Xanthium strumarium L. extract attenuates TNF-α/IFN-γ- stimulated inflammation and promotes hyaluronan production on HaCaT keratinocytes

Bioactive dicaffeoylquinic acid-enriched callus extract of Weigela subsessilis inhibits TNF-α/IFN-γ-induced keratinocyte inflammation via MAPK and NF-κB pathways

This study highlights WSCE as a potential anti-dermatitis agent, suppressing pro-inflammatory mediators in T+I-stimulated keratinocytes via MAPK and NF-κB regulation and position WSCE as a promising candidate for ISD management.

Benzyl isothiocyanate alleviates endotoxin-induced uveitis in association with LOX-1 downregulation to modulate JAK2-STAT3 signaling, endoplasmic reticulum stress and apoptosis.

Uveitis is a sight-threatening inflammatory ocular disorder. Benzyl isothiocyanate (BITC) exhibits potent anti-inflammatory pharmacological activity. This research was designed to explore the therapeutic mechanism of BITC in acute uveitis (AU). We established a mouse model of endotoxin-induced uveitis (EIU) to evaluate the therapeutic efficacy of BITC. Results demonstrated that BITC (20 mg/kg) significantly alleviated intraocular inflammation and tissue damage in EIU mice, while inhibiting microglial activation, JAK2/STAT3 signaling pathway activation, and proinflammatory cytokine secretion. BITC (4 and 8 μM) also decreased levels of nitric oxide, reactive oxygen species, IL-1β, TNF-α, and IL-6 induced by LPS in BV2 cells. Furthermore, BITC significantly suppressed the endoplasmic reticulum (ER) stress markers PERK and eIF-2α phosphorylation, and the expression of GRP78, ATF4, CHOP in vivo and in vitro. It also reduced apoptosis and caspase-3 activation, and increased the BCL2/BAX ratio. Notably, BITC downregulated lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression. Overexpression of LOX-1 in BV2 cells markedly reversed the protection actions of BITC on JAK-STAT pathway, inflammation, ER stress, and apoptosis. Collectively, this study reveals that BITC ameliorates the progression of AU. Its protective action is closely coupled with the downregulation of LOX-1, leading to the inhibition of JAK2/STAT3 signaling pathway and the attenuation of ER stress and apoptosis.

Ethanolic Extract of Sophora moorcroftiana Seeds Attenuates LPS-Induced Inflammation and Oxidative Stress in RAW 264.7 Macrophages via Modulation of the p62/Keap1/Nrf2 Signaling Pathway

The ethanolic extract of SMS attenuated LPS-induced inflammatory and oxidative stress responses in RAW 264.7 macrophages, suggesting effects may be associated with the suppression of inflammatory mediator production, reduction in the cellular oxidative stress burden and modulation of proteins involved in cellular stress responses and antioxidant defense.

Ribes fasciculatum Leaf Water Extract Enhances Macrophage Immune Responses via TLR4-Mediated JNK and NF-κB Activation in RAW264.7 Cells

This study investigated the immunostimulatory activity and underlying mechanism of Ribes fasciculatum leaf water extract in RAW264.7 macrophages. Among extracts prepared using water or ethanol-containing solvents, only the water extract induced NO production. Further evaluation of extraction temperature and time identified the extract prepared at 20°C for 24 h (RFL-DW20) as the most active sample under the tested conditions, with NO-inducing activity increasing after 12 h of extraction and reaching a plateau by 24 h. RFL-DW20 increased NO and PGE2 production, upregulated iNOS and COX-2 expression, and enhanced IL-6 and TNF-α production without cytotoxicity. RFL-DW20 also increased IL-1β mRNA expression but did not significantly alter extracellular IL-1β levels. RFL-DW20 also increased neutral red uptake, indicating enhanced macrophage functional activity. The immunostimulatory effects of RFL-DW20 were strongly inhibited by TAK-242, SP600125, and BAY 11-7082, suggesting the involvement of TLR4, JNK, and NF-κB signaling. RFL-DW20 activated MAPK and NF-κB signaling, including rapid IκBα phosphorylation/degradation and p65 phosphorylation, while pharmacological inhibition identified JNK and NF-κB as major functional mediators of the NO response. TAK-242 markedly suppressed RFL-DW20-induced JNK and p65 phosphorylation. Ethanol precipitation further enriched its NO-inducing activity. These findings suggest that RFL-DW20 activates macrophages through the TLR4/JNK/NF-κB signaling axis and may serve as a natural immune-stimulating material.

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

Methanolic extracts of Amaranthus spinosus (Linn.) mitigate TAA-Induced hepatic fibrosis through modulation of inflammatory cytokines and profibrotic signalling.

BACKGROUND Persistent oxidative stress disrupts intrahepatic immune homeostasis, leading to cytokine dysregulation and fibrogenic progression in the liver. This study investigated the immunomodulatory and antifibrotic effects of methanolic extracts of Amaranthus spinosus (leaf, stem, and root) in a thioacetamide (TAA)-induced murine model of hepatic fibrosis. METHODS Swiss albino mice were administered TAA (150 mg/kg, intraperitoneally, thrice weekly for 8 weeks) to induce fibrosis, followed by oral treatment with plant extracts (250 mg/kg) for 15 consecutive days. Hepatocyte-specific cytokine expression (IL-6, TNF-α, IL-12, TGF-β, and IL-10) was evaluated by flow cytometry and quantitative real-time PCR, and immunohistochemistry was used to assess COX-2 and iNOS expression. RESULTS TAA administration resulted in significant upregulation of pro-inflammatory (IL-6, TNF-α, IL-12) and profibrotic (TGF-β) cytokines, along with elevated IL-10 expression, indicating dysregulated immune homeostasis. Extract treatment significantly attenuated (p < 0.01) these alterations in a fraction-dependent manner, with the root extract exhibiting the highest efficacy, restoring cytokine levels to near physiological baseline. These findings were corroborated at the transcriptional level by qPCR. Additionally, extract-treated groups showed significant downregulation of COX-2 and iNOS expression, reflecting reduced oxidative and nitrosative stress. In contrast, TAA withdrawal alone, or in combination with the vehicle control, failed to effectively normalize inflammatory markers. CONCLUSIONS Collectively, these results demonstrate that A. spinosus exerts potent antifibrotic activity by modulating hepatocyte-driven cytokine networks and suppressing redox-sensitive inflammatory pathways. The root extract, in particular, shows strong therapeutic potential as a multi-target agent capable of disrupting the inflammation-fibrosis axis in chronic liver injury.