Search Results (3,845)

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants—astaxanthin and Garcinia indica (kokum)—in modulating hepatic redox status, lysosomal function, and metabolic gene expression in a murine model of diet-induced NAFLD. A total of 120 male Swiss Webster mice were allocated into control and steatotic groups, followed by a 90-day supplementation period with astaxanthin, kokum, or their combination. Liver tissue was collected post-supplementation for biochemical, antioxidant, and qRT-PCR analyses. Outcomes included lysosomal enzymes activities, superoxide dismutase (SOD), GSH, vitamin C, total polyphenols, DPPH radical-scavenging activity, and total antioxidant capacity (TAC). NAFLD induced marked oxidative stress, lysosomal overactivation, and alteration of antioxidant-related gene expression. Combined supplementation restored GSH, enhanced TAC, reduced lysosomal stress markers, and significantly upregulated nuclear factor erythroid 2-related factor 2 (Nfe2l2) while downregulating fatty acid synthase (FASN) and partially rescuing lipoprotein lipase (LpL). Correlation analyses revealed strong associations between antioxidant capacity, lysosomal function, and transcriptional regulation, supporting the therapeutic relevance of combined antioxidant therapy for concurrent redox and lysosomal dysregulation in NAFLD. These findings underscore the therapeutic potential of targeting redox and cellular degradation pathways with antioxidant-based interventions to re-establish hepatic metabolic balance in NAFLD and related disorders. Full article

Ischemic stroke is a major cause of long-term disability and death, with oxidative stress contributing substantially to post-ischemic injury. Reperfusion restores oxygen supply but simultaneously increases reactive oxygen species (ROS), amplifying secondary neuronal damage. This study examined time-dependent changes in systemic thiol redox status following transient middle cerebral artery occlusion (tMCAO) in rats. Plasma concentrations of cysteine (CySH), cystine (CySS), glutathione (GSH), and glutathione disulfide (GSSG), along with corresponding CySS/CySH and GSSG/GSH ratios and redox potentials (Eh), were evaluated 24 and 48 h after occlusion. At 24 h, thiol concentrations and redox ratios showed no significant differences between sham and tMCAO groups. By 48 h, a marked oxidative shift emerged, characterized by reduced CySH, elevated GSSG, and significant increases in both CySS/CySH and GSSG/GSH ratios. Redox potentials also demonstrated substantial oxidation at this time point. These findings indicate that prolonged ischemia–reperfusion induces systemic oxidative stress, with plasma redox status serving as a sensitive indicator of reperfusion-related injury. The results underscore the plasma redox status as a potentially sensitive biomarker of reperfusion-induced oxidative injury and support the therapeutic value of targeting redox imbalance to mitigate oxidative damage following stroke. Full article

A key objective of the dairy industry is to balance genetic progress with reproductive efficiency. Ovum pick-up followed by in vitro embryo production (OPU-IVP) is a pivotal technology for accelerating genetic gain. However, the relationship between follicle size and oocyte developmental competence in high-producing dairy cows under hormonal stimulation remains to be fully elucidated. This study systematically evaluated the effects of follicle diameter ovum pick-up on OPU-IVP outcomes and the underlying follicular fluid (FF) microenvironment. A total of 109 high-yielding Holstein cows were subjected to ovarian stimulation and OPU. Follicles were categorized as small (2.0–5.9 mm), medium (6.0–9.9 mm), or large (10.0–20.0 mm). Oocyte recovery, quality, and developmental competence were assessed. FF was analyzed for hormonal profiles, including anti-Müllerian hormone (AMH), estradiol (E2), follicle-stimulating hormone (FSH), and progesterone (PROG); oxidative stress markers, including malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC); and untargeted metabolomics (n = 10 per group). Consistently, oocytes from medium follicles exhibited superior developmental competence, achieving the highest maturation (89.93%), cleavage (72.19%), and blastocyst rates (41.88%). In contrast, large follicles had a low recovery rate (32.64%), a high proportion of degenerated oocytes (32.00%), and reduced embryonic efficiency. Metabolomic profiling revealed distinct microenvironmental differences, with medium follicles enriched in pathways like pyruvate metabolism and arachidonic acid metabolism indicating an optimal metabolic state. Hormonally, AMH decreased while E2 and PROG increased with follicle size. Large follicles exhibited significantly elevated MDA levels, indicating oxidative stress, without a concurrent rise in antioxidant capacity. In conclusion, while small follicles provide an abundant source of morphologically good oocytes, medium follicles (6.0–9.9 mm) represent a distinct “window of competence” for OPU-IVP, characterized by a follicular microenvironment most conducive to embryo production. Excessive reliance on large follicle aspiration should be avoided due to signs of over-maturity and oxidative damage. These findings provide a physiological basis for optimizing OPU strategies to enhance IVP efficiency in high-producing dairy cows. Full article

Obesity is closely linked to dyslipidemia, hepatic injury, and chronic inflammation through disturbances in the gut–liver axis. Here, we evaluated the anti-obesity effects of L. rhamnosus (Lacticaseibacillus rhamnosus) CU262 in a high-fat diet (HFD) mouse model and elucidated mechanisms using an integrated multi-omics strategy. Male C57BL/6 mice received CU262 during 12 weeks of HFD feeding. Phenotypes, serum/liver biochemistry, gut microbiota (16S rRNA sequencing), fecal short-chain fatty acids (SCFAs), and hepatic transcriptomes (RNA-seq) were assessed. CU262 significantly attenuated weight gain and adiposity; improved serum TC, TG, LDL-C and HDL-C; lowered ALT/AST and FFA; and mitigated oxidative stress and inflammatory imbalance (↓ IL-6/TNF-α, ↑ IL-10). CU262 restored alpha diversity, reduced the Firmicutes/Bacteroidetes ratio, enriched beneficial taxa (e.g., Akkermansia), and increased acetate and butyrate. Liver transcriptomics showed CU262 reversed HFD-induced activation of cholesterol/steroid biosynthesis and endoplasmic reticulum stress, with downregulation of key genes (Mvk, Mvd, Fdps, Nsdhl, and Dhcr7) and Pcsk9, yielding negative enrichment of steroid and terpenoid backbone pathways and enhancement of oxidative phosphorylation and glutathione metabolism. Correlation analyses linked Akkermansia and SCFAs with improved lipid/inflammatory indices and repression of cholesterol-synthetic and stress-response genes. These findings demonstrate that CU262 alleviates HFD-induced metabolic derangements via microbiota-SCFA-hepatic gene network reprogramming along the gut–liver axis, supporting its potential as a functional probiotic for obesity management. Full article

This study aimed to evaluate the effects of an ethanolic extract from Punica granatum L. (EE-PG) on bovine ovarian tissue vitrification, focusing on follicular morphology, ultrastructure, stromal cell density, collagen distribution, redox status, and mRNA expression of antioxidant-related genes. Bovine ovarian cortex fragments were divided into a fresh control group for in vivo tissue evaluation or vitrified either with the base vitrification solution (αMEM) alone or supplemented with different concentrations of EE-PG (10, 50, and 100 µg/mL), and subsequently stored in liquid nitrogen for 5 days. After warming, fragments were allocated for morphological and oxidative stress analyses or incubated for 24 h to resumption of cellular metabolism. The concentrations of 10 and 100 µg/mL preserved follicular morphology immediately after warming, and were therefore selected for ultrastructural evaluation. Both concentrations mitigated vitrification-induced damage. Gene expression analysis showed decreased levels of catalase (cat), Glutathione Peroxidase 1 (gpx1), and Nuclear Factor Erythroid 2-Related Factor 2 (nrf2) compared with the fresh control, whereas Superoxide Dismutase (SOD) enzymatic activity increased after incubation with 10 µg/mL EE-PG compared with all experimental groups. Moreover, Malondialdehyde (MDA) levels in tissues treated with 10 or 100 µg/mL were comparable to fresh controls after incubation. Overall, EE-PG at 10 or 100 µg/mL in the vitrification solution supported the maintenance of tissue morphology, redox balance—despite the downregulation of essential antioxidant genes, which may be associated with a reduced demand for enzymatic antioxidant defense—and cellular metabolism, indicating potential for improving bovine ovarian tissue vitrification outcomes. Full article

Background and Objectives: This study aims to analyze the effects of levetiracetam (LEV) and valproic acid (VPA) administration on oxidative stress, inflammation, apoptosis, extracellular matrix dynamics, and bone remodeling parameters in rat alveolar bone exposed to orthodontic force. Materials and Methods: Four experimental groups were designed for this study: Control, Force, Force + LEV, and Force + VPA. LEV (150 mg/kg/day) or VPA (300 mg/kg/day) was administered intraperitoneally to the experimental groups daily for 6 weeks. At the end of the experimental period, the alveolar bone tissues were used for molecular analyses. RT-PCR analysis was performed to assess the expression levels of antioxidant markers [superoxide dismutase, (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH)], inflammatory cytokines [tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)], apoptosis-related genes (Bax, Bcl-2, and Caspase-3), matrix remodeling genes [matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and metallopeptidase inhibitor 1 (TIMP-1)], and bone metabolism regulators [receptor activator of nuclear factor kappa-Β ligand (RANKL) and osteoprotegerin (OPG)]. Oxidative stress and inflammatory measurements were also confirmed via ELISA assays. Results: The results demonstrated that orthodontic force application increased oxidative stress, inflammation, and apoptosis compared to the Control group, disrupted extracellular matrix homeostasis, and increased bone resorption, while LEV administration (LEV + Force) markedly mitigated these abnormalities. In other words, LEV administration increased levels of antioxidant markers, decreased levels of inflammatory cytokines and pro-apoptotic genes, restored extracellular matrix balance (decrease in MMP-2 and MMP-9 with concurrent upregulation of TIMP-1), and limited tissue destruction (decrease in RANKL along with elevation in OPG). In contrast to LEV, VPA did not correct these molecular alterations induced by orthodontic force and, in several parameters, further exacerbated them. Conclusions: In conclusion, molecular data from the animal model indicate that LEV plays a protective role against orthodontic force by reducing excess levels of oxidative stress, apoptosis, and inflammation and homeostatic pathways. Full article

In recent years, heavy metal emissions in Lhasa have been increasing, which has an impact on the local water environment. The negative effects of copper (Cu²⁺) on aquatic ecosystems have attracted much attention, as even low concentrations of Cu²⁺ can exert toxic effects on aquatic organisms. However, the impact of Cu²⁺ on native fish species from the Lhasa River remains poorly understood. In this study, Schizopygopsis younghusbandi (S. younghusbandi) larvae were exposed to Cu²⁺ at concentrations of 0. 5, 5, 50, and 500 μg/L for 7 or 14 days to evaluate its toxic effects on thyroid function and the antioxidant system. The results indicate that whole-body total thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased following Cu²⁺ exposure. This decrease was accompanied by a marked increase in dio1 and dio2 gene expression and decreased expression of thyroid hormone synthesis genes (nis, tg, ttf1 and pax8) after exposure to Cu²⁺. Furthermore, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) and the content of lipid peroxidation were increased, while the content of glutathione (GSH) was decreased. In addition, the survival rates and body lengths of S. younghusbandi larvae were significantly reduced following 7- and 14-day Cu²⁺ exposure. The Integrated Assessment of Biomarker Response (IBR) analysis further revealed dose- and time-dependent effects of Cu²⁺ on the larvae. In conclusion, the findings demonstrate that Cu²⁺ exposure induced disruption of thyroid endocrine and antioxidant systems and caused developmental toxicity in S. younghusbandi larvae. Full article

Type 2 diabetes mellitus (T2DM) involves chronic hyperglycemia, insulin resistance, low-grade inflammation, and oxidative stress that drive cardiometabolic and renal damage despite current therapies. Sodium–glucose cotransporter (SGLT) inhibitors have reshaped the treatment landscape, but residual risk and safety concerns highlight the need for new agents that combine glucose-lowering efficacy with redox–inflammatory modulation. LASSBio-1986 is a synthetic N-acylhydrazone (NAH) derivative designed as a gliflozin-like scaffold with the potential to interact with SGLT1/2 while also influencing oxidative and inflammatory pathways. Here, we integrated in silico and in vivo approaches to characterize LASSBio-1986 as a multifunctional antidiabetic lead in murine models of glucose dysregulation. PASS and target class prediction suggested a broad activity spectrum and highlighted transporter- and stress-related pathways. Molecular docking indicated high-affinity binding to both SGLT1 and SGLT2, with a modest energetic preference for SGLT2, and ADME/Tox predictions supported favorable oral drug-likeness. In vivo, intraperitoneal LASSBio-1986 improved oral glucose tolerance and reduced glycemic excursions in an acute glucose challenge model in C57BL/6 mice, while enhancing hepatic and skeletal muscle glycogen stores. In a dexamethasone-induced insulin-resistance model, LASSBio-1986 improved insulin sensitivity, favorably modulated serum lipids, attenuated thiobarbituric acid-reactive substances (TBARS), restored reduced glutathione (GSH) levels, and rebalanced pro- and anti-inflammatory cytokines in metabolic tissues, with efficacy broadly comparable to dapagliflozin. These convergent findings support LASSBio-1986 as a preclinical, multimodal lead that targets SGLT-dependent glucose handling while mitigating oxidative and inflammatory stress in models relevant to T2DM. Chronic disease models, formal toxicology, and pharmacokinetic studies, particularly with oral dosing, will be essential to define its translational potential. Full article

Plastic pollution is acknowledged as a serious problem for ecosystems. Among these plastics, polystyrene nanoplastics (PS-NPs) are emerging environmental pollutants, and their biological effects on hepatotoxicity are the least explored. Therefore, the present work examined the effect of PS-NPs on the hepatic transcription of the antioxidant genes Hmox1 and Sod3 in mice (n = 6, treatment (PS-NPs) vs. vehicle group (Veh)), mediated by RORγ and epigenetic modifications. The results show that PS-NP mice had significantly reduced body weight; increased activity of adenosine triphosphate (ATP), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH), and Complexes I, III, and V in the liver; and increased Alanine Transaminase (ALT), Aspartate Transaminase (ASP), Alkaline Phosphatase (ALP), malondialdehyde (MDA) and reactive oxygen species (ROS) compared to the Veh group. Furthermore, PS-NPs resulted in considerably lower relative mRNA expression of Hmox1, Sod3, and RORγ in the liver than the Veh group. Likewise, when compared to Veh, PS-NPs significantly reduced the enrichment of RORγ, as well as the occupancies of the key components of the transcriptional activation pathway (P300, SRC1, Pol II, Ser5-Pol II, and Ser2-Pol II) at the loci of Hmox1 and Sod3. In comparison to Veh, PS-NPs showed downregulated occupancies of the histone active marks H3K9ac and H3K18ac, while H3K4me3 and H3K27me3 were higher at the target loci of Hmox1 and Sod3. In conclusion, the present study highlights that PS-NPs induce oxidative stress by modifying Hmox1 and Sod3 in mice’s livers through histone changes and nuclear receptor RORγ modulation. Full article

Background/Objectives: Astrocytes are key regulators of brain energy homeostasis, integrating glucose metabolism with antioxidant support for neuronal function. Dysregulation of these processes contributes to neurodegenerative diseases, including Alzheimer’s disease. Andrographolide, a bioactive diterpenoid from Andrographis paniculata, has been reported to exert neuroprotective effects through the modulation of Wnt/β–catenin signaling and neuronal metabolism; however, its actions on astrocytic metabolic pathways remain insufficiently characterized. Methods: Here, we investigated the effects of andrographolide on metabolic and redox parameters in primary mouse cortical astrocytes. Results: Andrographolide increased glucose uptake and antioxidant capacity without affecting AMPK activation or the activity of core glycolytic enzymes. Instead, it selectively enhanced glucose-6-phosphate dehydrogenase activity, promoting glucose flux through the pentose phosphate pathway in a partially Wnt-dependent manner. This metabolic reprogramming was associated with increased NADPH availability and glutathione levels, together with a reduced ATP/ADP ratio, consistent with a shift toward redox maintenance rather than maximal energy production. Conclusions: Collectively, these findings highlight astrocytic metabolic plasticity as a relevant and underexplored target of andrographolide and support the concept that natural compounds can enhance brain resilience by modulating glial redox metabolism. Full article

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), poses a severe threat to global wheat production. The adaptor protein complex AP-1 plays a crucial role in vesicular trafficking, yet its function in rust fungi remains poorly understood. In this study, a gene encoding an AP-1 σ subunit, designated PsAP1, was identified in Pst. The expression of PsAP1 was highly induced during the early infection stage. Heterologous expression of PsAP1 in a Fusarium graminearum mutant partially restored its pathogenic defects. Subcellular localization analysis revealed that PsAP1 localizes to the plasma membrane, cytoplasm, and nucleus. Silencing PsAP1 in wheat using Barley stripe mosaic virus-mediated host-induced gene silencing (BSMV-HIGS) significantly attenuated Pst pathogenicity, reducing hyphal growth by 6.7% (colony diameter), sporulation by 61.6% (lesion length), and pathogen biomass by 66%, along with enhanced accumulation of host reactive oxygen species. Transcriptomic analysis further demonstrated that silencing PsAP1 disrupted multiple pathways, including MAPK signaling, glutathione metabolism, and carbohydrate metabolism. These findings indicate that PsAP1 facilitates Pst infection by modulating vesicular trafficking, suppressing host immunity, and reprogramming host metabolism. This study provides novel insights into the pathogenic mechanisms of rust fungi and suggests a potential target for disease control. Full article

With the growing prominence of skin photodamage caused by ultraviolet (UV) radiation, the development of efficient and safe natural photoprotectants has become a major research focus. Ginsenoside Re (G-Re), a primary active component of ginseng (Panax ginseng C. A. Mey.), has attracted much attention due to its significant antioxidant and anti-inflammatory activities; however, its systemic role and mechanism in protecting against photodamage remain unclear. In this study, a UVB-induced rat photodamage model was established to evaluate the protective effect of ginsenoside Re through histopathological staining, biochemical assay, and immunohistochemical analysis. Furthermore, an integrated transcriptomic and metabolomic approach was applied to elucidate the molecular mechanism of G-Re protection and to establish the association between the photodamage phenotype, metabolic pathways, and gene functions. Following their identification via integrated multi-omics analysis, the key targets were subjected to verification via Western blotting. The results showed that G-Re could effectively alleviate UVB-induced pathological injury and reduce the level of oxidative stress and inflammatory factors, which could reverse regulate the abnormal expression of 265 differential genes and 30 metabolites. The glutathione metabolism pathway was proven as a key pathway mediating the protective effects of ginsenoside Re against skin photodamage via integrated analysis, WB verification, and molecular docking. The current study indicated that G-Re could be a promising natural sunscreen additive in cosmetical products. Full article

Quercetin (Q), a bioactive flavonoid, exerts potent antioxidant and redox-modulating effects by activating the nuclear factor erythroid 2-related factor 2/antioxidant response Element (Nrf2/ARE) pathway and upregulating endogenous antioxidant defenses, including enzymatic antioxidants such as superoxide dismutase (SOD) and catalase (CAT), as well as non-enzymatic glutathione (GSH) and lipid peroxidation (MDA). Gemcitabine (Gem), a widely used antimetabolite chemotherapeutic, often shows limited efficacy under hypoxic and oxidative stress conditions driven by hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF)-mediated angiogenesis. This study investigated the redox-mediated synergistic effects of Q and Gem in MDA-MB-231 human breast cancer cells. Combination treatment significantly reduced cell viability beyond the expected Bliss value, indicating a synergistic interaction and enhanced apoptosis compared with single-agent treatments. Increased reactive oxygen species (ROS) production was accompanied by depletion of GSH and accumulation of MDA, establishing a pro-apoptotic oxidative stress environment. Q alone enhanced SOD and CAT activities, whereas the combination induced exhaustion of antioxidant defenses under oxidative load, reflecting a redox-adaptive response. Molecular analyses revealed downregulation of HIF-1α and VEGF, alongside upregulation of Bax and Caspase-3, confirming suppression of hypoxia-driven survival and activation of the intrinsic apoptotic pathway. Transcriptomic and enrichment analyses further identified modulation of oxidative stress- and apoptosis-related pathways, including phosphoinositide-3-kinase–protein kinase B/Akt (PI3K/Akt), HIF-1 and VEGF signaling. Collectively, these results indicate that Q potentiates Gem cytotoxicity via redox modulation, promoting controlled ROS elevation and apoptosis while suppressing hypoxia-induced survival mechanisms, highlighting the therapeutic potential of redox-based combination strategies against chemoresistant breast cancer. Full article

Background/Objectives: In all types of diabetes, elevated blood glucose levels cause pathological changes in skeletal muscle, primarily due to oxidative stress, mitochondrial dysfunction, and excessive production of reactive oxygen species (ROS). Regular exercise can help mitigate these effects; however, the underlying mechanisms, particularly those involving the mitochondrial permeability transition pore (mPTP), remain incompletely understood. This study aimed to explore the effects of aerobic exercise training (AET) on oxidative stress and the expression of mPTP components in the skeletal muscle of streptozotocin-induced diabetic rats. Methods: Male Wistar rats were randomly divided into three groups: Healthy Sedentary (H-SED), Diabetic Sedentary (D-SED), and Diabetic Exercise-trained (D-EXER); n = 6 per group. The D-EXER group performed AET (0° slope) 5 days/week for 8 weeks. After the intervention period, body weight and fasting blood glucose (FBG) levels were measured, and soleus muscles were collected and analyzed for oxidative stress biomarkers, Western blotting, and gene expression using qRT-PCR. Results: Following an 8-week intervention, AET reduced FBG concentrations. Accordingly, in the soleus muscles of the D-EXER group, ROS levels decreased, and redox balance was improved compared to the D-SED group. Exercise training reduced CypD and Casp9 mRNA expression and increased Bcl-2 mRNA expression, whereas Ant1 mRNA expression was only slightly altered. CypD protein expression was decreased in exercised diabetic rats, while VDAC1 protein and mRNA levels remained unchanged. In the D-EXER group, there were significant inverse correlations between CypD and Casp9 mRNA expression levels and glutathione redox state. Conclusions: The current study suggests that 8 weeks of AET, in addition to reducing hyperglycemia, may favorably influence oxidative balance and the expression of mPTP-related molecular components in diabetic skeletal muscle. Full article

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease often causing functional disability. Current therapies provide only temporary relief and can cause adverse effects that frequently result in pain and disability. Current pharmacological options offer only temporary symptom relief and may cause adverse effects. Piper sarmentosum (PS), a plant traditionally used for its medicinal properties, has demonstrated antioxidant and anti-inflammatory activities that may counteract OA-related degeneration. This study provides preliminary insight into the therapeutic potential of PS aqueous extract in human OA chondrocytes. Methods: Compounds in the PS aqueous extract were profiled using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Primary human OA chondrocytes (HOCs) were treated with 0.5, 2, and 4 µg/mL of PS aqueous extract for 72 h. Key OA-related parameters were assessed, including anabolic markers (sulfated glycosaminoglycan (sGAG), collagen type II (COL II), aggrecan core protein (ACP), SRY-box transcription factor 9 (SOX9)), catabolic markers (matrix metalloproteinase (MMP) 1, MMP13, cyclooxygenase 2 (COX2)), oxidative stress (nitric oxide (NO) production, inducible NO synthase (iNOS) expression), and inflammatory responses (interleukin (IL) 6). Gene expression was quantified using qPCR, and protein levels were evaluated using the colorimetric method, immunocytochemistry, and Western blot. Results: A total of 101 compounds were identified in the extract, including vitexin, pterostilbene, and glutathione—bioactives known for antioxidant, anti-inflammatory, and chondroprotective functions. PS-treated chondrocytes maintain healthy polygonal morphology. PS aqueous extract significantly enhanced anabolic gene expression (COL2A1, ACP, SOX9) and sGAG production, while concurrently suppressing COX2 expression and NO synthesis. Additionally, PS aqueous extract reduced COX2 and iNOS protein levels, indicating inhibition of the NO signaling pathway. Catabolic activity was attenuated, and inflammatory responses were partially reduced. Conclusions: PS aqueous extract exhibits promising chondroprotective, antioxidant, and anti-inflammatory effects in human OA chondrocytes, largely through the suppression of NO-mediated catabolic signaling. The presence of multiple bioactive compounds supports its mechanistic potential. These findings highlight PS aqueous extract as a potential therapeutic candidate for OA management. Further ex vivo and in vivo studies are warranted to validate its efficacy and clarify its mechanism in joint-tissue environments. Full article