Search Results (217)

Reactive oxygen species (ROS) are often seen solely as harmful byproducts of oxidative metabolism, yet evidence reveals their paradoxical roles in both promoting and inhibiting cancer progression. Despite advances, precise context-dependent mechanisms by which ROS modulate oncogenic signaling, therapeutic response, and tumor microenvironment dynamics remain unclear. Specifically, the spatial and temporal aspects of ROS regulation (i.e., the distinct effects of mitochondrial versus cytosolic ROS on the PI3K/Akt and NF-κB pathways, and the differential cellular outcomes driven by acute versus chronic ROS exposure) have been underexplored. Additionally, the specific contributions of ROS-generating enzymes, like NOX isoforms and xanthine oxidase, to tumor microenvironment remodeling and immune modulation remain poorly understood. This review synthesizes current findings with a focus on these critical gaps, offering novel mechanistic insights into the dualistic nature of ROS in cancer biology. By systematically integrating data on ROS source-specific functions and redox-sensitive signaling pathways, the complex interplay between ROS concentration, localization, and persistence is elucidated, revealing how these factors dictate the paradoxical support of tumor progression or induction of cancer cell death. Particular attention is given to antioxidant mechanisms, including NRF2-mediated responses, that may undermine the efficacy of ROS-targeted therapies. Recent breakthroughs in redox biosensors (i.e., redox-sensitive fluorescent proteins, HyPer variants, and peroxiredoxin–FRET constructs) enable precise, real-time ROS imaging across subcellular compartments. Translational advances, including redox-modulating drugs and synthetic lethality strategies targeting glutathione or NADPH dependencies, further highlight actionable vulnerabilities. This refined understanding advances the field by highlighting context-specific vulnerabilities in tumor redox biology and guiding more precise therapeutic strategies. Continued research on redox-regulated signaling and its interplay with inflammation and therapy resistance is essential to unravel ROS dynamics in tumors and develop targeted, context-specific interventions harnessing their dual roles. Full article

In this study, we investigated the effects of air packaging, vacuum packaging and modified atmosphere packaging (CO₂/N₂: 80/20) on the purine metabolism and enzyme activities of refrigerated large yellow croakers. The results showed that modified atmosphere packaging significantly inhibited microbial growth, delayed adenosine triphosphate degradation and maintained higher IMP content (1.93 μmol/g on day 21) compared to the air packaging group (2.82 μmol/g on day 12). The total purine content increased with storage time, with hypoxanthine content increasing significantly and occupying most of the total content, which was the key factor for the elevation of purine, followed by adenine content showing a significant decreasing trend. Hypoxanthine accumulation was significantly suppressed in the modified atmosphere packaging group (2.31 μmol/g on day 18), which was much lower than that in the air packaging group (5.64 μmol/g), whereas xanthine and guanine did not show significant differences among the groups. The key enzymes xanthine oxidase and purine nucleoside phosphorylase were much less active in modified atmosphere packaging, effectively delaying the cascade reaction of inosine monophosphate → hypoxanthine → xanthine. The study confirmed that modified atmosphere packaging intervenes in purine metabolism through enzyme activity regulation, providing a theoretical basis for the preservation of low purine aquatic products. Full article

Piperine, a phytochemical alkaloid, exhibits notable anticancer properties in several cancer cell types. In this study, we investigated the mechanisms by which piperine induces cell death and apoptosis in colorectal cancer (CRC) cells, focusing on oxidative stress and key signaling pathways. Using MTT assay, flow cytometry, gene overexpression, and Western blot analysis, we observed that piperine significantly reduced cell viability, triggered G1 phase cell cycle arrest, and promoted apoptosis in DLD-1 cells. In addition, piperine effectively suppressed cell viability and induced apoptosis in other CRC cell lines, including SW480, HT-29, and Caco-2 cells. These effects were associated with increased intracellular reactive oxygen species (ROS) generation, mediated by the regulation of mitochondrial complex III, NADPH oxidase, and xanthine oxidase. Additionally, piperine modulated signaling pathways by inhibiting phosphoinositide 3-kinase (PI3K)/Akt, activating p38 and p-extracellular signal-regulated kinase (ERK). Pretreatment with antimycin A, apocynin, allopurinol, and PD98059, and the overexpression of p-Akt significantly recovered cell viability and reduced apoptosis, confirming the involvement of these pathways. This study is the first to demonstrate piperine induces apoptosis in CRC cells through a multifaceted oxidative stress mechanism and by critically modulating PI3K/Akt and ERK signaling pathways. Full article

The cigarette production from Nicotiana tabacum generates significant amounts of waste, with an estimated 68.31 million tons of pre- and post-harvest waste discarded annually. The pre-harvest waste includes the upper parts of the plant, inflorescences, and bracts, which are removed to help the growth of the lower leaves. This study explores the potential of apical leaves from Nicotiana tabacum var. Virginia, discarded during the budding stage (pre-harvest waste). The leaves were extracted using environmentally friendly solvents (green solvents), including distilled water (DW) and two natural deep eutectic solvents (NaDESs), one consisting of simple sugars, fructose, glucose, and sucrose (FGS) and the other consisting of choline chloride and urea (CU). The anti-inflammatory and anti-aging potential of these green extracts was assessed by the inhibition of key enzymes related to skin aging. The xanthine oxidase and lipoxygenase activities were mostly inhibited by CU extracts with IC₅₀ values of 63.50 and 8.0 μg GAE/mL, respectively. The FGS extract exhibited the greatest hyaluronidase inhibition (49.20%), followed by the CU extract (33.20%) and the DW extract (20.80%). Regarding elastase and collagenase inhibition, the CU extract exhibited the highest elastase inhibition, while all extracts inhibited collagenase activity, with values exceeding 65%. Each extract had a distinct chemical profile determined by LC-ESI-QTOF-MS/MS and spectrophotometric methods, with several shared compounds present in different proportions. CU extract is characterized by high concentrations of rutin, nicotiflorin, and azelaic acid, while FGS and DW extracts share major compounds such as quinic acid, fructosyl pyroglutamate, malic acid, and gluconic acid. Ames test and Caenorhabditis elegans assay demonstrated that at the concentrations at which the green tobacco extracts exhibit biological activities, they did not show toxicity. The results support the potential of N. tabacum extracts obtained with NaDESs as antiaging and suggest their promising applications in the cosmetic and cosmeceutical industries. Full article

Poplar leaves (Populi folium) are a herbal remedy traditionally used for the treatment of rheumatic diseases and prostate inflammation. The aim of our study was a comprehensive identification of secondary metabolites occurring in the leaves of Populus alba, Populus × candicans, and Populus nigra, in order to search for a source of raw plant material rich in active compounds. Total salicylate (TSC), flavonoid (TFC), and phenolic compound (TPC) contents were determined, and the antioxidant potential was assessed using DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline- 6-sulfonic acid) diammonium salt), and FRAP (ferric reducing antioxidant power) assays as well as 2D-TLC (two-dimensional thin layer chromatography) bioautography using DPPH, riboflavin-light-NBT (nitro blue tetrazolium chloride), and xanthine oxidase inhibition tests. Secondary metabolites present in the analyzed poplar leaves were identified under the developed HPLC-DAD-ESI/MS (high performance liquid chromatography with photodiode array detection and electrospray ionization mass spectrometric detection analysis conditions and using the 2D-TLC method. Among the 80 identified compounds, 13 were shown for the first time in the genus Populus. The most diverse and similar set of flavonoids characterized the leaves of P. × candicans and P. nigra, while numerous salicylic compounds were present in the leaves of P. alba and P. × candicans. All analyzed leaves are a rich source of phenolic compounds. The highest flavonoid content was found in the leaves of P. × candicans and P. nigra, while the leaves of P. alba were characterized by the highest content of salicylates. All examined poplar leaves demonstrated antioxidant potential in all the assays used, which decreased in the following order: P. nigra, P. × candicans, P. alba. Full article

Background: Varicose veins and chronic venous insufficiency are chronic venous disorders involving abnormalities in the venous system. Inflammation, an increase in proteolytic enzymes, and free radicals are important factors that play a role in the varicose vein pathology. Methods: In this study, the antioxidant properties and inhibitor activities of 17 plant extracts used to treat varicose veins in traditional medicine were evaluated against varicose veins-related enzymes (hyaluronidase, elastase, collagenase, lipooxygenase, prolylendopeptidase, and xanthine oxidase). The most effective compounds responsible for the activity of the Helichrysum plicatum subsp. plicatum extract were isolated by open column chromatography techniques. The active compounds were determined to be naringenin, apigenin, and luteolin by spectroscopic methods. In the activity-guided isolation study, the xanthine oxidase enzyme inhibition method was used. Results: The fractions containing naringenin and apigenin (IC₅₀ = 0.269 ± 0.009 µg/mL) and apigenin and luteolin (IC₅₀ = 0.285 ± 0.019 µg/mL) compounds showed synergistic and strong effects against xanthine oxidase and were found to be as active as the positive control allopurinol (IC₅₀ = 0.250 ± 0.006 µg/mL). In the LC-MS/MS analysis of the Helichrysum plicatum extract, quinic acid (22.649 mg compound/g extract), chlorogenic acid (14.573 mg/g extract), isoquercitrin (14.371 mg/g extract), cosmosin (9.885 mg/g extract), and astragalin (11.506 mg/g extract) were detected as the major components. Naringenin, apigenin, and luteolin were detected at concentrations of 1.457, 2.518, and 1.368 mg/g in the extract, respectively. Conclusions: In conclusion, it is predicted that the combination of naringenin, apigenin, and luteolin has a promising use as a conservative treatment option for diseases associated with varicose veins due to their synergistic effects with each other. Full article

Hyperuricemia (HUA) is a metabolic disorder characterized by excessive uric acid (UA) production and impaired excretion. Goji, as a representative medicinal food, holds significant research and development value, while probiotic fermentation technology is finding increasingly widespread applications in the functional food sector. This study developed a novel goji fermented with three probiotic strains (Lactoplantibacillus plantarum CGMCC8198, Lactococcus lactis LTJ28, and Lactocaseibacillus casei YR2-2) and investigated its anti-HUA effects. Optimal fermentation conditions (7.913 material–liquid ratio, 3.92% inoculation, 7.49 h at 37 °C with 1:1:2 strain ratio) yielded a beverage with enhanced flavor profiles (19 aroma compounds) and high viable counts. In HUA cell models, the 15% fermented goji juice significantly reduced UA levels by 56% (p < 0.01). In potassium oxonate-induced HUA mice, the beverage effectively lowered serum UA, xanthine oxidase activity, and renal function markers (blood urea nitrogen and creatinine, p < 0.0001) while improving hepatic parameters (alanine aminotransferase, aspartate Aminotransferase). The goji-fermented juice significantly reduced the expression of renal UA transporters GLUT9 and URAT1 (p < 0.0001) while improving gut microbiota composition, as evidenced by increased beneficial SCFAs (acetic acid, butyric acid, p < 0.0001) and elevated Lactobacillus abundance 2.14-fold. Our findings demonstrate that this triple-probiotic-fermented goji beverage represents an effective dietary strategy for HUA management by simultaneously inhibiting UA production, enhancing excretion, and restoring gut microbiota homeostasis, providing a scientific basis for developing probiotic-based functional foods against HUA. Full article

Objective: Study the mechanism of ginsenoside Rg₁ in ameliorating hyperuricemia (HUA) induced by high-purine diet. Methods: Rats were randomly divided into groups, and the HUA model was established by administering a high-purine diet containing potassium oxonate combined with yeast. After the experiment, blood was collected via cardiac puncture, and the organ indices of the rats were calculated. Serum biochemical markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), xanthine oxidase (XOD), creatinine (CREA), uric acid (UA), and blood urea nitrogen (BUN) were measured. Histopathological sections of the kidney and intestine were prepared. Western blot was used to assess the expression levels of intestinal occludin and zonula occludens-1 barrier proteins and key proteins in IL-17/NF-κB inflammatory pathways. After the experiment, fecal samples were collected from the rats. The gut microbiota of HUA-induced rats was analyzed via 16S rRNA sequencing, and the levels of short-chain fatty acids in the fecal samples were quantified using gas chromatography–mass spectrometry. Results: Ginsenoside Rg₁ significantly increased body weight and organ indexes as well as reduced serum levels of BUN, CREA, ALT, AST, XOD, and UA. Pathologic analysis showed that ginsenoside Rg₁ improved renal cell injury, glomerulosclerosis, and renal interstitial fibrosis while restoring intestinal barrier function. Ginsenoside Rg₁ down-regulated the expression of inflammatory proteins and up-regulated the levels of intestinal barrier proteins. The results of 16S rRNA sequencing showed that ginsenoside Rg₁ significantly increased the diversity index of gut microbiota and enhanced the number of beneficial bacteria in HUA rats. Short-chain fatty acids analysis demonstrated that ginsenoside Rg₁ markedly elevated the levels of acetate, propionate, butyrate, and valerate in HUA rats. Conclusions: Ginsenoside Rg₁ ameliorates and treats HUA by improving the composition of intestinal flora and inhibiting the IL-17/NF-κB signaling pathway to reduce inflammatory factors in the intestinal tract in HUA rats. Full article

Background: Hyperuricemia (HUA) is a widespread metabolic disorder that arises from disruptions in purine metabolism, impaired kidney function, or both conditions. FPAW (Phe-Pro-Ala-Trp) is a novel peptide identified from Trachinotus ovatus with great XOD (xanthine oxidase) inhibitory activity (IC₅₀ = 3.81 mM), which can be developed as a potential active ingredient to relieve hyperuricemia. However, it remains unclear whether FPAW alleviates HUA in vivo or not. Methods: In this study, potassium-oxonate-induced hyperuricemic mice were used to evaluate the in vivo anti-hyperuricemic activity of FPAW. Some physiological parameters, such as serum uric acid (SUA), serum creatinine (SCR), blood urea nitrogen (BUN), and the activity of XOD and ADA (adenosine deaminase) in the liver were determined to evaluate the effect of reduced uric acid. The modulations in the gut microbiota and its metabolites (SCFAs) were analyzed by sequencing the V3-V4 region of the 16S rRNA gene and GC-MS in different fecal samples. Molecular docking was used to predict the interactions between the enzymes and FPAW. Results: The results showed that FPAW reduced the levels of serum uric acid, serum creatinine, and blood urea nitrogen, while also suppressing the activity of XOD in the livers of HUA mice. Moreover, the FPAW treatment alleviated gut microbiota dysfunction and increased the production of short-chain fatty acids to protect normal intestinal function and health of the host. Molecular docking simulations revealed that FPAW inhibited XOD activity by entering the hydrophobic channel and interacting with amino acid residues on the surface via hydrogen bonding and hydrophobic interactions. Conclusions: This study provides new candidates for the development of hypouricemic drugs. FPAW exhibited great potential to relieve hyperuricemia of mice induced by diet in the animal experiment. Full article

Background: Hyperuricemia is a prevalent metabolic disorder characterized by elevated serum uric acid (UA) levels. Methods: In this study, hydrolysate (SPP) derived from silkworm pupae protein was isolated and identified, demonstrating anti-hyperuricemic activity. The research aimed to investigate its anti-hyperuricemic and nephroprotective effects, along with potential mechanisms, through in vitro assays and in vivo experiments using potassium oxonate/hypoxanthine-induced hyperuricemic mice. Results: The SPP exhibited significant xanthine oxidase (XOD) inhibitory activity, with an IC₅₀ value of 7.41 mg/mL. Furthermore, SPP administration effectively reduced serum UA, blood urea nitrogen (BUN), creatinine levels, and renal pro-inflammatory cytokines in hyperuricemic mice. Mechanistic studies revealed that the anti-hyperuricemic effects of SPP may involve XOD inhibition and the modulation of renal UA transporters, specifically upregulating organic anion transporter 1 (OAT1) and ATP-binding cassette subfamily G member 2 (ABCG2) expression. Histopathological analysis and inflammatory cytokine profiling further demonstrated that SPP alleviated renal inflammation and pathological damage. Conclusions: These findings suggest that SPP possesses a notable urate-lowering efficacy and renal protective properties, highlighting its potential as a therapeutic agent for the management and prevention of hyperuricemia (HUA). Full article

Hyperuricemia, induced by monosodium urate (MSU) crystals that accumulate in articular joints and periarticular soft tissues, can impair macrophages. Possible causes of macrophage injury include uric acid-induced oxidative stress or inflammation. This study examined the dried fruits of guava (DFG) as a complementary medicine with urate-lowering properties, utilizing THP-1 macrophages to determine if high uric acid-induced cellular damage could be mitigated through the reduction of oxidative stress and inflammation via treatment with a phytochemical extract. The active extract was prescreened using a xanthine oxidase (XO) inhibition assay coupled with fractionation and component analysis. The DFG extracts were used to identify, through an in vitro study of THP-1 cells. The results indicated that the DFG extracts with the highest total flavonoids (12.08 ± 0.81 mg/g DW) exhibited the XO inhibition activity. High-performance liquid chromatography–tandem mass spectrometry analysis showed that DFG extract contained 85.32% flavonoids, including quercetin and kaempferol derivatives. Furthermore, fractionation results of DFG extracts indicated a significant reduction in MSU-induced cytotoxicity in THP-1 cells obtained from the 75% ethanol-eluted fraction (Fr-75). Additionally, kaempferol, an active compound in Fr-75, effectively mitigated MSU-induced NF-κB and NLRP3 gene overexpression. These findings suggest that the prepared Fr-75 is a promising hyperuricemia therapeutic candidate. Full article

This study investigated the protective effects of a polyherbal tea (PHT) on intestinal injury in hyperuricemia (HUA) mice and the underlying mechanisms. PHT was orally administered to mice for 49 days, while potassium oxonate and hypoxanthine were administered 7 days after PHT administration and continued for 42 days to cause HUA. Treatment with PHT significantly reduced serum uric acid and blood urea nitrogen levels in HUA mice. It also inhibited liver xanthine oxidase activity and promoted intestinal uric acid excretion through the upregulation of transporters GLUT9 and ABCG2. Intestinal barrier integrity was reinforced, as evidenced by the restoration of the villous structure, reduction in edema, and upregulation of tight junction proteins (occludin, ZO-1) and mucin (MUC2). Moreover, PHT suppressed serum LPS levels and inhibited the NF-κB pathway, leading to a reduction in TNF-α and IL-6 levels in the gut. Gut microbiota analysis revealed PHT reversed dysbiosis, enriching beneficial bacteria like Duncaniella sp. and Heminiphilus faecis. By UPLC–MS analysis, 154 compounds of PHT persisted in the gut, suggesting that these compounds are likely to modulate both intestinal barrier function and gut microbiota. These findings suggest that this PHT may have potential as a functional food for the prevention of hyperuricemia. Full article

We used molecular docking to determine the binding energy and interactions of apigenin and 16 related flavonoids, with 24 distinct proteins having diverse biological functions. We aimed to identify potential inhibitors of these proteins and understand the structural configurations of flavonoids impacting their binding energy. Our results demonstrate that apigenin exhibits high binding energies (a surrogate for binding affinity or inhibitory potential) to all tested proteins. The strongest binding energy was −8.21 kcal/mol for p38 mitogen-activated protein kinases, while the weakest was −5.34 kcal/mol for cyclin-dependent kinase 4. Apigenin and many other flavonoids showed high binding energies on xanthine oxidase (1.1–1.5 fold of febuxostat) and DNA methyltransferases (1.1–1.2 fold of azacytidine). We uncovered high binding energies of apigenin and certain flavonoids with mutated Kirsten rat sarcoma viral oncogene homolog at G12D (KRAS G12D), G12V, and G12C. Consequently, apigenin and certain flavonoids have the potential to effectively inhibit pan-KRAS oncogenic activity, not just on specific KRAS mutations. Apigenin and certain flavonoids also have high binding energies with aromatase (involved in estrogen production) and bacterial infections, i.e., DNA gyrase B and 3R-hydroxy acyl-ACP dehydratase (FABZ). Our findings are pivotal in identifying specific flavonoids that can effectively inhibit targeted proteins, paving the way for the development of innovative flavonoid-based drugs. Full article

Background: Acne is a prevalent dermatological condition characterized by the blockage of hair follicles and sebaceous glands, leading to the formation of acne. The anaerobe pathogen Cutibacterium acnes (formerly known as Propionibacterium acnes) plays an essential role in the pathogenesis of acne, for which generally antimicrobial treatment is required. Acne is a substantial health concern, and continuing research is being conducted to discover novel and efficacious remedies. The antimicrobial activity of plants has been demonstrated in numerous studies, and they are still targeted organisms in drug development. Studies showing that plants are effective against acne pathogens have also been reported. Methods: The antimicrobial activity of the hydroethanolic extracts prepared from 30 plant species was determined against C. acnes standard strains (C. acnes Scholz and Kilian ATCC 11827 and ATCC 11828) and 30 clinical isolates in our preliminary screening. Since acne is an inflammatory skin disease, the anti-inflammatory effect of six active extracts against C. acnes was determined through the in vitro inhibition of collagenase, lipoxygenase (LOX), hyaluronidase and xanthine oxidase (XO) enzymes. Results: Cotinus coggygria Scop. leaf extract displayed the highest hyaluronidase and collagenase inhibition (79.75% and 52.52%, respectively), while the extract from the aerial parts of Helichrysum arenarium (L.) Moench demonstrated a potent XO inhibitory effect (82.51%). Therefore, these two extracts have been chosen for further studies, and LC/MS-MS was used to determine the phenolic profiles of these extracts. Conclusions: Subsequently, nanoemulgels were formulated with the active extracts to develop a prototype herbal anti-acne product, and characterization studies of the formulations were conducted. Full article

Hedeoma piperita Benth. (Lamiaceae) is a native medicinal plant from Mexico. It grows in pine, oak, and oyamel forests, as well as grasslands. In the Purépecha Plateau of Michoacán, it is called quiensabe and traditionally used to treat stomach pain, colic, cough, and low blood pressure, among other ailments. This study aimed to determine the phytochemical profile of infusions and ethanolic extracts of the stems and green and purple leaves of H. piperita collected in Cherán, Michoacán. Total phenols, flavonoids, anthocyanins, and terpenoids were analyzed using UV–visible spectrophotometry; specific phenolic acids and flavonoids were detected by high performance thin layer chromatography (HPTLC); and the volatile profile of stems, green and purple leaves was determined by solid phase microextraction in GC-MS. Biological activities such as antioxidant activities (via DPPH and ABTS methods), antihypertensive activities (angiotensin converting enzyme (ACE) inhibition), antibacterial activities (minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC), anti-inflammatory activities (xanthine oxidase enzyme (XOD) inhibition) and antidiabetic activities (α-glucosidase enzyme inhibition) were evaluated in vitro. Results showed key compounds like rosmarinic acid, luteolin, menthone, menthol, and pulegone were identified using HPTLC and SPME/GC-MS, with organ-specific variations. Green and purple leaves infusions inhibited DPPH and ABTS⁺ by 90–99% (IC₅₀ 3.3–3.8 and 7.4–11.5 µg/mL, respectively) and purple leaves infusion showed a 69.88% XOD enzyme inhibition (IC₅₀ 47.991 µg/mL) and an 85.12% α-glucosidase enzyme inhibition (IC₅₀ 72.49 µg/mL). Purple leaves ethanolic extract exhibited the lowest MIC and MBC against Shigella flexneri and ACE inhibition at 97.25% (IC₅₀ 11.19 µg/mL). These results demonstrate the biological potential of H. piperita in the development of natural drugs and expand its use as an herbal remedy. Full article