Anti-inflammatory Potential of Apigenin and Luteolin in Oral Mucositis: An In Silico Docking Study Targeting IL-6, NF-κB, and COX-2

Apigetrin ameliorates psoriatic inflammation and skin barrier dysfunction via NF-κB/STAT3 pathway in epidermal and dermal cell models

Combined Omeprazole and Glycyrrhiza glabra L. Extract Attenuate Ethanol-Induced Gastric Ulceration Through Modulation of TLR4/NF-κB/NLRP3 Signaling and Upregulation of PI3K/AKT/mTOR Gene Expression

Ethanol (EtOH)-induced gastric ulcer (GU) is a common model used to investigate mechanisms of mucosal injury and repair. Omeprazole (OMP) is a conventional anti-ulcer drug that effectively suppresses gastric acid secretion, but its efficacy may be enhanced by combining it with bioactive phytochemicals derived from a Glycyrrhiza glabra L. (licorice; LIQ) extract that possess potent antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the gastroprotective effects of OMP, LIQ extract, and their combined treatment against EtOH-induced GU in rats, focusing on modulation of TLR4/NF-κB/NLRP3 signaling and PI3K/AKT/mTOR gene expression. The ethanolic extract of LIQ was chemically characterized by LC-ESI-QTOF-MS/MS, and molecular docking was performed to evaluate the potential binding interactions of its major constituents with H+/K+-ATPase and COX-2. Thirty male Wistar rats were randomly allocated into control, ulcer (ULC), OMP-treated, LIQ-treated, and combined treatment groups. GU was induced by absolute EtOH. Subsequently, gastric pH, stomach coefficient, oxidative stress, inflammatory mediators, and PI3K, AKT, and mTOR gene expression were assessed. Histopathological and immunohistochemical analyses of mucosal architecture and the expression of TNF-α, caspase-3, and PCNA were performed. Coadministration of OMP and LIQ demonstrated the greatest gastroprotective activity, marked by a significant increase in gastric pH, restoration of antioxidant status, and substantial reduction in ROS, TLR4, NF-κB, and NLRP3 levels. The combined therapy significantly upregulated the expression of PI3K, AKT, and mTOR genes in comparison to ULC. Histopathological and immunohistochemical findings further demonstrated preservation of gastric mucosal integrity, reduced inflammatory cell infiltration, and decreased TNF-α, caspase-3, and PCNA immunoreactivity, indicating attenuation of mucosal injury. In conclusion, LIQ extract enhanced the gastroprotective effect of OMP against EtOH-induced GU, supporting its potential as an adjunct to OMP. Further studies are warranted to confirm the underlying molecular mechanisms.

Yangyin Shengji Powder inhibits inflammation and promotes the wound-healing in oral ulcers through regulating SIRT1/NF-κB p65 signaling pathway.

Virtual screening identifies specnuezhenide as a potential therapeutic agent for rosacea via KLK5/TLR4/NF-κB pathway inhibition and metabolic modulation

Background Rosacea is a chronic inflammatory skin condition. Excessive LL-37 is produced when serine protease kallikrein-5 (KLK5) is hyperactivated, contributing to the inflammatory response in rosacea. Thus, inhibition of KLK5 has the potential to attenuate inflammation in this condition. Reports suggest that specnuezhenide (Spe), an isomer of oleanolic acid, is effective as an anti-inflammatory agent for the treatment of inflammatory diseases. However, little is known about the role of Spe and its mechanisms in alleviating rosacea. Methods Spe was identified as a potential KLK5 inhibitor through virtual screening and molecular docking, showing high-affinity binding via hydrophobic and hydrogen-bond interactions. Rosacea was induced in mice by intradermal LL-37 injection, followed by intraperitoneal administration of Spe. The severity of skin inflammation was assessed histologically. Serum cytokines, inflammatory gene expression, and protein levels of CD31, MMP-9, CD4, and KLK5 were analyzed by ELISA, RT-qPCR, and immunofluorescence, respectively. Inhibition of the TLR4/NF-κB pathway was examined by Western blot. Untargeted metabolomics was applied to characterize alterations in serum metabolites. Results Spe markedly reduced LL-37-induced skin inflammation, decreased inflammatory cell and mast cell infiltration, decreased MMP-9 expression, and reduced CD31 fluorescence intensity and CD4+ T cell recruitment. The study demonstrated that Spe inhibited the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in serum and suppressed activation of TLR2, MMP-9, KLK5, IL-1β, IL-6, and TNF-α genes. Moreover, Spe inhibited KLK5 expression and blocked activation of the TLR4/NF-κB pathway. Metabolomics identified 43 dysregulated metabolites in rosacea, 26 of which were normalized by Spe treatment. Pathway enrichment analysis suggested that regulation of unsaturated fatty acid biosynthesis is a key mechanism underlying the effects of Spe. Conclusions This study demonstrates for the first time that Spe, a novel KLK5 inhibitor, suppresses the inflammatory response mediated by the KLK5/TLR4/NF-κB pathway, accompanied by metabolic remodeling, particularly involving the biosynthesis of unsaturated fatty acids, thereby ameliorating rosacea-like dermatitis.

Luteolin-7-O-rutinoside alleviates rheumatoid arthritis through downregulation of the PI3K/AKT/NF-κB and cell cycle signaling pathways

Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited therapeutic options, and current therapies are often associated with considerable adverse effects. Traditional Chinese medicinal plants such as Cirsium japonicum contain luteolin-7-O-rutinoside (lut-7-O-rutin), a flavonoid with reported anti-inflammatory activity. Lut-7-O-rutin is a flavonoid compound found in various medicinal plants. This study aimed to investigate the therapeutic effects of lut-7-O-rutin on RA and elucidate the underlying mechanisms using both in vitro and in vivo models, with a particular focus on the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-κB (PI3K/AKT/NF-κB) and cell cycle signaling pathways. In vitro experiments, including ELISA, Western blotting, and immunofluorescence assays, were performed to evaluate the anti-inflammatory effects of lut-7-O-rutin on the IL-1β-induced inflammatory response in fibroblast-like synoviocytes (FLSs) derived from rat knee synovium. The effects of lut-7-O-rutin on the PI3K/AKT/NF-κB and cell cycle signaling pathways were also examined. In vivo experiments were conducted to assess the therapeutic effects of lut-7-O-rutin administered by gastric gavage in collagen-induced arthritis (CIA) rats. Lut-7-O-rutin at 3.75 μg/mL significantly reduced the levels of TNF-α, IL-6, and COX-2 in IL-1β-induced FLSs. It also decreased the phosphorylation levels of key components of the PI3K/AKT/NF-κB signaling pathway, thereby attenuating inflammation. In addition, lut-7-O-rutin downregulated the expression of the cell cycle-associated proteins CDK4 and CCND and inhibited FLS proliferation. In vivo , 21 days of lut-7-O-rutin administration by gastric gavage resulted in a significant reduction in arthritis scores, organ indices, and serum inflammatory mediator levels in CIA rats. Histopathological analysis showed that lut-7-O-rutin alleviated synovial inflammation, synovial hyperplasia, and bone erosion. Immunohistochemistry (IHC) analysis further showed that lut-7-O-rutin significantly inhibited the expression of key proteins in the PI3K/AKT and cell cycle signaling pathways. These findings demonstrate that lut-7-O-rutin alleviates joint inflammation and synovial hyperplasia in RA may be mediated through inhibiting the PI3K/AKT/NF-κB signaling pathway and downregulating cell cycle-associated proteins, highlighting its potential as a therapeutic agent for RA.

Exploration of Active Components in Hou-Yan-Qing Oral Liquid and Its Alleviative Effect on Acute Pharyngitis via NRF2/NF-κB Pathways.

The Hou-Yan-Qing oral liquid (HYQ) is a popular traditional Chinese medicine for the treatment of pharyngitis. However, due to its complex composition, little attention has been directed toward the analysis of its mechanism and active components. An ammonia-induced acute pharyngitis rat model was established, with HYQ's effects and mechanism assessed via histopathology, enzyme-linked immunosorbent assay, and Western blot. Furthermore, the active components of HYQ were analyzed using HPLC and ultra performance LC (UPLC)-QTOF-MS in conjunction with an in vitro lipopolysaccharide-induced RAW264.7 cell model. Treatment with HYQ significantly reduced the levels of cytokines such as pro-inflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor α [TNF-α]) and inflammatory mediators (Prostaglandin E2 [PGE2]), inhibited the expression of cyclooxygenase-2 (COX-2), 5-LOX, p-IKKβ, p-nuclear factor-kappaB (NF-κB) and p-inhibitor of kappaBα (p-IκBα) proteins, and promoted the expression of nuclear factor-E2-related factor 2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase 1 proteins. Chemical profiling of ten batch HYQ specimens via HPLC and UPLC-QTOF-MS established characteristic fingerprints and identified 24 shared components. Using spectrum-effect relationship modeling, which employed gray relational analysis to correlate chromatographic peaks with bioactivity indices, we found that components such as 25S-Inokosterone and β-ecdysterone may be the key active components of HYQ's anti-inflammatory effect. Subsequent validation confirmed that β-ecdysterone (1-100 μM) exhibited no cytotoxicity in RAW264.7 cells. Furthermore, treatment with β-ecdysterone significantly reduced levels of pro-inflammatory cytokines (IL-6, TNF-α) and inflammatory mediators (PGE2), and inhibited the expression of COX-2, 5-LOX, p-IKKβ, p-NF-κB, and p-IκBα proteins.