Frontiers in Pharmacology
·
2025
·
IF 4.8
Shuzhen Mao,Jiahui Huang,Junyan Li,Fang Sun,Qilian Zhang,Qing Cheng,Wei Zeng,Dongya Lei,Shiyan Wang,Jing Yao
Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by mucosal damage and impaired epithelial barrier function. While glycyl-l-histidyl-l-lysine-copper (GHK-Cu) exhibits known anti-inflammatory properties, its therapeutic mechanisms in UC remain undefined. This study was designed to systematically evaluate the therapeutic potential of GHK-Cu in a dextran sulfate sodium (DSS)-induced murine model of UC, with particular emphasis on elucidating its regulatory effects on the NAD-dependent deacetylase sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.Methods: UC was induced in BALB/c mice with 3% DSS for 14 days. The protein expression levels of tight junction associated protein-1 (ZO-1), Occludin, inflammatory factors interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, SIRT1, STAT3, p-STAT3, and retinoic acid receptor-related orphan receptor gamma t (RORγt) were detected by Western blot. Histopathological changes were evaluated by Hematoxylin and Eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS). Network pharmacology and molecular docking were used to predict the core targets of GHK Cu in the treatment of UC. An in vitro UC model was also established in mouse peritoneal macrophages (MPMs) using lipopolysaccharide (LPS), and a co culture model was constructed using mouse colonic epithelial cells (MCECs) and MPMs to examine the role of GHK Cu in promoting mucosal healing. STAT3 was silenced by gene transfection technology to verify the core role of STAT3 in GHK Cu treatment of UC.Results: GHK-Cu alleviated weight loss, improved the disease activity index (DAI), reduced colonic edema and shortening, attenuated inflammatory damage, increased goblet cell numbers, suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and promoted mucosal repair. Additionally, a co-culture system of MCECs and MPMs revealed that GHK-Cu facilitated MCECs healing, impaired by DSS, by upregulating ZO-1 and Occludin expression. Subsequently, network pharmacology and molecular docking identified SIRT1 as a potential target of GHK-Cu. Results showed that GHK-Cu upregulated SIRT1 protein expression and suppressed the expression of phosphorylated p-STAT3 in colon tissue and MCECs of the co-culture model. Our findings revealed that after transfection with STAT3-targeting siRNA (siSTAT3), the stimulant effect of GHK-Cu on the healing of MCECs and the effect on the protein expression of ZO-1 and Occludin is canceled. Nevertheless, after transfection with siSTAT3, it could inhibit the expression of inflammatory factors in conjunction with GHK-Cu. Furthermore, we found that GHK-Cu could inhibit RORγt expression in the colon tissue of UC mice.Discussion: This study found that GHK-Cu demonstrated significant therapeutic effects in DSS-induced UC in mice. GHK-Cu may promote mucosal healing and enhance tight junction protein expression by regulating the SIRT1/STAT3 pathway. In addition to suppressing p-STAT3 expression, GHK-Cu may utilize additional pathways to inhibit inflammatory factors. Furthermore, GHK-Cu may reduce the number of Th17 cells. In summary, GHK-Cu may treat UC by acting on the SIRT1/STAT3 pathway.
研究领域:
药理学
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免疫学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yan Wang,Zhichao Zheng,Janak L. Pathak,Haoyu Cheng,Sizhen Huang,Zi Fu,Ping Li,Lihong Wu,Huade Zheng
Biocompatible, antibacterial, anti-inflammatory, and tissue regenerative smart dressings are in urgent need for infected skin wound repair in clinics. Portable in situ 3D-electrospun technology has the great advantage of direct deposition of required smart dressing on wound surfaces. Here, we fabricated a copper peptide (GHK-Cu) and quaternium-73 (Pionin) dual-drug-loaded polyvinyl butyral (PVB)/polyvinylpyrrolidone (PVP) smart nanofibers dressing using in-situ electrospinning technology for skin wound repair. The physicochemical properties and biological activities of smart dressing were extensively analyzed. In vivo biocompatibility, anti-oxidant, anti-inflammatory, and antimicrobial activities of smart dressing were analyzed during wound healing. Stable and homogeneous PVB/PVP nanofiber smart dressing with uniformly distributed GHK-Cu and Pionin and anabolic biological activities was obtained. Biocompatible smart dressing gave a sustained release of GHK-Cu and Pionin, promoted the migration and adhesion of dermal fibroblasts and keratinocytes, and showed anti-oxidant and anti-apoptotic effects in vitro and in vivo. Smart dressing exerted anti-inflammatory properties via M1 to M2 macrophage phenotype switching and effectively promoted wound healing. Pionin released from smart dressing not only killed but also inhibited the expression and delivery of virulence factor expression and bacteria adhesion. During wound healing, smart dressing promoted the proliferation of cells in the epidermal tissue, epithelial tissue remodeling, granulation tissue growth, neovascularization, and M2 macrophage polarization. Moreover, this smart dressing scavenged excess reactive oxygen species, increased SOD3 and SIRT1 expression, and repaired peroxidized tissue, consequently promoting wound healing. In summary, our results indicate that GHK-Cu/Pionin-loaded in situ electrospun PVB/PVP smart dressing promotes wound healing via anti-oxidant, anti-inflammatory, antimicrobial, and tissue regenerative effects, suggesting clinical application of this smart dressing for complicated skin wound healing.
研究领域:
生物医学工程
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伤口愈合
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材料科学
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Die Hu,Xuexun Zhang,Shiwen Gong,Wentao Ma,Bo Cheng,Jing Yang,Lesan Yan,Binbin Li,Tong Qiu,Xinyu Wang
With the wide application of soft tissue fillers, implant material-induced inflammatory reactions have become a key factor affecting the therapeutic efficacy. This study developed an injectable filler with enhanced anti-inflammatory and antioxidant effects by adsorbing glycyl-L-histidyl-L-lysine copper complex (GHK-Cu) onto hydroxyapatite microspheres (HAPs), marking the first combination of HAPs and GHK-Cu to address inflammation caused by soft tissue fillers. GHK-Cu was successfully loaded onto HAPs by electrostatic adsorption. HAPs were then mixed with carboxymethyl cellulose (CMC), glycerol (GLY), and water to form GHK-Cu@CMHA gel. The study focus on the effective combination of HAPs as a carrier for sustained GHK-Cu delivery and the anti-inflammatory properties of GHK-Cu. GHK-Cu@CMHA exhibits sustained release properties for 7 days, which ensures prolonged therapeutic effects, minimizes peptide waste and reduces injection frequency, with good flowability and injectability. In the model of LPS-induced inflammation model in vivo and in vitro, GHK-Cu@CMHA gel reduced levels of inflammatory factors and Reactive oxygen species (ROS) levels decreased, while superoxide dismutase (SOD) activity was enhanced. In this process, H&E staining and Masson staining revealed significant collagen deposition. These findings further confirm that GHK-Cu@CMHA is a novel injectable soft tissue filler with good anti-inflammatory and antioxidant properties, which holds well potential for inflammation inhibition.
研究领域:
生物材料
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组织工程
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生物医学工程
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药剂学
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炎症研究
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2025
·
IF 9.6
Han Chen,Pu Yang,Ping Xue,Songjie Li,Xin Dan,Yang Li,Lanjie Lei,Xing Fan
The field of infected wound management continues to face challenges, and traditional methods used to cope with wounds include debridement, gauze coverage, medication, and others. Currently, synthetic and natural biomaterials are readily available today, enabling the creation of new wound dressings that substantially enhance wound healing. Considerable attention is being paid to hydrogels based on natural materials, which have good biocompatibility and degradability properties, while exhibiting higher similarity to natural extracellular matrix as compared to synthetic materials. In this study, we extracted the active ingredients of oxidized konjac glucomannan (OKGM) and fresh egg white (EW) from 2 foods, konjac, and egg, respectively, and formed a self-repairing hydrogel based on the cross-linking of a Schiff base. Subsequently, a natural active peptide, glycyl-l-histidyl-l-lysine-Cu (GHK-Cu), was loaded, and an all-natural composite hydrogel dressing, EW/OKGM@GHK-Cu (GEK), was developed. The GEK hydrogel, exhibiting both antibacterial and anti-inflammatory properties, plays a hemostatic role by adhering to tissues and promoting neovascularization and serves as an optimal dressing for skin regeneration. Taken together, GEK hydrogel dressings derived from natural food sources therefore constitute an efficient and cost-effective strategy for managing infected wound healing and have significant potential for clinical application and transformation.
研究领域:
生物材料学
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伤口愈合
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药剂学
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DOI
PubMed
高影响因子
Biosensors-Basel
·
2026
·Vol. 16
·期 4
·217
·
IF 6.2
Jiang-Shan Chen,Huan Zhu,Tong-Qing Chai,Feng-Qing Yang
Laccase plays an important role in the detection and degradation of phenolic compounds, but it is limited by its cost and stability. In this study, the laccase-like property of copper peptide (GHK-Cu) has been revealed. In terms of enzymatic reaction kinetics, GHK-Cu has aVmaxof 1.735 × 10−4mM·s−1and aKmof 0.061 mM, demonstrating good substrate affinity and excellent catalytic efficiency. Then, a colorimetry was developed for rapid detection of epinephrine (EP) and 2-aminophenol (2-AP). The linear response range of EP is 20–240 μM, with a limit of detection (LOD) of 9.5 μM. The linear response ranges of 2-AP are 14–100 μM (in ultrapure water) and 2–120 μM (in seawater), with LODs of 2.56 μM and 1.65 μM. In addition, combined with a smartphone platform, a cotton-based sensor has been developed for the detection of 2-AP in seawater. The linear response ranges are 0–0.2 mM and 0.2–1 mM, with LOD of 0.033 mM. The structure of GHK-Cu provides a reference for the development of novel laccase mimetic enzymes. The constructed colorimetry offers an option for the rapid detection of phenolic compounds, and the developed cotton-based sensor enabled rapid and portable detection of 2-AP.
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Yan Wang,Jialiang Lin,Zihao Yu,Jinbo Cheng,Jianhua Cheng,Weikang Cui
Peptides are recognized as highly effective and safe bioactive ingredients. However, t their practical application is limited and hampered by harsh conditions for practical drug delivery. Hence, a novel peptide nanocarrier of copper peptide (GHK-Cu) encapsulation developed by liposome technology combined with the classical Chinese concept of rigidity and flexibility. Different polyols were selected as modification ligands for phospholipid bilayers to construct a nano drug-carrying system with high loading rate, good stability and biocompatibility. In vitro, this complex not only significantly retarded the release ability of copper peptides, but also enabled copper peptides to be effectively resistant to enzymatic degradation. Furthermore, cellular experiments showed that this system mainly regulates Nrf2, SIRT1, and PEG2/COX-2-related signaling pathways, thus effectively counteracting cellular inflammation, senescence, and apoptosis from oxidative damage. Interestingly, a green, non-toxic, efficient and convenient antioxidant system was developed for the prevention and deceleration of skin aging.
研究领域:
药剂学
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纳米技术
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皮肤病学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2026
·
IF 5.4
Shunyu Chen,Mengting Lei,Pei Liu,Xiufeng Xiao
Chronic wound healing is often impaired by persistent pathogenic infection, excessive oxidative stress, and insufficient angiogenic drive. In this study, a multifunctional injectable hydrogel dressing (Gel/ODex/MT/GHK-Cu) was developed based on a dynamic chemical network to accelerate skin tissue regeneration through the synergistic effects of photothermal antibacterial therapy and biochemical signaling. The system utilizes dynamic Schiff base crosslinking between gelatin (Gel) and oxidized dextran (ODex) as the structural framework, integrating MXene@TiO 2 (MT) heterojunction nanosheets and copper peptide (GHK-Cu) as functional units. Results demonstrated that the hydrogel possessed excellent rheological properties, self-healing capacity, and tissue adhesiveness (with adhesion strength sufficient to withstand various skin movements), with a swelling ratio exceeding 200% for effective exudate management. Under 808 nm near-infrared (NIR) irradiation, the MT heterojunction nanosheets exhibited significant photothermal conversion capability, raising the local temperature above 45 °C within 15 min, achieving efficient ablation (>99%) of Staphylococcus aureus and Escherichia coli through the synergy of hyperthermia and the physical-mechanical disruption of bacterial membranes. Meanwhile, the sustained release of Cu 2 + from GHK-Cu provided outstanding antioxidant activity and significantly enhanced the migration of human umbilical vein endothelial cells. In vivo evaluations in a mouse full-thickness skin defect model confirmed that the hydrogel combined with NIR treatment significantly shortened wound closure time and promoted re-epithelialization, collagen deposition, and the formation of functional hair follicles. By establishing an integrated platform for physical protection, precise ablation, and bio-inspired repair, this study offers a promising advanced strategy for the clinical management of chronic infected wounds. Download: Download high-res image (126KB) Download: Download full-size image A multifunctional injectable hydrogel dressing was developed via Schiff base crosslinking of gelatin and oxidized dextran, incorporating MXene@TiO₂ nanosheets and GHK‑Cu. The hydrogel shows excellent photothermal antibacterial activity, anti-inflammatory effect, and sustained Cu²⁺ release to promote angiogenesis and L929 cell proliferation. Combined with NIR irradiation, the hydrogel significantly accelerates full‑thickness wound healing in mice by enhancing re‑epithelialization, angiogenesis, collagen deposition, and hair follicle regeneration.
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高影响因子
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