18β-Glycyrrhetinic acid monoglucuronide (GAMG) alleviates radiation-induced lung injury in mice by regulating macrophage polarization through the NF-κB signaling pathway.

Norcantharidin attenuates amiodarone-induced pulmonary fibrosis via modulating miRNA-30a/GSK-3β/β-catenin and oxidative-inflammatory pathways.

Treatment with Biaoxu Ganmao Granules ameliorates cyclophosphamide-induced immunosuppression in mice: Paeoniflorin-associated modulation of the TLR4/NF-κB pathway.

BXGG partially reversed CTX-associated reductions in body weight, thymus and spleen indices and partially restored serum interleukin-2, interleukin-4 (IL-4), and interferon-gamma (IFN-γ) levels, and white blood cell, lymphocyte, platelet, and reticulocyte counts.

Secoisolariciresinol diglucoside alleviates inflammatory injury in osteoarthritis chondrocytes through ERBB2-associated JAK2/STAT3 signaling: network pharmacology and experimental validation

Cartilage injury is a hallmark of osteoarthritis (OA). erb-B2 receptor tyrosine kinase 2 (ERBB2) has been reported to be involved in mediating the therapeutic effects of polyphenols in orthopedic diseases. This study aimed to investigate the protective effects and underlying mechanisms of action of ERBB2 in OA chondrocytes. Bioinformatics analysis and molecular docking were used to predict the binding relationship between ERBB2 and the polyphenolic compound, secoisolariciresinol diglucoside (SDG). ATDC5 cells were induced with insulin-transferrin-selenium (ITS), followed by lipopolysaccharide (LPS) exposure to mimic OA inflammation, and treated with SDG. Cell viability, collagen II expression, apoptosis, interleukin 6 (IL-6)/Tumor Necrosis Factor-α (TNF-α) secretion, and malondialdehyde (MDA)/superoxide dismutase (SOD) levels were evaluated using cell counting kit-8 (CCK-8), immunofluorescence, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and commercial kits. Matrix metalloproteinase 13 (MMP13) and ERBB2 mRNA levels were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Extracellular matrix integrity was assessed by toluidine blue staining. The predicted SDG-ERBB2 interaction was validated using a cellular thermal shift assay (CETSA). Western blotting was performed to assess the expression of ERBB2 and JAK2/STAT3. Rescue experiments with ERBB2 overexpression or colivelin (a JAK/STAT activator) treatment confirmed the involvement of this pathway. SDG dose-dependently reversed the LPS-induced reduction in cell viability and collagen II expression, while suppressing apoptosis, IL-6/TNF-α secretion, and MDA levels, and increasing SOD activity. SDG significantly reduced MMP13 mRNA levels and enhanced extracellular matrix proteoglycan deposition, indicating the preservation of matrix integrity. ERBB2 has been identified as a candidate target for SDG. SDG inhibits ERBB2 protein expression and reduces JAK2 and STAT3 phosphorylation ERBB2 overexpression and colivelin treatment abrogated the protective effects of SDG on cell viability, collagen II expression, apoptosis, inflammation, and oxidative stress, as well as its suppression of MMP13 and preservation of matrix integrity. SDG protects chondrocytes against LPS-induced inflammatory injury by targeting ERBB2 and suppressing the downstream JAK2/STAT3 signaling pathway. These findings provide mechanistic evidence supporting the chondroprotective potential of SDG under inflammatory conditions and suggest that ERBB2/JAK2/STAT3 signaling may represent a potential therapeutic target in OA.

Ac EL-6 Reduces Methylglyoxal-Associated Glycation and NF-κB-Mediated Inflammatory Responses While Supporting Acute Skin Repair

Lycorine ameliorates diabetic nephropathy by targeting RAGE and inhibiting the HMGB1/RAGE/NF-κB signaling axis

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease. Chronic inflammation plays a pivotal role in the pathogenesis of DN. Lycorine (LY), a complex tetracyclic pyrrolo[de]phenanthridine alkaloid derived from the Amaryllidaceae family, possesses notable anti-inflammatory activity, yet its therapeutic potential in DN remains insufficiently defined. We evaluated the renoprotective effects of LY both in vivo and in vitro. Streptozotocin (STZ)-induced diabetic mice were treated with LY, and renal function and histopathological alterations were assessed. In vitro, human renal tubular epithelial HK-2 cells were exposed to high glucose plus palmitic acid (HG + PA) with or without LY. RNA-seq analysis was performed to identify LY-regulated pathways. Molecular docking, surface plasmon resonance (SPR) assay, and cellular thermal shift assay (CETSA) were used to evaluate the interaction between LY and receptor for advanced glycation end products (RAGE). RAGE siRNA-mediated knockdown was further conducted to determine whether RAGE is required for the protective effects of LY. Activation of the HMGB1/RAGE/NF-κB signaling axis and associated inflammatory mediators was analyzed by Western blotting and RT-PCR. LY markedly alleviated renal injury in STZ-induced diabetic mice, as evidenced by reduced albuminuria, improved renal function, and attenuated renal fibrosis, apoptosis, oxidative stress, and inflammation. Notably, LY did not significantly alter blood glucose levels or body weight, indicating that its renoprotective effect was independent of glycemic control. In HG + PA-treated HK-2 cells, LY significantly suppressed apotosis, oxidative stress, and inflammatory cytokine expression. Mechanistically, RNA-seq analysis identified AGE-RAGE and NF-κB signaling pathways as key pathways modulated by LY. Molecular docking, SPR, and CETSA confirmed that LY directly interacted with RAGE. Moreover, RAGE knockdown largely abolished the additional protective effects of LY, supporting RAGE as a critical molecular target. LY inhibited HMGB1/RAGE-mediated NF-κB activation, as reflected by reduced HMGB1, RAGE, p-p65, and p-IκBα levels. LY ameliorates diabetic nephropathy without affecting blood glucose levels by directly targeting RAGE and suppressing the HMGB1/RAGE/NF-κB signaling axis. These findings identify LY as a potential RAGE-targeting therapeutic candidate for inflammation-driven diabetic kidney injury.

Taxamairin B inhibits inflammatory response by suppressing activation of PI3K/AKT/NF-kappaB signaling in a mouse model of transfusion-related acute lung injury.

BACKGROUND Transfusion-related acute lung injury (TRALI) is a serious adverse event of blood transfusion, characterized by pulmonary inflammation, edema, and neutrophil infiltration. This study aimed to explore the protective effects of taxamairin B (Taxa B), a natural component derived from Taxusmairei, on lung damage and inflammation in a mouse model of TRALI. METHODS A TRALI mouse model was established through sequential injection of lipopolysaccharide (LPS) and major histocompatibility complex (MHC) antibody. Extravascular lung water, extravascular plasma equivalents, lung weight/dry ratio, and protein concentration in bronchoalveolar lavage fluid (BALF) were measured. Histopathological changes were performed using hematoxylin-eosin staining. Neutrophil extracellular trap (NET) formation was evaluated by immunofluorescence staining. ELISA was conducted to quantify inflammatory cytokine levels in BALF and NET levels in mouse blood samples. Protein levels of PI3K, Akt, and NF-κB, as well as their phosphorylated levels, were measured by Western blotting. RESULTS Taxa B improved the survival of model mice by mitigating lung injury, reducing pulmonary edema, and attenuating lung tissue damage. Moreover, Taxa B suppressed NET formation in lung tissues and blood samples of model mice. Following TRALI induction, the levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) were significantly elevated while IL-10 levels were reduced, and these alterations were counteracted by Taxa B administration. Importantly, Taxa B inhibited the phosphorylated levels of PI3K, Akt, NF-κB, and IκBα in lung tissues of model mice. CONCLUSION Taxa exerts anti-inflammatory effects in a mouse model of TRALI by inhibiting the PI3K/Akt/NF-κB signaling.