macrophages. In vivo, sixty mice were utilized to assess the efficacy of JJHF in DSS-induced colitis, where the JJHF alleviated colitis, improved colon length, disease activity index (DAI), and histopathology while suppressing pro-inflammatory cytokines. Notably, MR analysis established a causal link between elevated HSPA5 expression and UC risk (OR=5.639, p=0.040). Conclusion: These findings highlight the innovative application of MR in JJHF research and underscore its multi-component, multi-target mechanisms in UC treatment, particularly through anti-inflammatory pathways and modulation of HSPA5 signaling. This study lays a scientific foundation for the clinical application and mechanistic exploration of JJHF in managing UC, offering potential advantages over standard therapies like mesalazine.

Background: Atherosclerosis (AS) plays a key role in cardiovascular diseases (CVDs) through dysregulated lipid metabolism. Flavonoids have shown promise in combatting AS due to their broad biological impacts. However, a comprehensive assessment of the methodological quality and outcomes of these studies is still lacking. This study con-ducted a rigorous systematic review and meta-analysis of research on the therapeutic potential of flavonoids in ApoE ^−/− mice, a recognized atherosclerosis model. Methods: Relevant literature was sourced from databases like PubMed, Web of Science et al. The studies were assessed for bias using the Cochrane Reviewers Handbook 6.1.0 tool. Data were ana-lyzed for heterogeneity, subgroup analysis, sensitivity analysis, and publication bias using Review Manager 5.4. The meta-analysis synthesized lipid data using standardized mean differences, employed fixed or random effects models based on heterogeneity ( I ² statistic), and conducted sensitivity and publication bias analyses. Results: A systematic search of four databases identified 11 studies meeting the inclusion criteria, all investigating flavonoids in male ApoE ^−/− mice. A meta-analysis of the extracted data, using random-effects models due to high heterogeneity ( I ² ≥ 75%), found that flavonoid administration significantly reduced blood levels of LDL-C, TC, and TG while increasing HDL-C. Sensitivity analysis confirmed the robustness of these results, though funnel plots and statistical tests indicated potential publication bias for three of the four lipid markers. All 11 studies also reported a reduction in aortic plaque area, with proposed mechanisms primarily involving antioxidant effects and the inhibition of inflammatory pathways. Conclusion: This study synthesizes pre-clinical evidence indicating that flavonoids are promising therapeutic agents for atherosclerosis, primarily through lipid modulation, plaque reduction, and pleiotropic antioxidant/anti-inflammatory mechanisms. The high heterogeneity and potential publication bias highlight the need for more standardized, high-quality animal studies to confirm these effects and better define optimal treatment protocols before clinical translation.