Search Results (292)

Reactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-κB, STAT3, and HIF-1α. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology. Full article

Background/Objectives: Hair loss, driven by disrupted hair cycles, age-related hormonal imbalances, and oxidative stress, poses significant psychological challenges, necessitating the development of safe and effective therapies. This research investigates the trichogenic potential and underlying mechanisms of a standardized Ageratum conyzoides extract (ACE) using human follicle dermal papilla cells (HFDPCs) and C57BL/6 mice as models. Methods: HFDPCs were treated with ACE to assess its effects on 5α-reductase activity, estrogen receptor (ERα/ERβ) signaling, and activation of Wnt/β-catenin and MAPK pathways. Reactive oxygen species (ROS) levels and antioxidant enzyme expression were also evaluated. In vivo, C57BL/6 mice were administered ACE orally, and hair regrowth, follicle number and depth, and histological changes were measured. Results: In HFDPCs, ACE inhibited 5α-reductase activity, modulated ERα and ERβ signaling, and activated Wnt/β-catenin and MAPK pathways. ACE treatment at 100 μg/mL significantly increased β-catenin, p-GSK3β, and vascular endothelial growth factor (VEGF) expression (p < 0.01) and decreased Dickkopf-related protein-1 (DKK-)1 expression (p < 0.05). It also upregulated VEGF and other hair-growth-related factors and exhibited substantial antioxidant properties by reducing reactive oxygen species (ROS) and elevating the expression of antioxidant enzymes, notably SOD2 at 100 μg/mL. In C57BL/6 mice, oral administration of ACE significantly increased hair regrowth, with the 50 mg/kg group showing the most prominent effects, including increased hair follicle number and depth compared to the negative control group (p < 0.05). These effects were observed to be dose-dependent and comparable to those of minoxidil. Histological analysis confirmed enhanced anagen-phase follicle development. Conclusions: These findings highlight ACE’s multifaceted biological activity in promoting hair growth through hormonal modulation, pathway activation, and antioxidant protection, positioning it as a promising natural supplement for hair growth and health, although further clinical studies are required to confirm its efficacy in humans. Full article

HMG-CoA reductase inhibitors, statins, are extensively used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic disorders. However, one of the common side effects of statin therapy is a mild elevation in liver aminotransferases, observed in less than 3% of patients. Atorvastatin and simvastatin, in particular, are most frequently associated with statin-induced liver injury, leading to treatment discontinuation. Recent research has highlighted the antioxidant and anti-inflammatory properties of glucagon-like peptide-1 receptor (GLP-1R) activation in protecting against liver injury. Nonetheless, the potential protective effects of liraglutide (LIRA), a GLP-1R agonist, against atorvastatin (ATO)-induced liver dysfunction have not been fully elucidated. In this context, the present study aimed to investigate the protective role of LIRA in mitigating ATO-induced liver injury in rats, offering new insights into managing statin-associated hepatotoxicity. Indeed, LIRA treatment improved liver function enzymes and attenuated histopathological alterations. LIRA treatment enhanced antioxidant defenses by increasing Nrf2 content and superoxide dismutase (SOD) activity, while reducing NADPH oxidase. Additionally, LIRA suppressed inflammation by downregulating the HMGB1/TLR-4/RAGE axis and inhibiting the protein expression of pY323-MAPK p38 and pS635-NFκB p65 content resulting in decreased proinflammatory cytokines (TNF-α and IL-1β). Furthermore, LIRA upregulated GLP-1R gene expression and promoted autophagic influx via the activation of the pS473-Akt/pS486-AMPK/pS758-ULK1/Beclin-1 signaling cascade, along with inhibiting apoptosis by reducing caspase-3 content. In conclusion, LIRA attenuated ATO-induced oxidative stress and inflammation via activation of the Nrf-2/SOD cascade and inhibition of the HMGB1/TLR-4/RAGE /MAPK p38/NFκB p65 axis. In parallel, LIRA stimulated autophagy via the AMPK/ULK1/Beclin-1 axis and suppressed apoptosis, thus restoring the balance between autophagy and apoptosis. Full article

Inflammation, oxidative stress, and androgen activity are key features in benign prostate hyperplasia (BPH). Risks associated with the long-term use of 5α-reductase inhibitors have led to the search for alternative therapies, including food supplements. This study investigates the effectiveness of the combination of pollen extracts, namely Graminex^®G96^® (G) and Teupol 25P (T), towards oxidative stress and inflammation on human macrophages and benign prostate hyperplasia cells (BPH-1), both of which are LPS stimulated. The Nrf2-dependent antioxidant intracellular cascade as well as the NF-ĸB-driven inflammatory cascades were analyzed. The anti-proliferative effect of G and T, alone and in association, were evaluated on prostatic adenocarcinoma cells (PC-3) and BPH-1 cells. Finally, the inhibitory activity of GT on 5α-reductase was investigated in PC-3 cells by measuring epiandrosterone amounts, with the 5α-reductase inhibitor finasteride administered for comparison. All experiments were conducted in triplicate; data are presented as mean values ± standard deviations. Statistical analysis was performed using one-way analysis of variance. Our work demonstrates that GT promotes Nrf2-dependent antioxidant responses and counteracts the NF-ĸB-driven pathway in macrophages. GT is effective in counteracting the expression of pro-inflammatory cytokines and the generation of reactive oxygen species by promoting HO-1-dependent antioxidant responses in BPH-1 cells. GT reduces PC-3 and BPH-1 proliferation when associated with finasteride through a statistically significant inhibition of 5α-reductase activity. Data obtained in vitro and in silico demonstrate the potential efficacy of a multitargeted approach in the treatment of BPH. Full article

CD38, a nicotinamide adenine dinucleotide (NAD⁺) glycohydrolase, increases in old murine macrophages after infection compared to young controls. We aimed to determine whether the increase in CD38 in old murine macrophages after infection is directly associated with enhanced inflammation induced by the oral pathogens Aggregatibacter actinomycetemcomitans (Aa) or Porphyromonas gingivalis (Pg) when compared to young controls. Additionally, we determined the effects of a specific CD38 inhibitor (78c) on CD38, NAD⁺, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α expressions, and anti-oxidative responses in old murine macrophages induced by oral pathogens. Old and young murine macrophages were either uninfected or infected with the oral pathogens Aa or Pg for 1 to 24 h. Protein levels of CD38 and protein kinases, including nuclear factor kappa-B (NF-κB), phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinases (MAPKs), NAD⁺, and inflammatory cytokine (IL-1β, IL-6, TNF-α) levels were evaluated. Additionally, old murine macrophages were treated with a vehicle or a CD38 inhibitor (78c) and cells were either uninfected or infected with Aa or Pg. CD38, NAD⁺, cytokine (IL-1β, IL-6, TNF-α) levels, reactive oxygen species (ROS), NAPDH oxidase 1 (Nox1), and anti-oxidative enzymes, including superoxide dismutase1 (Sod1), glutathione peroxidase 4 (Gpx4), Peroxiredoxin 1 (Prdx1), thioredoxin reductase 1 (Txnrd1), and catalase (Cat), were evaluated. The results showed that old murine macrophages significantly enhanced CD38 and reduced NAD⁺ levels 24 h after Aa or Pg infection compared to young controls. This enhanced CD38 in old murine macrophages was not directly correlated with the activation of protein kinases (NF-κB, PI3K, and MAPKs), nor the (IL-1β, IL-6, TNF-α) levels in macrophages. The inhibition of CD38 by 78c reduced CD38, enhanced NAD⁺ levels, attenuated IL-1β, IL-6 and TNF-α pro-inflammatory cytokine levels, reduced ROS and Nox1 expressions, and enhanced expressions of Sod1, Gpx4, Prdx1, Txnrd1, and Cat in old murine macrophages infected with Aa or Pg. These results suggest that the inhibition of CD38 by 78c is a promising therapeutic strategy to treat aging-associated periodontitis. Full article

Candida auris is an emerging multidrug-resistant fungal pathogen with a high affinity for skin colonization and significant potential for nosocomial transmission. This study aimed to develop and evaluate chitosan-based hydrogels loaded with nystatin and propolis as a topical antifungal strategy for skin decolonization of C. auris. The formulations were selected based on our previous results and optimized for cutaneous application. The internal structure of the hydrogels was investigated by polarized light microscopy, confirming the amorphous nature of propolis and the partial dispersion of nystatin. The antifungal activity was assessed against ten fluconazole-resistant C. auris strains. The CS-NYS-PRO1 formulation demonstrated the highest antifungal performance in the agar test, also reducing viable cell counts to undetectable levels within 6 h. Time–kill assays and SEM imaging confirmed the rapid fungicidal effect and revealed severe membrane disruption and cytoplasmic leakage. Molecular docking analyses indicated the strong binding of nystatin to both sterol 14α-demethylase (CYP51) and dihydrofolate reductase (DHFR) from C. auris, suggesting complementary membrane and intracellular mechanisms of action. These findings support the use of such hydrogels as a local, non-invasive, and biocompatible strategy for managing C. auris colonization, with promising implications for clinical use in infection control and the prevention of skin-mediated transmission in healthcare settings. Full article

This study links the traditional use of celery (Apium graveolens L.) and parsley (Petroselinum crispum L.) roots in Balkan cuisine and herbal medicine, along with the longstanding role of turmeric (Curcuma longa L.) rhizome in Ayurvedic and Asian medicinal practices, with modern technological approaches to develop a functional food formulation. A series of blend variations were evaluated for total phenolic content, antioxidant capacity, and sensory quality. The incorporation of turmeric significantly enhanced the antioxidant potential of celery–parsley mixtures. Celery–parsley–turmeric root blend (CPT6), comprising equal parts, was identified as optimal, exhibiting high total phenolic content (9.56 mg gallic acid equivalent/g), strong antioxidant activities, and a favourable sensory profile rated as “very good” (3.58 average score). CPT6 further demonstrated promising biofunctional properties, including potent α-amylase and α-glucosidase inhibition activities (72% and 80%, respectively), alongside moderate antihypertension activity (ACE) (62%) and hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibition (55%). Chemometric analyses (PCA) and machine learning modelling (ANN) confirmed the significant role of turmeric proportion in enhancing both bioactivity and consumer acceptability. This research highlights the synergy between tradition and technology in creating novel, multifunctional food ingredients suited for functional food and nutraceutical applications. Full article

Arazá (Eugenia stipitata) seeds, which are an abundant byproduct of pulp processing in the Amazon region, represent up to 84% of the fruit’s dry matter and remain underutilized. This study investigates, for the first time, the bioactive potential of hydroethanolic (70:30) extracts from Arazá seeds (ASs) to inhibit key enzymes related to glycemic and cholesterol regulation, specifically α-amylase, α-glucosidase, and HMG-CoA reductase. Additionally, the proximate characterization, antioxidant capacity assessment, and LC-MS analysis of phenolic compound composition were performed. The results demonstrated that the hydroethanolic extracts exhibited the significant inhibition of α-amylase and α-glucosidase, with IC₅₀ values of 47.06 and 49.99 µg/mL, respectively. This inhibitory activity correlates with the total phenolic content (155.88 ± 6.12 mg GAE/g dry weight) and compounds such as epicatechin gallate and p-hydroxybenzoic acid. The extract also showed a high capacity to scavenge the DPPH radicals (IC₅₀ = 46.63 µg/mL), although no inhibition of HMG-CoA reductase or cytotoxicity in blood cells was observed. Proximate analysis revealed that ASs are low in lipids (0.16%), proteins (4.96%), and ash (0.82%) but contain a considerable amount of fiber (27.7%). These findings suggest that ASs represent a valuable byproduct with potential for further research on its application in diabetes management. Full article

The Onocleaceae family, a small group within the Pteridophytes, comprises four genera, but has been phytochemically studied mainly for Pentarhizidium orientale, Pentarhizidium intermedium, and Matteuccia struthiopteris. To date, a total of 91 compounds have been isolated from these three species, including 15 flavonoids, 48 flavonoid glycosides, 6 stilbenes, 4 isocoumarins, 2 phthalides, 3 chromones, 2 lignan glycosides, 8 isoprenoid derivatives, and 3 phenolic compounds. Notably, most flavonoids and flavonoid glycosides possess C-methyl groups at the C-6 and/or C-8 positions, with several conjugated to (S)-3-hydroxy-3-methylglutaryl (HMG) moieties. Although not all isolates have been evaluated for their pharmacological activities, several compounds have demonstrated bioactivities such as antiviral, anti-inflammatory, α-glucosidase inhibitory, aldose reductase inhibitory, and antioxidant effects. Full article

This study investigated the phytochemical composition and biological activities of Myrtus communis essential oil (EO) from Algeria, focusing on its antimicrobial, antifungal, and insecticidal properties using in vitro and in silico approaches. Gas chromatography–mass spectrometry (GC-MS) analysis identified myrtenyl acetate (57.58%), 1,8-cineole (17.82%), and α-terpineol (6.82%) as the major constituents. M. communis EO exhibited significant antibacterial activity, particularly against Staphylococcus aureus (13.00 ± 0.70 mm) and Salmonella typhimurium (13.00 ± 1.50 mm), with moderate inhibition of Bacillus subtilis (10 ± 1.00 mm) and Escherichia coli (9.00 ± 0.70 mm), while Pseudomonas aeruginosa showed resistance. The antifungal activity was notable against Fusarium oxysporum (16.50 ± 0.50 mm), Aspergillus fumigatus (11.00 ± 1.00 mm), and Penicillium sp. (9.00 ± 0.60 mm) but ineffective against Aspergillus niger. Insecticidal activity against Tribolium castaneum was evaluated using contact toxicity, fumigation toxicity, and repellent activity assays. The EO demonstrated potent insecticidal effects, with an LC₅₀ value of 0.029 µL/insect for contact toxicity and 162.85 µL/L air for fumigation after 96 h. Additionally, the EO exhibited strong repellent activity, achieving 99.44% repellency at a concentration of 0.23 mg/cm² after 24 h. Density functional theory (DFT) calculations provided insights into the molecular geometry and electronic properties of the key bioactive compounds. Molecular docking studies evaluated their binding affinities to bacterial enzymes (DNA gyrase, dihydrofolate reductase6, and Gyrase B) and insecticidal targets (acetylcholinesterase), revealing strong interactions, particularly for geranyl acetate and methyleugenol. These findings highlight M. communis EO as a promising natural antimicrobial and insecticidal agent, with potential applications in plant protection and biopesticide development. Full article

The spraying time of nitrogen fertilizer is a key factor to consider when fertilizing with an intelligent micro-sprinkler irrigation system. This study aims to investigate the impact of nitrogen fertilizer spraying time on the seed oil quality of tree peony, with the expectation of providing theoretical support for the application of intelligent micro-sprinkler irrigation systems in the production of tree peony. In 2022 and 2023, foliar nitrogen application was conducted on Paeonia ostii ‘Fengdan’ utilizing an intelligent micro-spray irrigation system, with four distinct nitrogen fertilizer spraying times (3:00–4:00, 7:00–8:00, 14:00–15:00, and 19:00–20:00). Based on this, the study assessed nitrogen metabolism indicators in leaves and seeds at various growth stages and the fatty acid composition of seed oil in Paeonia ostii ‘Fengdan’. The results revealed that foliar nitrogen application between 14:00 and 15:00 significantly enhanced the levels of free amino acids (FAA), nitrate reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT) activity in both leaves and seeds. Furthermore, the ratio of α-linolenic acid in the seed oil was significantly increased. Correlation analysis demonstrated a positive or highly significant positive correlation between the levels of nitrogen metabolism indicators and the ratio of unsaturated fatty acids. In conclusion, foliar nitrogen application between 14:00 and 15:00 significantly enhances the FAA content and the activity of nitrogen metabolism enzymes within the leaves and seeds and promotes the synthesis of unsaturated fatty acids in seed oil. This study contributes to the efficient and high-quality cultivation of tree peony. Full article

Hawm Gra Dang Ngah rice (HDNR) is a red rice variety cultivated in Thailand’s southern border region, yet its biological properties have not been extensively studied. This study investigates the effects of HDNR extracts on bioactive constituents, spectral fingerprints, and antioxidant capacities. We evaluated the inhibitory effects of aqueous (HDNR-W) and ethanolic (HDNR-E) extracts on monoamine oxidase (MAO), α-glucosidase, and HMG-CoA reductase activities, as well as their cytotoxicity in normal and cancer cells. The results demonstrated that HDNR-E contained significantly higher concentrations of phenolic compounds, flavonoids, and anthocyanins compared to HDNR-W. In contrast, HDNR-W exhibited greater amino acid content than HDNR-E. FT-IR analysis revealed solvent-specific interactions that influenced compound solubility, highlighting distinct extraction efficiencies. Antioxidant assays showed HDNR-E to be markedly more potent, with superior performance in DPPH, ABTS, metal chelation, and FRAP assays, as evidenced by its lower IC₅₀ values relative to HDNR-W. Furthermore, HDNR-E displayed significantly stronger inhibitory activity against both MAO and α-glucosidase compared to HDNR-W. Conversely, HDNR-W demonstrated greater inhibitory efficacy toward HMG-CoA reductase than HDNR-E. Furthermore, HDNR-E exhibited significant antiproliferative effects against A549 lung cancer and MCF-7 breast cancer cells without affecting normal cells. These results highlight the potential of HDNR-E as a valuable source of bioactive compounds and underscore the importance of solvent selection in enhancing the health benefits of rice extracts. Full article

The leaf extract of Tectona grandis L.f. has shown potential as a 5α-reductase inhibitor, with two bioactive markers, namely (+)-eperua-8,13-dien-15-oic acid (1) and (+)-eperua-7,13-dien-15-oic acid (2), used for extract standardization. The purpose of this research was to investigate the in vitro skin penetration behavior of 1 and 2 in T. grandis leaf ethanolic extract solution and ready-to-use extract in propylene glycol (PG), and secondly, to determine their physicochemical properties, including partition coefficients and solubility. The appropriate vehicle for the in vitro skin penetration study was evaluated using the shake-flask method. The in vitro skin penetration study was conducted using the Franz diffusion cell model, and the amounts of the two active compounds in the extracts were analyzed using the HPLC method. Compounds 1 and 2 showed poor solubility in distilled water, whereas their solubility in HEPES buffer with 2% w/v of Tween 20 was significantly greater. The partition coefficient (log P_o/w) value for 1 was 5.77 ± 0.07, and for 2, it was 5.66 ± 0.02, indicating that both compounds are hydrophobic. After 24 h of an in vitro skin penetration study, 1 in both extracts showed significantly higher cumulative amounts (%) compared to 2. These findings suggest that 1 is more hydrophobic and readily penetrates the stratum corneum. When a PG enhancer was added, high cumulative amount trends of 1 and 2 in the ethanolic extract and extract in PG in the receiver compartment were detected after 24 h. These studies provide important insights that will guide the further development of products with T. grandis extracts for treating hair loss. Full article

Although yaks and cattle belong to the same Bovinae subfamily and have the same number of chromosomes, hybrid males are sterile because of the inactivation or abnormality of gene expression related to the production of healthy normal sperm. Recently, the analysis of gene expression not only in the testis but also in the epididymis has offered hints about the mechanism of infertility, because the epididymis supports the maturation of sperm in acquiring the capacity of fertilisation. Sperm maturation processes have been thought to be androgen-dependent, and the androgen receptor (AR) can be activated by dihydrotestosterone converted from plasma testosterone by the 5α-reductase isoform 2 (SRD5A2) in epididymal cells. In the present study, we investigated the immuno-expression levels of the AR and SRD5A2 in the epithelial cells of the hybrid cattle–yak epididymal caput in comparison with yak samples using image analysis. Epididymal tissues from yaks (1–3 years of age) and hybrid cattle–yaks (2 years of age) were used in this study. In yaks, AR signal intensity did not show any changes in epididymal epithelial cells during maturation. However, in 2-year-old hybrid cattle–yaks, AR signal intensity was significantly higher in the principal cells of the epididymis compared to that of yaks of the same age, indicating that hybrid sterility is not likely related to AR deficiency in the epididymal epithelium. On the other hand, SRD5A2 signal intensity was stable during maturation in the epithelial cells of the yak epididymis. However, the epididymal SRD5A2 signal intensity in the epithelial cells of the hybrid cattle–yak was lower than that of the yak. This suggests that a deficiency in SRD5A2 production in the epididymis may result in hybrid infertility, as it can subsequently cause incomplete AR signal transduction and altered spermatozoa physiology. Full article

Riociguat is a soluble guanylate cyclase (sGC) activator that increases the levels of cyclic guanosine monophosphate (cGMP). cGMP is known to play a key role in regulating kidney function. This research sought to investigate the possible protective effects of riociguat on the kidneys in the context of chronic kidney disease (CKD). CKD was induced in male Wistar rats through adenine administration. A total of 24 rats were allocated into four groups and administered treatments over a period of 35 days. Group 1 received a normal diet and a vehicle (carboxymethylcellulose (0.5%)), serving as the control. Group 2 received adenine (0.25% w/w) in the feed and a vehicle. Groups 3 and 4 received adenine in the feed (0.25% w/w) plus riociguat (3 mg/kg/day) and riociguat (10 mg/kg/day), respectively. Adenine administration significantly elevated systolic blood pressure, plasma creatinine, urea, and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, adenine reduced creatinine clearance and increased the urinary albumin-to-creatinine ratio and urinary N-Acetyl-β-D-Glucosaminidase (NAG). Histopathologically, adenine caused renal tubular necrosis and fibrosis. Furthermore, adenine elevated the plasma concentration of interleukins (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α). Adenine significantly increased renal malondialdehyde (MDA) and reduced glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC). Treatment with riociguat attenuated adenine-induced hypertension, improved kidney function, and ameliorated histopathological changes. Riociguat also reduced kidney injury markers, inflammation, and renal oxidative stress. The renoprotective effect of riociguat is probably due to anti-inflammatory and antioxidant actions. This indicates that riociguat may have the potential to slow the progression of kidney damage in chronic kidney disease (CKD). Full article