Search Results (90)

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by extracellular matrix (ECM) breakdown, inflammation, and pain-associated functional impairment. Current pharmacological treatments primarily provide symptomatic relief without preventing cartilage degeneration. Kaempferia parviflora extract (KPE), rich in polymethoxyflavonoids, has been reported to have anti-inflammatory properties; however, its in vivo effects on cartilage homeostasis in OA remain incompletely defined. Methods: A monosodium iodoacetate (MIA)–induced rat model of knee OA was used to evaluate the therapeutic effects of KPE. Following OA induction, rats received oral KPE at low, medium, or high doses for 19 days. Pain-associated functional impairment was assessed by static weight-bearing analysis. Cartilage integrity was evaluated histologically, serum inflammatory and cartilage degradation biomarkers were quantified, and expression of matrix-degrading enzymes and their endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), was analyzed in articular cartilage. Results: MIA injection induced marked joint dysfunction, including an approximately 50% reduction in weight bearing on the affected limb. While KPE did not significantly reduce acute knee swelling, all KPE doses significantly improved weight-bearing imbalance compared with MIA controls. Histological analysis demonstrated preservation of cartilage structure and proteoglycan content in KPE-treated groups. Serum CTX-II levels were significantly reduced across all KPE doses, indicating attenuation of collagen degradation. Systemic inflammatory markers showed differential modulation: significant reductions in serum CRP and COX-2 at medium and high doses, while PGE2 showed a consistent downward trend that did not reach statistical significance. In articular cartilage, KPE treatment restored TIMP-1 expression, whereas modulation of individual MMPs was modest and variable. Conclusions: KPE alleviates OA-associated functional impairment and cartilage degeneration in an experimental OA model. The therapeutic effects are associated with reinforcement of TIMP-1–mediated matrix homeostasis and modulation of inflammatory pathways, supporting the potential of KPE as a natural adjunct candidate for OA management. Full article

Background: Tendinopathy remains a prevalent musculoskeletal disorder with limited disease-modifying pharmacotherapy. This study aimed to identify a reparative agent from the traditional medicinal herb Eucommiae Cortex and elucidate its mechanism of action. Methods: A bioactive fraction was first identified through a bioactivity-guided strategy using tenocyte cytoprotection and migration assays, then characterized by UHPLC-HRMS/MS. Its major constituent, aucubin (AU), which mirrors the fraction’s key pharmacological activities, was evaluated both in vitro and in vivo. In H₂O₂-injured tenocytes, AU’s effects on viability, apoptosis, oxidative stress (ROS, MDA, SOD) and inflammation (IL-1β, TNF-α) were assessed, with specific focus on estrogen receptor (ER) pathway involvement using pharmacological tools (17β-estradiol and (R, R)-THC). In a collagenase-induced Achilles tendinopathy model using male SD rats, AU’s therapeutic efficacy was evaluated via multimodal assessment: ultrasonography, histopathology (H&E, Masson’s trichrome, Sirius red), TEM, immunohistochemistry, and biochemical analysis of tissue markers. Results: AU effectively attenuated H₂O₂-induced tenocyte injury by enhancing viability, reducing apoptosis, and mitigating oxidative/inflammatory stress. These effects were mimicked by 17β-estradiol and reversed by the selective ERβ antagonist (R, R)-THC, indicating ERβ dependence. In vivo, AU treatment promoted structural and functional recovery, improved collagen maturity (increased Col I/Col III ratio and fibril diameter), suppressed matrix degradation (MMP-3, MMP-13) and apoptosis, and reduced oxidative stress and inflammation in tendon tissue. Conclusions: This study identifies aucubin as a novel phytoestrogenic compound from Eucommiae Cortex that promotes tendon repair through an ERβ-mediated mechanism. These findings position ERβ activation as a promising therapeutic strategy for tendinopathy and highlight AU as a promising lead compound for further development. Full article

Skin aging arises from extracellular matrix degradation, inflammation, and pigmentation dysregulation, yet most existing rejuvenation strategies target only a subset of these processes. This study investigated the multimodal rejuvenation potential of a dual hyaluronic acid compound (DHC), composed of low- and high-molecular-weight HA integrated within a minimally cross-linked hybrid complex. In vitro assays using dermal fibroblasts, melanoma cells, and macrophages demonstrated that DHC enhanced fibroblast viability, collagen I/III and elastin production, antioxidant enzyme activity, and wound-healing capacity while reducing senescence markers. DHC markedly suppressed melanogenesis by downregulating the gene expression of MITF, TYR, and TRP1, and exerted strong anti-inflammatory activity by decreasing nitric oxide (NO) production and key cytokines, including TNF-α, IL-1β, IL-6, and CCL1. In a UVB-induced photoaging rat model, DHC reduced wrinkle depth, epidermal thickening, and melanin accumulation while improving elasticity, collagen density, hydration, and barrier integrity. Across these outcomes, DHC demonstrated biological effects that were comparable to, and in selected endpoints greater than, those of commonly used biostimulators and HA fillers in preclinical models. Collectively, these laboratory findings suggest that DHC exhibits broad preclinical bioactivity through combined biostimulatory, antioxidant, anti-inflammatory, and pigmentation-modulating effects. Further mechanistic and clinical studies are required to determine its translational relevance. Full article

Background/Objectives: Osteoarthritis (OA) is a pervasive chronic joint disease characterized by the triad of persistent articular cartilage degeneration, debilitating synovial inflammation, and sustained chronic pain. Although salmon nasal cartilage proteoglycan (SPG) is recognized for supporting joint health, the precise molecular mechanism underlying its effects during OA progression remains to be fully elucidated. This study evaluated the therapeutic efficacy of SPG using a monosodium iodoacetate (MIA)-induced mouse model. Methods: A total of 180 male C57BL/6J mice (six-week-old) were utilized, organized into three independent cohorts to analyze distinct analytical endpoints: (1) pain assessment, histology, and immunohistochemistry; (2) mRNA expression analysis for early-stage OA (Day 3); and (3) mRNA expression analysis for the late-stage OA (Day 28). All subjects received daily oral treatment via gavage, commencing 5 days prior to OA induction and continuing until the designated experimental termination points (either Day 3 or Day 28). Each cohort comprised five experimental groups (n = 10–12 per group): a saline-injected Sham group, an MIA-induced Control group, a positive comparator receiving celecoxib (CLX, 20 mg/kg/day), and two groups administered SPG at a dose of 50 or 100 mg/kg/day. Results: Our findings demonstrated that SPG, particularly at the 100 mg/kg dose, significantly mitigated joint pain symptoms, performing comparably to CLX. Histopathological assessments confirmed that SPG effectively preserved the structural integrity of the cartilage matrix and substantially reduced pathological damage, as evidenced by lower Mankin scores. Mechanistically, SPG treatment led to a marked downregulation of degradative enzymes, including matrix metalloproteinase-3 (MMP-3) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), while concurrently normalizing the levels of tissue inhibitors of metalloproteinases (TIMPs). Furthermore, SPG prevented the aberrant, over-compensatory expression of anabolic markers such as SRY-box transcription factor 9 (SOX-9), type II collagen alpha 1 chain (COL2A1), and aggrecan (ACAN) typically observed in the disease’s later stages. While SPG demonstrated a limited impact on broadly pro-inflammatory cytokine profiles, it specifically and significantly reduced interleukin-6 (IL-6) gene expression during the chronic phase. Conclusions: These results suggest that SPG serves as a promising natural agent that maintains articular homeostasis by balancing matrix metabolic pathways, positioning it as a scientifically validated functional food candidate for the management of joint health. Full article

Osteoarthritis (OA) is a debilitating joint disease affecting over 500 million people globally, characterized by cartilage degradation, chronic pain, and failed tissue repair. Neurogenic inflammation, driven by neuropeptides including Substance P (SP) and calcitonin gene-related peptide (CGRP), plays a key role in the pathogenesis of OA. This study explores the therapeutic potential of extracellular vesicles (EVs) derived from infrapatellar fat pad mesenchymal stem/stromal cells (IFP-MSCs) transduced with CGRP antagonist CGRP_8-37 (aCGRP IFP-MSC EVs). These EVs are enriched in anti-inflammatory miRNAs and proteins, and they express neprilysin (CD10), enabling SP degradation. Herein, several LncRNAs were identified, which have been known to interact with miRNAs that affect the knee joint homeostasis. Specifically, 11 LncRNAs (ZFAS1, EMX2OS, HOTAIRM1, RPS6KA2-AS1, DANCR, LINC-ROR, GACAT1, GNAS-AS1, HAR1A, OIP5-AS1, TERC) interact with miRNAs that promote cell proliferation, prevent apoptosis, and preserve homeostasis. In vitro, aCGRP IFP-MSC EVs downregulated pro-inflammatory markers (TNF, TLR4, MAPK8) in dorsal root ganglia and promoted chondrocyte gene expression consistent with anabolism and matrix remodeling. In vivo, intra-articular EV delivery attenuated pain behaviors, preserved the cartilage structure, restored PRG4+ stem/progenitor cell localization, and trended toward reduced SP levels. Histological analysis confirmed improved collagen organization and reduced matrix degradation. These findings suggest that aCGRP IFP-MSC EVs exert multimodal effects on neuroinflammation, cartilage regeneration, and joint homeostasis. This cell-free, gene-enhanced EV therapy offers a promising disease-modifying strategy for the treatment of OA, with the potential to address both structural changes and chronic pain associated with this disease. Full article

Background: Photoaging, induced by chronic ultraviolet (UV) exposure, is a multifactorial skin disorder characterized by oxidative stress, inflammation, and extracellular matrix degradation. Ganoderma lucidum glycoprotein (Gl-Gp) exhibits potent antioxidant activity, but its topical application is limited by poor transdermal permeability. This study aimed to develop a microemulsion-based system to enhance Gl-Gp delivery and evaluate its anti-photoaging efficacy. Methods: Gl-Gp was extracted and purified from G. lucidum fruiting bodies and structurally characterized for O-glycosidic linkages and O-GlcNAc modifications. Fourier-transform infrared (FT-IR) spectroscopy further confirmed the polysaccharide–protein complex structure of Gl-Gp. A water-in-oil Gl-Gp microemulsion was prepared and assessed in vitro for antioxidant and cytoprotective effects in HaCaT cells, including reactive oxygen species (ROS) reduction, mitochondrial membrane potential stabilization, and apoptosis inhibition. Transdermal penetration was compared with aqueous Gl-Gp. In vivo efficacy was evaluated in a UV-induced rat model by measuring skin morphology, histology, oxidative stress markers, matrix metalloproteinases, and proinflammatory cytokines. Results: The microemulsion enhanced Gl-Gp stability and transdermal delivery. In vitro, it reduced ROS, preserved mitochondrial function, and decreased apoptosis in HaCaT cells. In rats, topical application attenuated erythema and epidermal hyperplasia, promoted dermal restoration, increased SOD and GSH-Px activities, and decreased MDA, hydroxyproline, MMPs, and inflammatory mediators. Conclusions: The Gl-Gp microemulsion exerts antioxidant, anti-inflammatory, and anti-collagen-degrading effects, representing a promising strategy for transdermal delivery and topical prevention of photoaging. Full article

Background/Objectives: Particulate matter (PM), which comprises airborne pollutants characterized by small sizes (typically from 5 to 8 μm in Korea), adversely affect skin health and accelerate aging by inducing oxidative stress and upregulating the expression of matrix metalloproteinase-1 (MMP-1), an enzyme responsible for collagen degradation. The skin, which is the largest organ and the primary barrier against harmful external stimuli such as air pollution, is particularly vulnerable to continuous PM exposure, which can cause skin aging and carcinogenesis. Given the effects of PM on skin aging, identifying compounds that can mitigate these adverse effects is crucial. Genistein is a naturally occurring isoflavone that has not been extensively studied in the context of PM-induced skin aging. Methods: In this study, we investigated the protective effects of genistein against PM-induced skin aging in HaCaT human keratinocytes. Results: Our results demonstrated that genistein treatment significantly reduced PM-induced MMP-1 expression, indicating a protective effect against collagen degradation. Additionally, genistein decreased the expression of the transcription factors activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB), both of which are involved in the regulation of MMP-1. Furthermore, genistein markedly reduced the production of reactive oxygen species (ROS), a key marker of oxidative stress induced by PM exposure. Conclusions: These findings suggest that genistein exerts protective effects against PM-induced skin aging by attenuating collagen degradation and oxidative stress, indicating its potential as a therapeutic agent for improving skin aging associated with PM exposure. Full article

Oxidative stress and chronic inflammation are major contributors to skin aging, promoting collagen degradation and impairing dermal structure. These factors stimulate the expression of matrix metalloproteinases, accelerating collagen breakdown and leading to wrinkles, sagging, and loss of elasticity. Given the key role of collagen in maintaining skin firmness and integrity, strategies that enhance collagen synthesis are essential for anti-aging interventions. This study investigated the combined effects of Yeast/Rice Fermentation Filtrate (RFF) and sialic acid (SA) on collagen production, antioxidation, and anti-inflammation, as well as their underlying mechanisms. The combination of RFF and SA significantly increased collagen genes transcription and mRNA stability, thereby enhancing collagen accumulation in the extracellular matrix. RNA-seq analysis revealed that RFF and SA modulate genes involved in the IL-17 signaling pathway. Mechanistically, RFF enhanced collagen mRNA stability by regulating HuR, while SA promoted collagen gene transcription via the TGF-β/Smad pathway. Moreover, the combination reduced the expression of inflammatory markers (IL-1β, IL-6, IL-8, PGE2, and NO) and improved cellular resistance to oxidative and inflammatory stress. These findings support the application of RFF and SA in anti-aging cosmetics and propose a novel strategy to enhance collagen production by simultaneously upregulating gene expression and stabilizing collagen mRNA. Full article

Background: Cutaneous aging is a multifactorial process, increasingly understood through the lens of cellular senescence, a state of stable cell cycle arrest accompanied by a pro-inflammatory secretory phenotype that disrupts tissue homeostasis. Recent research has highlighted the accumulation of senescent dermal fibroblasts as a key contributor to age-related skin changes, including loss of elasticity, collagen degradation, and impaired regeneration. Objective: This review explores the emerging hypothesis that energy-based devices (EBDs), particularly lasers, may act as senotherapeutic tools by targeting cellular senescence pathways in aging skin. We examine the molecular and histological effects of laser therapy in relation to known biomarkers of senescence and evaluate their potential role in regenerative dermatology. Methods: We conducted a review of published studies on fractional lasers, red-light therapies, and other EBDs, focusing on their impact on fibroblast activity, extracellular matrix remodeling, and senescence-associated markers such as p16^INK4a, p21^Cip1, telomerase, and SASP-related cytokines. Comparative analysis with pharmacologic senotherapeutics was also performed. Results: Preclinical and clinical data suggest that specific EBDs can modulate dermal aging at the molecular level by enhancing mitochondrial activity, increasing type III collagen synthesis, reducing senescence-related gene expression, and promoting fibroblast turnover. In contrast to systemic senolytics, lasers provide localized and titratable interventions with a favorable safety profile. Conclusions: Energy-based devices, particularly fractional lasers and red-light systems, hold promise as non-invasive senotherapeutic interventions in dermatology. By modulating senescence-associated pathways, EBDs may offer not only cosmetic improvement but also biological rejuvenation. Further mechanistic studies and biomarker-based trials are warranted to validate this paradigm and refine treatment protocols for longevity-oriented skin therapies. Full article

Background and Objectives: Osteoarthritis (OA) is a degenerative joint disease involving inflammation, oxidative stress, and extracellular matrix (ECM) degradation, leading to cartilage damage and joint dysfunction. This study aimed to evaluate the chondroprotective effects of intra-articular hydrolyzed collagen in a rat model of knee OA using a dual-compartment biochemical and histological approach. Materials and Methods: Twenty male Sprague-Dawley rats underwent ACL transection to induce osteoarthritis and were randomly assigned to receive intra-articular hydrolyzed collagen or saline once weekly for three weeks. At six weeks, knee joints were evaluated histologically using the Mankin score. Synovial fluid and cartilage homogenates were analyzed via enzyme-linked immunosorbent assay (ELISA) for cytokines, cartilage degradation markers, and oxidative stress indicators. Results: The collagen-treated group demonstrated significantly lower Mankin scores. Levels of pro-inflammatory cytokines, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), as well as cartilage degradation markers, matrix metalloproteinase-13 (MMP-13), C-terminal crosslinked telopeptide of type II collagen (CTX-II), and cartilage oligomeric matrix protein (COMP), were significantly reduced (p < 0.05). Additionally, oxidative stress indicators including inducible nitric oxide synthase (iNOS), total oxidant status (TOS), and oxidative stress index (OSI) were decreased, while total antioxidant status (TAS) was increased in both synovial fluid and cartilage homogenates (p < 0.05). Conclusions: Intra-articular hydrolyzed collagen reduced inflammation, oxidative stress, and extracellular matrix (ECM) degradation, indicating potential chondroprotective effects across both synovial and cartilage compartments. Full article

Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article

Skin ageing is a complex biological process influenced by cellular senescence, oxidative stress, and extracellular matrix degradation. Emerging evidence suggests that plant-derived bioactive compounds and extracellular vesicles (EVs) play a crucial role in modulating cellular homeostasis, promoting tissue regeneration, and counteracting age-related morphological and functional changes. This study investigates the impact of Haberlea rhodopensis in vitro culture extracts, native and enriched with EVs, on key cellular processes, including morphology, mitochondrial dynamics, lysosomal activity, gene expression, and genotoxicity in human dermal fibroblasts. The extracellular vesicles were identified in terms of shape, size, and morphology using dynamic light scattering, negative staining and observation under a transmission electron microscope. A comprehensive in vitro analysis was conducted utilizing light microscopy to assess cellular morphology and lysosomal mass, fluorescence microscopy for actin cytoskeletal organization, mitochondrial integrity, and nuclear morphology, and gene expression profiling for markers associated with collagen synthesis (COL1A1, COL3A1), senescence (CDKN1A), and oxidative stress response (NFE2L2). Additionally, cell cycle progression was evaluated, and genotoxicity was assessed using the neutral comet assay. Haberlea rhodopensis in vitro culture extracts and EVs were found to preserve fibroblast morphology, enhance mitochondrial mass, and upregulate collagen-related gene expression. These effects were concentration-dependent. The extracts exhibited biocompatibility with minimal genotoxic effects, indicating their potential as safe bioactive agents for skin rejuvenation. The findings suggest that Haberlea rhodopensis in vitro culture extracts and their enrichment with extracellular vesicles hold promise for cosmetic and dermatological applications, particularly in enhancing collagen production, preserving cellular integrity, and mitigating age-related alterations in skin fibroblasts. Further studies are warranted to elucidate the underlying molecular mechanisms and optimize formulation strategies for clinical translation. Full article

We investigated the effects of belt electrode-skeletal muscle electrical stimulation (B-SES) on muscle atrophy in collagen-induced arthritis (CIA) rats. Twenty-eight 8-week-old male Dark Agouti rats were immunized with type II collagen and Freund’s incomplete adjuvant (day 0). From days 14 to 28, 18 rats received B-SES (50 Hz) four times only on the right hindlimb (STIM), while the contralateral left hindlimb remained unstimulated. Both hindlimbs of 10 untreated CIA rats were defined as controls (CONT). Paw volume was measured every other day. On day 28, the muscle weight, histology, and gene expression of the soleus and extensor digitorum longus (EDL) were analyzed. B-SES did not worsen paw volume throughout the experimental period. Compared with CONT, the muscle weight and fiber cross-sectional area of the soleus were higher in STIM. The expression of muscle degradation markers (atrogin-1 and MuRF-1) in the soleus and EDL was lower in the STIM group than that in the CONT group. In contrast, B-SES did not significantly affect the expression of muscle synthesis (Eif4e and p70S6K) and mitochondrial (PGC-1α) markers. B-SES prevents muscle atrophy in CIA rats by reducing muscle degradation without exacerbating arthritis, demonstrating its promising potential as an intervention for RA-induced muscle atrophy. Full article

The biomechanical properties of the extracellular matrix (ECM) including its stiffness, viscoelasticity, collagen architecture, and temperature constitute critical biomechanical cues governing breast cancer progression. Matrix metalloproteinase 13 (MMP13) is an important marker of breast cancer and plays important roles in matrix remodelling and cell metastasis. Emerging evidence highlights MMP13 as a dynamic modulator of the ECM’s physical characteristics through dual mechanoregulatory mechanisms. While MMP13-mediated collagen degradation facilitates microenvironmental softening, thus promoting tumour cell invasion, paradoxically, its crosstalk with cancer-associated fibroblasts (CAFs) and tumour-associated macrophages (TAMs) drives pathological stromal stiffening via aberrant matrix deposition and crosslinking. This biomechanical duality is amplified through feedforward loops with an epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) populations, mediated by signalling axes such as TGF-β/Runx2. Intriguingly, MMP13 exhibits context-dependent mechanomodulatory effects, demonstrating anti-fibrotic activity and inhibiting the metastasis of breast cancer. At the same time, angiogenesis and increased metabolism are important mechanisms through which MMP13 promotes a temperature increase in breast cancer. Targeting the spatiotemporal regulation of MMP13’s mechanobiological functions may offer novel therapeutic strategies for disrupting the tumour–stroma vicious cycle. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, immune dysregulation, and vascular dysfunction, yet its pathogenesis remains incompletely understood. This study compares two widely used animal models of SSc—the bleomycin-induced fibrosis model and the collagen-V-induced autoimmune model—to evaluate their ability to replicate key disease features. In the bleomycin model, consistent cardiac fibrosis was observed across treatment groups despite variability in fibrosis in the skin and lungs, suggesting organ-specific differences in susceptibility. The collagen-V model demonstrated robust autoantibody production against collagen-V, confirming its utility in studying immune activation, though fibrosis was largely confined to the heart. While the bleomycin model excels at mimicking rapid fibrosis and is suitable for testing antifibrotic therapies, the collagen-V model provides insights into antigen-specific autoimmunity. Both models highlight the dynamic nature of fibrosis, where ECM deposition and degradation occur concurrently, complicating its use as a quantitative disease marker. Cardiac fibrosis emerged as a consistent feature in both models, emphasizing its relevance in SSc pathophysiology. Combining these models or refining their design through hybrid approaches, extended timelines, or sex and age adjustments could enhance their translational utility. These findings advance understanding of SSc mechanisms and inform therapeutic development for this challenging disease. Full article