Search Results (136)

Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article

Estrogen-related receptor γ (ERRγ) has been reported to regulate various inflammation-related diseases. Herein, we attempted to evaluate the effects of DN200434 as a modulator for ERRγ in mice with atopic dermatitis (AD). Levels of mRNA and protein expression for ERRγ were evaluated in normal and DNCB-induced AD-diagnosed skin. The effects of DN200434 on the chemokines, inflammatory cytokines, and AKT/MAPK/NFκB pathway signaling were investigated in TNF-α/IFN-γ-treated HaCaT cells. DNCB-induced AD mice received DN200434 intraperitoneally for 10 days. Epidermal thickness at the dorsal aspect of the inflamed skin, spleen index, serum IgE levels, and proinflammatory cytokine levels in the skin lesions were measured. Histopathological evaluations, including assessments of epidermal hyperplasia, dermal inflammation, hyperkeratosis, folliculitis, and mast cell counts, were performed to confirm diagnostic features. Significant elevations in ERRγ expression at the RNA and protein levels were observed in DNCB-induced AD lesions. DN200434 suppressed chemokine and inflammatory cytokine expression and inhibited the elevated phosphorylation levels of AKT, ERK, p38, and NFκB in TNF-α/IFN-γ-treated HaCaT cells. Treatment with DN200434 alleviated DNCB-induced AD symptoms. The histopathological score and levels of infiltrated mast cells were also markedly lower in DN200434-treated AD mice than in vehicle-treated AD mice. Consistently, DN200434 reduced the serum IgE level and mRNA expression of TNFα and IL-6 in AD-diagnosed lesions. Collectively, our findings indicated the feasibility of ERRγ as a therapeutic target for the regulation of AD and that DN200434 can be a useful therapeutic agent in treating AD. Full article

Helianthus annuus L. (H. annuus) receptacles, a major agricultural by-product generated during seed processing, are currently underutilized. This study aimed to explore the valorization potential of this by-product by extracting H. annuus receptacles total polysaccharides (HRTP) and characterizing their potential as natural ingredients in ultraviolet (UV)-protective cosmetics. A new purified polysaccharide named H. annuus receptacles polysaccharide-1 (HRP-1) was isolated, likely exhibiting a backbone of alternating →4)-α-D-GalA-(1→ and →4)-α-D-GalA(6-OCH₃)-(1→ units, with a weight-average molecular weight (Mw) of 163 kDa. HRTP demonstrated significant protective effects against UV-induced damage in human immortalized keratinocyte (HaCaT) cells by suppressing intracellular reactive oxygen species (ROS) levels and downregulating MAPK-p38/ERK/JNK pathways, thereby inhibiting inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) and matrix metalloproteinases (MMP-1, MMP-3, and MMP-9). Additionally, HRTP exhibited moisturizing properties. These findings highlight H. annuus receptacle polysaccharides as sustainable, bioactive ingredients for eco-friendly sunscreen formulations, providing a practical approach to converting agricultural by-products into high-value industrial biomaterials. Full article

Dendrobium, a prominent genus in the Orchidaceae family, has generated significant research attention due to its demonstrated biological potential, particularly its notable anti-inflammatory and antioxidant activities. In this study, two fractions of fermented Dendrobium officinale polysaccharides (FDOPs) were successfully isolated through a multi-stage purification strategy including gradient ethanol precipitation, gel column chromatography, and ion exchange chromatography with Lactobacillus reuteri CCFM863. Structural characterization revealed that both Dendrobium officinale polysaccharide fractions consisted of (1→4)-β-D-Manp, (1→4)-β-D-Glcp, and (1→4)-α-D-Glcp residues. The anti-inflammatory efficacy and keratinocyte-protective potential of FDOPs (FDOP-1A and FDOP-2A) were investigated by using lipopolysaccharide (LPS)-induced RAW264.7 and HaCaT cells models, which showed significant inhibitions on the inflammatory factors of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and interleukin-1 beta (IL-1β); recovered levels of filaggrin (FLG), aquaporin 3 (AQP3), transient receptor potential vanilloid 4 (TRPV4), cathelicidin antimicrobial peptide (CAMP)/LL-37, and adiponectin (ADIPOQ); and the reduced protein expression of the TLR4/IκB-α/NF-κB/NLRP3 pathway. Notably, the FDOPs exhibited a remarkable reactive oxygen species (ROS) scavenging capacity, demonstrating superior antioxidant activity. Therefore, FDOPs show dual anti-inflammatory and antioxidant properties, making them suitable as active ingredients for modulating epidermal inflammation and promoting skin barrier repair. Full article

Andrographolide (AP), a bioactive compound from Andrographis paniculata, is known for its anti-inflammatory and antioxidant properties, both essential for wound healing. However, its effects on energy metabolism during tissue repair and its role in UVB-induced photoaging remain poorly understood. This study explored AP’s multitarget therapeutic effects on wound healing under photoaging conditions (PhA/WH) using network pharmacology and experimental validation. Scratch wound assays showed that AP promoted keratinocyte migration in UVB-exposed HaCaT cells. Bioinformatic analysis identified 10 key targets in PhA/WH, including TNF-α, IL-1β, JUN, PPARγ, MAPK3, TP53, TGFB1, HIF-1α, PTGS2, and CTNNB1. AP suppressed UVB-induced pro-inflammatory gene expression (IL-1β, IL-6, IL-8, and COX-2) and inhibited the phosphorylation of ERK1/2 and P38, while enhancing Hypoxia-Inducible Factor-1alpha (HIF-1α) and peroxisome proliferator-activated receptors (PPARγ) expression. GC/MS-based metabolomics revealed that AP reversed UVB-induced disruptions in fatty acid metabolism, glycolysis/gluconeogenesis, and tricarboxylic acid (TCA) cycle, indicating its role in restoring the metabolic balance necessary for tissue regeneration. In conclusion, andrographolide modulates key inflammatory and metabolic pathways involved in wound repair and photoaging. These mechanistic insights contribute to a better understanding of the molecular processes underlying skin regeneration under photodamage and may inform future therapeutic strategies. Full article

Distillers grains are the main by-products of the brewing industry, with a large output but a low degree of resource utilization. Exploring more efficient comprehensive utilization technologies for distillers grains is of great significance for increasing the added value of the brewing industry. This study took Moutai distillers grains as the research object, and the ultrasonic-assisted extraction process of crude flavonoids from distillers grains was first optimized. On this basis, the in vitro antioxidant and anti-inflammatory effects of the crude flavonoid extract were further explored. The results show that the optimal process parameters for ultrasonic-assisted extraction of crude flavonoids were an ethanol concentration of 95%, liquid-to-solid ratio of 26 mL/g, and ultrasonic time of 36 min (with a fixed ultrasonic power of 500 W). Under such conditions, the yield of crude flavonoid extract from Moutai distillers grains was 25.39% ± 5.05%. In vitro antioxidant results showed that 2 mg/mL of crude flavonoid extract had good DPPH and ABTS free radical scavenging activities (78.17% and 75.21%, respectively). In vitro anti-inflammatory results showed that 0.5% crude flavonoid extract (the survival rate of HaCaT cells treated with this concentration was greater than 80%) significantly reduced the secretion of the inflammatory factors IL-6 and IL-1β induced by TNF-α and IFN-γ. In summary, this study showed that Moutai distillers grains may provide easily accessible and inexpensive raw materials for the functional food and cosmetic industries. Full article

Atopic dermatitis (AD) is a common chronic skin disease affecting both children and adults. Currently lacking a clinical cure, AD presents significant physical and emotional challenges for patients and their families, substantially impacting their quality of life. This underscores significant unmet needs in AD management and highlights the necessity for developing effective therapeutic applications. Recently, several chlorine-containing active substances with promising pharmacological activity have been discovered in soft corals cultivated through coral farming. Among these, brianolide, isolated from the soft coral Briareum stechei, has shown promising potential. This study investigated brianolide’s regulatory effects on the inflammatory response in atopic dermatitis and its underlying mechanisms. Using an in vitro human keratinocyte cell line (HaCaT) stimulated with tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) to mimic AD inflammation, brianolide was found to inhibit cytokine and chemokine expression via the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB)-signaling pathways. In an in vivo animal model of 2,4-Dinitrochlorobenzene (DNCB)-induced AD, brianolide demonstrated anti-inflammatory effects, reducing transepidermal water loss (TEWL), ear thickness, erythema, and epidermal blood flow. These findings provide new insights into brianolide’s activity against AD-related inflammation, elucidate potential mechanisms, and contribute to understanding the pharmacological potential of natural coral products for AD treatment. Full article

Sinhyotaklisan (SHTLS) is a traditional herbal prescription composed of Lonicerae Flos, Angelicae Gigantis Radix, Astragali Radix, and Glycyrrhizae Radix et Rhizoma, commonly used to treat skin disorders. This study aimed to investigate the therapeutic effects and underlying mechanisms of SHTLS in psoriasis through the network pharmacology analysis and experimental validation in vitro and in vivo. Bioactive compounds and molecular targets were identified using the Traditional Chinese Medicine Systems Pharmacology database, and key protein–protein interaction networks were analyzed via STRING and Cytoscape. In vitro, HaCaT cells were pretreated with SHTLS and stimulated with TNF-α, followed by assessments using proliferation assays, scratch assays, quantitative real-time PCR, and Western blotting. In vivo, the anti-psoriatic effects of SHTLS were evaluated in an imiquimod-induced psoriatic mouse model. A total of 36 key targets were significantly enriched in TNF-α, MAPK, HIF-1α, and IL-17 signaling pathways. SHTLS suppressed TNF-α-induced expression of VEGF and HIF-1α, while upregulating p53, thereby inhibiting keratinocyte hyperproliferation and angiogenesis. It also reduced IL-6 and IL-8 levels and blocked activation of the NF-κB and MAPK pathways. Histological analysis confirmed that SHTLS alleviated psoriatic lesions in vivo. These findings suggest that SHTLS may be a promising therapeutic candidate for psoriasis by targeting hyperproliferation, angiogenesis, and inflammation. Full article

Ferroptosis, a regulated form of cell death driven by iron accumulation and lipid peroxidation, contributes to oxidative stress-related skin damage. This study evaluates the antioxidant and anti-inflammatory effects of a nanoformulation derived from an Annurca apple callus extract in an in vitro model of ferroptosis using human keratinocytes (HaCaT cells). A hydroalcoholic extract from light Annurca apple callus (LCE) was nanoformulated with Pluronic^® F127 and Soluplus^® to enhance stability and bioavailability. The resulting nanoformulation (NF-LCE) exhibited optimal particle size (103.17 ± 0.87 nm), polydispersity index (0.21 ± 0.00), and zeta potential (−1.88 ± 0.64 mV). Iron overload (100 µM) was employed to induce oxidative stress and inflammation in HaCaT cells, resulting in elevated levels of inflammatory markers (COX2, IL-6, TNF-α) and a diminished antioxidant response, as indicated by decreased expression of GPX4 and Nrf2. NF-LCE treatment restored GPX4 and Nrf2 levels (~0.8-fold increase, p < 0.05) while significantly reducing COX2 (36.6%, p < 0.01), IL-6 (79.6%, p < 0.0001), and TNF-α (30.9%, p < 0.1). These results suggest NF-LCE as a promising therapeutic strategy for mitigating ferroptosis-induced skin damage, warranting further investigation in advanced skin models and clinical applications. Full article

Psoriasis pathogenesis involves dysregulated immune responses, yet the role of protein prenylation (particularly PGGT1B-mediated geranylgeranylation) in macrophage-driven inflammation remains poorly understood. This study aims to explore the role and molecular mechanism of protein geranylgeranyltransferase type I subunit beta (PGGT1B) in the development of psoriasis. Myeloid cell-specific PGGT1B gene knockout mice were generated, and a mouse psoriasis model was established with imiquimod to study the role and mechanism of PGGT1B gene downregulation-induced macrophage activation in the pathogenesis of psoriasis. Bone marrow-derived macrophages (BMDMs) from wild-type and PGGT1B knockout mice were cultured and stimulated with resiquimod (R848) to simulate the immune microenvironment of psoriasis. In addition, the differentially expressed genes induced by PGGT1B knockout were analyzed using RNA-seq, and bioinformatics analysis was carried out to study the possible biological process of PGGT1B regulation. Finally, PMA-THP-1 was co-cultured with HaCaT cells to study the effect of PGGT1B deletion in macrophages on the proliferation and differentiation of keratinocytes. Bone marrow PGGT1B deficiency aggravated the psoriasis-like lesions induced by imiquimod in mice. In BMDMs with PGGT1B deficiency, the NF-κB signaling pathway was over-activated by R848, and the expressions of proinflammatory cytokines IL-1β, IL-6, and TNF-α were significantly increased. Activation of cell division cycle 42 (CDC42) may mediate the activation of the NF-κB pathway in PGGT1B-deficient BMDMs. PGGT1B deletion can promote the proliferation and inhibit the differentiation of HaCaT cells. Reduced PGGT1B levels can increase the expression of CDC42, which further activates NLRP3 inflammation in macrophages through NF-κB signaling, further aggravating the inflammatory state of psoriasis. Psoriasis-like lesions induced by IMQ are aggravated when PGGT1B expression is reduced in mouse bone marrow cells. A possible mechanism for this is that PGGT1B-deficient macrophages migrate to the epidermis more easily during psoriasis, which leads to the activation of Cdc42, NF-κB signaling, and NLRP3 inflammatory corpuscles. Full article

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. Full article

This study investigated the chemical composition and anti-inflammatory effects of essential oils extracted from Citrus aurantium flower, Citrus sinensis, Brazilian Citrus sinensis, Citrus limon, Citrus bergamia, and Citri Reticulatae Pericarpium using steam distillation and gas chromatography-mass spectrometry (GC-MS). Their anti-inflammatory activities were assessed in LPS-stimulated RAW 264.7 cells. Among them, Citri Reticulatae Pericarpium essential oil (CRPEO) exhibited the most potent anti-inflammatory effects, with D-Limonene (76.51%), α-Pinene (2.68%), and Linalool (2.11%) as its primary constituents. The CCK-8 assay showed that the essential oil exhibited no cytotoxicity on HaCaT cells at a concentration of 50 μg/mL. CRPEO significantly preserved cell viability and reduced the production of pro-inflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and nitric oxide (NO). Gene expression analysis via RT-qPCR further confirmed the downregulation of TNF-α, IL-6, IL-1β, and inducible nitric oxide synthase (iNOS) at the mRNA level. Network pharmacology and molecular docking studies were employed to identify α-Bulnesene as a key bioactive component of CRPEO and revealed that its principal target is the NLR Family Pyrin Domain-Containing 3 (NLRP3) inflammasome. These findings highlight the strong anti-inflammatory potential of CRPEO and suggest its promising therapeutic application for inflammation-related conditions. Full article

Background/Objective: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation products (LPOs). A chemotherapeutic drug, 5–fluorouracil (5–FU), can induce epithelial mucositis and favor drug synergism with erastin in ferroptosis. Camellia tea saponin extract (TS) is known to exert antioxidative properties. This study aims to delineate the protective role of TS in mitigating 5–FU-induced ferroptosis and inflammation in human keratinocytes. Methods: HaCaT cells were induced by 5–FU and erastin, treated with different TS doses, and their viability was then determined. Levels of cellular reactive oxygen species (ROS), LPOs, labile iron pool (LIP), glutathione (GSH), glutathione peroxidase 4 (GPX–4) activity, as well as IL–6, IL–1β, and TNF–α levels, and their wound healing properties were assessed. Results: TS per se (at up to 25 µg/mL) was not toxic to HaCaT cells but was unable to restore the viability of 5–FU-induced cells up to the baseline levels. The compound significantly diminished increases in cellular ROS, LPOs, and LIP, while restoring GSH content and GPX–4 activity. Additionally, it suppressed the cytokine production of 5–FU-induced cells in a concentration–dependent manner. Moreover, TS exerted wound-healing effects against skin injuries and 5–FU damage significantly and dose dependently. Conclusions: The insights of this work have identified biochemical mechanisms using tea saponin extract to protect against 5–FU-induced keratinocyte ferroptosis and inflammation. This study highlights the promising adjunctive potential of tea saponin in the mitigation and management of chemotherapy-induced mucositis. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by impaired barrier function and persistent inflammation, necessitating advanced therapeutic solutions. This study presents the development of a novel composite hydrogel scaffold composed of polyvinyl alcohol (PVA), gelatin, and Cnidium monnieri (CM) extract, designed to address the dual challenges of tissue regeneration and inflammation suppression. Fabricated via optimized freeze–thaw crosslinking and lyophilization, the scaffold exhibited a highly porous structure conducive to enhanced cell proliferation and controlled bioactive release. FT-IR analysis confirmed robust intermolecular interactions among PVA, gelatin, and CM bioactives, while SEM imaging revealed a well-developed porous network. The UPLC analysis demonstrated the sustained release of key CM compounds, such as osthole and imperatorin, which contributed to the scaffold’s anti-inflammatory properties. Biological assessments using HaCaT keratinocytes under inflammatory conditions induced by TNF-α and IFN-γ revealed improved cell viability and significant suppression of IL-8 expression, a critical marker in AD-related inflammation. These findings underscore the potential of the PVA/Gel/CM composite hydrogel as an advanced therapeutic platform for inflammatory skin disorders. Full article

The discovery of effective cysteine protease inhibitors with crude protein kiwi extracts (CPKEs) has created novel challenges and prospects for pharmaceutical development. Despite extensive research on CPKEs, limited research has been conducted on treating atopic dermatitis (AD). Therefore, the objective of this work was to investigate the anti-inflammatory effects of CPKEs on TNF-α activation in a HaCaT cell model and in a DNCB (1-chloro-2, 4-dinitrochlorobenzene)-induced atopic dermatitis animal model. The molecular weight of the CPKE was determined using SDS-PAGE under non-reducing (17 kDa and 22 kDa) and reducing conditions (25 kDa, 22 kDa, and 15 kDa), whereas gelatin zymography was performed to examine the CPKE’s inhibitory impact on cysteine protease (actinidin and papain) activity. Moreover, the CPKE remains stable at 60 °C, with pH levels varying from 4 to 11, as determined by the azocasein assay. CPKE treatment decreased the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, along with the activation of nuclear factor-kappa B (NF-κB)-p65 in tumor necrosis factor-α (TNF-α)-stimulated HaCaT cells. Five-week-old BALB/c mice were treated with DNCB to act as an AD-like animal model. The topical application of CPKE to DNCB-treated mice for three weeks substantially decreased clinical dermatitis severity and epidermal thickness and reduced eosinophil infiltration and mast cells into ear and skin tissues. These findings imply that CPKE derived from kiwifruit might be a promising therapy option for inflammatory skin diseases such as AD. Full article