Identification of TRPV1-Inhibitory Peptides from <i>Takifugu fasciatus</i> Skin Hydrolysate and Their Skin-Soothing Mechanisms

Skin sensitivity is increasingly prevalent, necessitating new therapeutic agents. This study screened multifunctional peptides from <i>Takifugu fasciatus</i> skin for transient receptor potential vanilloid 1 (TRPV1)-inhibitory and anti-inflammatory activities and investigated their mecha...

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Main Authors: Haiyan Tang, Bei Chen, Dong Zhang, Ruowen Wu, Kun Qiao, Kang Chen, Yongchang Su, Shuilin Cai, Min Xu, Shuji Liu, Zhiyu Liu
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/23/5/196
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author Haiyan Tang
Bei Chen
Dong Zhang
Ruowen Wu
Kun Qiao
Kang Chen
Yongchang Su
Shuilin Cai
Min Xu
Shuji Liu
Zhiyu Liu
author_facet Haiyan Tang
Bei Chen
Dong Zhang
Ruowen Wu
Kun Qiao
Kang Chen
Yongchang Su
Shuilin Cai
Min Xu
Shuji Liu
Zhiyu Liu
author_sort Haiyan Tang
collection DOAJ
description Skin sensitivity is increasingly prevalent, necessitating new therapeutic agents. This study screened multifunctional peptides from <i>Takifugu fasciatus</i> 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 <i>T. fasciatus</i> 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 Ca<sup>2</sup>⁺ 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.
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spelling doaj-art-e7e5a2ee20df423b8bc57f01a2b35c2d2025-08-20T03:14:39ZengMDPI AGMarine Drugs1660-33972025-04-0123519610.3390/md23050196Identification of TRPV1-Inhibitory Peptides from <i>Takifugu fasciatus</i> Skin Hydrolysate and Their Skin-Soothing MechanismsHaiyan Tang0Bei Chen1Dong Zhang2Ruowen Wu3Kun Qiao4Kang Chen5Yongchang Su6Shuilin Cai7Min Xu8Shuji Liu9Zhiyu Liu10College of Food Sciences & Technology, Shanghai Ocean University, Shanghai 201306, ChinaKey Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, National Research and Development Center for Marine Fish Processing, Fisheries Research Institute of Fujian, Xiamen 361013, ChinaCollege of Food Sciences & Technology, Shanghai Ocean University, Shanghai 201306, ChinaCollege of Chemical Engineering, Hua Qiao University, Xiamen 362021, ChinaKey Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, National Research and Development Center for Marine Fish Processing, Fisheries Research Institute of Fujian, Xiamen 361013, ChinaMimask (Xiamen) Bio-Tech Co., Ltd., Xiamen 361000, ChinaKey Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, National Research and Development Center for Marine Fish Processing, Fisheries Research Institute of Fujian, Xiamen 361013, ChinaKey Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, National Research and Development Center for Marine Fish Processing, Fisheries Research Institute of Fujian, Xiamen 361013, ChinaKey Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, National Research and Development Center for Marine Fish Processing, Fisheries Research Institute of Fujian, Xiamen 361013, ChinaKey Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, National Research and Development Center for Marine Fish Processing, Fisheries Research Institute of Fujian, Xiamen 361013, ChinaKey Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, National Research and Development Center for Marine Fish Processing, Fisheries Research Institute of Fujian, Xiamen 361013, ChinaSkin sensitivity is increasingly prevalent, necessitating new therapeutic agents. This study screened multifunctional peptides from <i>Takifugu fasciatus</i> 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 <i>T. fasciatus</i> 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 Ca<sup>2</sup>⁺ 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.https://www.mdpi.com/1660-3397/23/5/196<i>Takifugu fasciatus</i>TRPV1-inhibitory peptideinflammatory responsebioactive peptideNF-κB signalingmolecular docking network pharmacology
spellingShingle Haiyan Tang
Bei Chen
Dong Zhang
Ruowen Wu
Kun Qiao
Kang Chen
Yongchang Su
Shuilin Cai
Min Xu
Shuji Liu
Zhiyu Liu
Identification of TRPV1-Inhibitory Peptides from <i>Takifugu fasciatus</i> Skin Hydrolysate and Their Skin-Soothing Mechanisms
Marine Drugs
<i>Takifugu fasciatus</i>
TRPV1-inhibitory peptide
inflammatory response
bioactive peptide
NF-κB signaling
molecular docking network pharmacology
title Identification of TRPV1-Inhibitory Peptides from <i>Takifugu fasciatus</i> Skin Hydrolysate and Their Skin-Soothing Mechanisms
title_full Identification of TRPV1-Inhibitory Peptides from <i>Takifugu fasciatus</i> Skin Hydrolysate and Their Skin-Soothing Mechanisms
title_fullStr Identification of TRPV1-Inhibitory Peptides from <i>Takifugu fasciatus</i> Skin Hydrolysate and Their Skin-Soothing Mechanisms
title_full_unstemmed Identification of TRPV1-Inhibitory Peptides from <i>Takifugu fasciatus</i> Skin Hydrolysate and Their Skin-Soothing Mechanisms
title_short Identification of TRPV1-Inhibitory Peptides from <i>Takifugu fasciatus</i> Skin Hydrolysate and Their Skin-Soothing Mechanisms
title_sort identification of trpv1 inhibitory peptides from i takifugu fasciatus i skin hydrolysate and their skin soothing mechanisms
topic <i>Takifugu fasciatus</i>
TRPV1-inhibitory peptide
inflammatory response
bioactive peptide
NF-κB signaling
molecular docking network pharmacology
url https://www.mdpi.com/1660-3397/23/5/196
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