Identification of TRPV1-Inhibitory Peptides from Takifugu fasciatus Skin Hydrolysate and Their Skin-Soothing Mechanisms

• Published in: Marine drugs Vol. 23; no. 5; p. 196
• Main Authors: Tang, Haiyan, Chen, Bei, Zhang, Dong, Wu, Ruowen, Qiao, Kun, Chen, Kang, Su, Yongchang, Cai, Shuilin, Xu, Min, Liu, Shuji, Liu, Zhiyu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.04.2025; MDPI
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; bioactive peptide; Capsaicin; Capsaicin receptors; Cerebrospinal fluid; Chemokines; Collagen; Cytokines; Cytokines - metabolism; Cytotoxicity; Endothelial cells; Enzymes; Enzymolysis; Granulocyte colony-stimulating factor; Granulocyte-macrophage colony-stimulating factor; Growth factors; HaCaT Cells; High performance liquid chromatography; HPLC; Humans; Hydrogen bonds; Hydrolysates; Hydrolysis; Inflammation; inflammatory response; Intercellular adhesion molecule 1; Kinases; Ligands; Lipopolysaccharides; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Mice; Molecular docking; molecular docking network pharmacology; Molecular Docking Simulation; Molecular weight; NF-kappa B - metabolism; NF-κB protein; NF-κB signaling; Peptides; Peptides - chemistry; Peptides - isolation & purification; Peptides - pharmacology; Pharmacology; Polypeptides; Protein Hydrolysates - chemistry; Protein Hydrolysates - pharmacology; Proteins; RAW 264.7 Cells; Skin; Skin - drug effects; Skin - metabolism; Stat3 protein; Synaptotagmin; Takifugu - metabolism; Takifugu fasciatus; Transient receptor potential proteins; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - metabolism; TRPV1-inhibitory peptide; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ultrafiltration; California; United States; Massachusetts; China; NF-κB signaling; Takifugu fasciatus; inflammatory response; molecular docking network pharmacology; bioactive peptide; TRPV1-inhibitory peptide
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md23050196

Skin sensitivity is increasingly prevalent, necessitating new therapeutic agents. This study screened multifunctional peptides from Takifugu fasciatus skin for transient receptor potential vanilloid 1 (TRPV1)-inhibitory and anti-inflammatory activities and investigated their mechanisms in alleviating sensitive skin (SS). A low-molecular-weight hydrolysate was prepared through enzymatic hydrolysis of T. fasciatus skin, followed by ultrafiltration, with subsequent peptide identification performed using nano-HPLC-MS/MS and molecular docking-based virtual screening. Among 20 TRPV1-antagonistic peptides (TFTIPs), QFF (T10), LDIF (T14), and FFR (T18) exhibited potent anti-inflammatory effects in (lipopolysaccharide) LPS-induced RAW 264.7 macrophages. T14 showed the strongest TRPV1 inhibition; T14 (200 μM) inhibited Ca2⁺ in capsaicin-stimulated HaCaT cells by 73.1% and showed stable binding in molecular docking, warranting further analysis. Mechanistic studies revealed that T14 suppressed NF-κB signaling by downregulating p65 protein expression, thereby reducing pro-inflammatory cytokine secretion (G-CSF, GM-CSF, ICAM-1, IL-6, TNF-α) in RAW 264.7 cells. Additionally, T14 (400 μM) inhibited ET-1 in LPS-stimulated endothelial cells by 75.0%; ICAM-1 reached 49.0%. Network pharmacology predicted STAT3, MAPK3, SPHK1, and CTSB as key targets mediating T14’s effects. These study findings suggest that T14 may be a promising candidate for skincare applications targeting SS.