Scholarlink

Background <p>Animal venoms are rich in bioactive peptides with potential therapeutic properties. Among marine toxins, jellyfish venoms are underexplored for anti-inflammatory applications. This study aims to identify and evaluate a peptide derived from the jellyfish toxin CfTX-B, for its anti-inflammatory potential.</p> Methods <p>Peptide selection was conducted through an integrated computational–experimental workflow comprising PeptideRanker bioactivity prediction, ToxinPred toxicity screening, SwissADME pharmacokinetic evaluation, and multi-target molecular docking against NLRP3, caspase-1, XO, and IL-1β, followed by LC-MS/MS confirmation of proteolytic stability. The peptide’s antioxidant activity was validated through XO inhibition assays. Cytotoxicity and anti-inflammatory effects were tested in human dermal fibroblasts (HDFs) co-stimulated with lipopolysaccharide (LPS) and monosodium urate (MSU) crystals. FITC-labeling studies assessed intracellular peptide uptake. Further, the inflammation suppressing effects of the peptide were studied on in vivo rat model of gouty arthritis.</p> Results <p>The CfTX-B derived tetrapeptide (WPAW) revealed highest predicted bioactivity scores, favorable ADMET characteristics, and resistance to simulated gastrointestinal digestion. The peptide also showed strong binding to NLRP3, caspase-1, XO, and low predicted toxicity. XO inhibition assays confirmed antioxidant activity. In HDFs, the peptide showed no cytotoxicity up to 125 µM. Treatment with peptide significantly reduced nitric oxide (14.05 ± 0.24 µM) and reactive oxygen species (0.32 ± 0.009 RFI). ELISA revealed lowered IL-1β levels (53.54 ± 3.05 pg/ml). Protein expression studies showed downregulation of NLRP3, and pP65 levels, indicating effective suppression of inflammasome activation. The peptide reduced serum XO activity, IL-1β levels and suppressed joint inflammation in gout induced rats.</p> Conclusions <p>The tetrapeptide derived from jellyfish venom, exhibits strong anti-inflammatory and antioxidant activity through NLRP3 inflammasome inhibition. These results support its potential for development as a therapeutic for chronic inflammatory diseases.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Inflammation suppressing activity of jellyfish toxin-derived peptide via downregulation of ROS/NF-κB/NLRP3 signaling in LPS/MSU induced fibroblasts in vitro and in vivo gouty arthritis model

  • 期刊论文

  • 发表日期：

    2026年2月9日

查看全文
  • Akshad Balde,
  • Rasool Abdul Nazeer

摘要

Background

Animal venoms are rich in bioactive peptides with potential therapeutic properties. Among marine toxins, jellyfish venoms are underexplored for anti-inflammatory applications. This study aims to identify and evaluate a peptide derived from the jellyfish toxin CfTX-B, for its anti-inflammatory potential.

Methods

Peptide selection was conducted through an integrated computational–experimental workflow comprising PeptideRanker bioactivity prediction, ToxinPred toxicity screening, SwissADME pharmacokinetic evaluation, and multi-target molecular docking against NLRP3, caspase-1, XO, and IL-1β, followed by LC-MS/MS confirmation of proteolytic stability. The peptide’s antioxidant activity was validated through XO inhibition assays. Cytotoxicity and anti-inflammatory effects were tested in human dermal fibroblasts (HDFs) co-stimulated with lipopolysaccharide (LPS) and monosodium urate (MSU) crystals. FITC-labeling studies assessed intracellular peptide uptake. Further, the inflammation suppressing effects of the peptide were studied on in vivo rat model of gouty arthritis.

Results

The CfTX-B derived tetrapeptide (WPAW) revealed highest predicted bioactivity scores, favorable ADMET characteristics, and resistance to simulated gastrointestinal digestion. The peptide also showed strong binding to NLRP3, caspase-1, XO, and low predicted toxicity. XO inhibition assays confirmed antioxidant activity. In HDFs, the peptide showed no cytotoxicity up to 125 µM. Treatment with peptide significantly reduced nitric oxide (14.05 ± 0.24 µM) and reactive oxygen species (0.32 ± 0.009 RFI). ELISA revealed lowered IL-1β levels (53.54 ± 3.05 pg/ml). Protein expression studies showed downregulation of NLRP3, and pP65 levels, indicating effective suppression of inflammasome activation. The peptide reduced serum XO activity, IL-1β levels and suppressed joint inflammation in gout induced rats.

Conclusions

The tetrapeptide derived from jellyfish venom, exhibits strong anti-inflammatory and antioxidant activity through NLRP3 inflammasome inhibition. These results support its potential for development as a therapeutic for chronic inflammatory diseases.

Graphical abstract