Search Results (157)

This study elucidates the regulatory mechanisms of methoxy substitution and photoexcitation on the antioxidant properties of pterostilbene (PTE) versus resveratrol (RES), employing a combined approach of multi-reference calculations, density functional theory (DFT), time-dependent DFT (TD-DFT), and molecular docking. Spectral analysis indicates that trans isomers exhibit a significant redshift (~13 nm) and have oscillator strengths more than double those of cis isomers. A pivotal difference in photoisomerization kinetics was identified: methoxy substitution drastically lowers the isomerization barrier for RES, indicating that PTE is more readily photoisomerized. Regarding radical scavenging, thermodynamic data confirm that Hydrogen Atom Transfer (HAT) and Radical Adduct Formation (RAF) are spontaneous pathways; notably, the O1 site of trans-PTE serves as the optimal hydrogen donor. Conceptual DFT (CDFT) analysis reveals that photoexcitation triggers a dramatic electronic reconfiguration, particularly for cis-PTE, whose ionization potential in the S1 state drops sharply to 4.66 eV, accompanied by an increased softness of 0.38 eV⁻¹, rendering it a highly potent electron donor. Furthermore, molecular docking demonstrates that trans-PTE robustly occupies the Keap1 Kelch pocket (binding energy: −7.478 kcal/mol) to inhibit Nrf2 binding via its favorable planar geometry. Full article

Ovarian cancer remains a major cause of mortality in women aged 74 years and under. Dysregulation of the PI3K/AKT/mTOR and NFκB signaling pathways has been associated with poor outcomes and treatment resistance. This study evaluated three potential anticancer agents targeting these pathways: buparlisib (a pan-PI3K/mTORC1 inhibitor), SN32976 (a PI3K p110α inhibitor), and pterostilbene (a resveratrol analogue that downregulates PI3K/AKT and NFκB signaling). Their efficacy was tested in 3D collagen models of ovarian cancer, using SKOV3 and OVCAR8 cell lines, activated by tumor necrosis factor-alpha (TNFα) and lysophosphatidic acid (LPA). Using concentrations derived from 2D assays, viability, collagen gel sizes, secretion of interleukin 6/8 (IL-6/8) and signal pathway proteins were analyzed. All compounds were less effective in 3D models than in 2D cultures, with high cell viability maintained. TNFα and LPA did not significantly alter drug sensitivity, and collagen gel contraction was largely unaffected. While the compounds did not consistently change signaling protein levels, they generally reduced secretion of pro-inflammatory cytokines IL-6 and IL-8. Growth in 3D collagen gels conferred drug resistance on OVCAR8 but not SKOV3 models. Overall, these findings provide preclinical support for further investigation of SN32976 and pterostilbene in ovarian cancer models. Full article

Stilbenoids are plant-derived chemical compounds that are classified as phytoalexins; recent focus has been drawn, especially on astringin, piceid, piceatannol, pterostilbene, pinosylvin, and resveratrol. These substances have been extensively studied for a variety of beneficial properties, including their effects on pathogenic microorganisms, parasites, and viruses. In their antifungal capacity, they are effective against Aspergillus spp., Botrytis spp., Candida spp., Trichophyton spp., and other fungi; tested stilbenoids have exhibited fungicidal and fungistatic effects, and inhibition of biofilm formation. Against parasites, they are effective against Echinococcus spp., Leishmania spp., Schistosoma spp., Trypanosoma spp., Toxoplasma spp., among others. Relevant action mechanisms include a reduction in parasitic enzymatic activity and inhibition of proliferation. They are also effective against different DNA and RNA viruses; the relevant mechanisms comprise reduction in viral replication, inhibition of viral genome expression, and viral attachment to cells. The toxicity of stilbenoids has been reviewed in recent papers, and, in most cases, the effective concentrations applied are well below the toxicity limit. Full article

Multiple Myeloma is a malignancy of the plasma cells of the bone marrow. This cancer rapidly becomes refractory to many of the currently available chemotherapeutic regimens used against it, requiring an alternative option or supplementary therapy. Pterostilbene is a naturally occurring compound in a variety of commonly consumed plants that exhibits strong antioxidant properties and, lately, has shown increasing activity as an anti-neoplastic compound. A review of the literature published since 2015 on Google Scholar and PubMed was conducted, with a focus on randomized controlled trials and an exclusion of review articles, unless pertinent to pathophysiology of Multiple Myeloma or background on Pterostilbene as a compound. Though data is limited in the use of Pterostilbene as an agent to combat Multiple Myeloma, studies have shown that it, along with synthetic derivatives, can induce apoptosis and limit proliferation of Multiple Myeloma cell lines. While safety has been evaluated in several settings with promising results, for Pterostilbene to be considered as a supplementary treatment in Multiple Myeloma, safe and effective doses of the compound in this patient population must be investigated and established via pre-clinical and clinical trials in the future. Full article

Background: Spinal cord injury (SCI) represents a form of traumatic damage to the central nervous system, and oligodendrocytes play a central role in SCI recovery. Ferroptosis is a major factor in the pathophysiological development of SCI symptoms. Pterostilbene (Pte) has antioxidant, anti-inflammatory, and neuroprotective effects. This study aims to investigate the potential role of Pte in SCI. Methods: A SCI model of rats was constructed. The BBB score assessment, the footprint test, EC staining, immunofluorescence (IF), and Western blot (WB) were conducted to observe the neuroprotective effects of Pte. The factors of ferroptosis, such as Glutathione (GSH), Malondialdehyde (MDA), Fe²⁺, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), were assessed. Then, transcriptomic data, network pharmacology, molecular docking analysis, and the erastin-induced ferroptosis model of OLN-93 cell lines were used to investigate the mechanism of inhibiting ferroptosis by Pte. Results: Pte treatment restored motor function and spinal cord tissue in SCI rats. Furthermore, Pte dramatically decreased oligodendrocyte ferroptosis. Finally, we discovered that Pte can repair SCI by blocking ferroptosis via the Keap1/Nrf2/SLC7A11/GPX4 axis. Conclusions: Pte reduces lipid peroxidation via the Keap1/Nrf2/SLC7A11/GPX4 axis, which reduces the development of ferroptosis in oligodendrocytes and improves locomotor function in rats with SCI. Full article

The simultaneous HPLC method for quantifying Quercetin (Que), Thymoquinone (Thy), and Pterostilbene (Pte) aims at the precise measurement of these polyphenols alone or in complex mixtures, targeting their therapeutic potential in disorders such as diabetes and epilepsy. The method focuses on quantifying Que, Thy, and Pte, utilizing optimized reversed-phase HPLC conditions as per ICH Q2(R1) standards. Key validation aspects include linearity, specificity, precision, and accuracy, ensuring compliance for quality control in nanomedicine and nutraceuticals, and the method’s applications support pharmacokinetic studies and stability testing, contributing to personalized medicine and addressing pharmaco-resistance. The HPLC method development and validation were performed on a phenyl column using the mobile phase consisting of solvent A (0.1% orthophosphoric acid in HPLC water) and solvent B (acetonitrile) at a ratio of 55:45 in an isocratic elution mode at a flow rate of 1 mL/min and at a column temperature of 35 °C. Ultraviolet detection was measured at 254 nm. Moreover, the method was validated for accuracy, precision, linearity, specificity, and sensitivity. The retention time for tested Que, Thy, and Pte was observed at 4.15 min, 8.70 min, and 10.75 min, respectively. Limits of detection for Que, Thy, and Pte were 1.55 μg/mL, 2.40 μg/mL, and 70.79 µg/mL, whereas limits of quantification were 4.69 μg/mL, 7.28 μg/mL, and 214.52 µg/mL, respectively. Linearity and correlation coefficients for Que, Thy, and Pte were found in the range of 50–250 μg/mL (0.9999), 50–250 μg/mL (0.9999), and 620–3100 μg/mL (0.9996), respectively. A reasonable level of accuracy was indicated by the tested method suggesting extremely high recovery levels (98–102%). The separation of tested compounds was achieved within 11 min. The developed and validated RP-HPLC–UV method was successfully applied for the identification and quantification of Que, Thy, and Pte for their combined estimation in complex formulations. From the validation study, it was found that the tested method is specific, accurate, precise, reliable, and reproducible. Full article

Grapevine downy mildew is a major disease in vineyards all around the world, caused by the oomycete Plasmopara viticola (Berk. & M. A. Curtis) Berl. & De Toni. Normally, its control depends almost exclusively on chemical and copper-based fungicides, especially in high-incidence areas with high relative humidity and mild temperatures. However, the European Union is determined to reduce the application of these phytochemicals by at least 50% by 2030, forcing winegrowers to seek alternative low-input strategies for proper sanitary maintenance. Basic substances (BSs), described in European Regulation (EC) 1107/2009, stand out as promising alternatives, but their molecular mechanism of action remains mostly unknown. In this context, this study analyzed the genetic effect in grapevine plants of several commercial products composed of BSs (chitosan, soy lecithin, Equisetum arvense and Salix cortex). All products exhibited promising results, triggering the induction of similar defence mechanisms, which included pathogenesis-related proteins (PRs), involved in direct pathogen repression; stilbenes, capable of producing antimicrobial compounds such as resveratrol and pterostilbene; several hormones, including oxylipins, ethylene, salicylic acid and terpenes, mediating immune signalling; and genes related to structural features of the plant, such as lignin, callose, cellulose and cuticular wax, constituting a first physiological barrier against P. viticola. Disease severity reduction differed among treatments, with Salix cortex showing the highest efficacy (58%), followed by BABA (38%) and LESOY (35%), while LECI and CHIT had minor effects (<9%). Gene expression analyses revealed that Salix cortex modulated the highest percentage of genes (41%), followed by natural infection without treatment (32%), LESOY (27%), BABA (26%), LECI (23%) and CHIT (23%). In terms of defence mechanisms, Salix cortex promoted the most pathways, LESOY induced eight, BABA and LECI seven and CHIT five. Overall, these results indicate that BSs can modulate several defence pathways in grapevine, supporting their potential use as sustainable alternatives for controlling downy mildew. 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

Cardiovascular disease remains the world’s leading cause of death globally, and there is continuing interest in adjunct, diet-based strategies that may support vascular health alongside guideline-directed pharmacotherapy. Anthocyanin-rich berries are one such option: they are widely consumed, generally safe, and can provide substantial amounts of polyphenols in habitual diets. This narrative review focuses on two anthocyanin-rich species, blueberries (Vaccinium spp.) and haskap/blue honeysuckle (Lonicera caerulea L.), and examines the extent to which their intake may influence vascular endothelial function and cardiometabolic risk markers. For blueberries, which are typically dominated by malvidin- and delphinidin-based anthocyanins together with flavonols, phenolic acids and stilbenes such as pterostilbene, randomized controlled trials and meta-analyses have reported improvements in flow-mediated dilation, with modest effects on blood pressure and arterial stiffness in at-risk populations. Haskap berries, characterized by high levels of cyanidin-3-O-glucoside (C3G) and enriched in iridoids and vitamin C, have been studied mainly in cell and animal models, with early human data suggesting potential effects on vascular function, blood pressure and physical performance. Across both berries, emerging evidence indicates that vascular actions are mediated largely by gut- and host-derived phenolic metabolites rather than by transient circulating parent anthocyanins. We synthesize current knowledge on the phytochemical composition of blueberries and haskap, on molecular pathways implicated in endothelial protection (including NO/eNOS signaling, NRF2-mediated antioxidant defense, NF-κB-driven inflammation, lipoprotein metabolism and platelet activation), and on clinical outcomes related to vascular and cardiometabolic health. On this basis, we outline a mechanistic hypothesis that combined blueberry–haskap interventions could provide additive or synergistic effects on vascular function. This hypothesis is currently supported primarily by preclinical and indirect clinical evidence and should be regarded as hypothesis-generating, highlighting priorities for future mechanism-aware trials rather than constituting a practice-changing recommendation. Full article

Natural compound-based strategies have gained attention as alternatives to conventional antifungal therapies, particularly in the management of Candida infections affecting the oral cavity, such as denture stomatitis. Our aim was to investigate the antifungal activity of the polyphenol pterostilbene (PTE) on clinical Candida isolates and microcosm biofilms from denture stomatitis, as well as to evaluate its toxicity and therapeutic efficacy in Galleria mellonella. PTE exhibited fungicidal effects against Candida albicans and Candida dubliniensis at 32 µg/mL. Time-kill assays demonstrated complete inhibition of viability for both strains within 8 h of exposure. In addition, PTE exhibited broad-spectrum antimicrobial activity, significantly reducing the counts of streptococci, mutans streptococci, staphylococci, and yeasts within microcosm biofilms. In vivo, PTE showed no signs of toxicity in G. mellonella at concentrations up to 20× MIC. Prophylactic treatment with PTE enhanced larval survival in experimental candidiasis caused by both C. albicans and C. dubliniensis. Moreover, prophylactic treatment decreased the fungal burden of C. albicans in the G. mellonella hemolymph, while the recruitment of hemocytes involved in host defense mechanisms remained unaltered. In summary, PTE demonstrated antimicrobial activity against Candida planktonic cells and complex biofilms associated with denture stomatitis, exhibiting favorable biocompatibility and in vivo antifungal efficacy in G. mellonella model. Full article

Background: Paclitaxel (PTX), a taxane chemotherapy drug, is widely regarded as one of the most potent and clinically effective treatments for advanced and resistant cancers. However, paclitaxel’s poor bioavailability is attributed to its unfavorable physicochemical properties, including low solubility and permeability. Nanosizing and multidrug combination strategies have emerged as key approaches to enhance the formulation of such compounds. Pterostilbene (PTE), a polyphenolic compound, possesses extensive anti-cancer properties and favorable hydrogen bond formation sites. In this study, PTE was employed to co-assemble with PTX to improve its physicochemical properties and enhance therapeutic efficacy. Methods: Paclitaxel-pterostilbene nanoparticles (PTX-PTE NPs) were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Results: PTX-PTE nanoparticles significantly improved the water solubility (7fold increase) and cytotoxicity of paclitaxel in tumor cells. The enhanced antitumor efficacy was achieved through P-gp and CDK1 protein downregulation, increased drug accumulation, and cell cycle inhibition. Conclusions: These improvements are attributed to the nanoparticles’ amorphous structure and nanoscale properties. In addition, the combined use of PTX and PTE significantly enhanced the cytotoxicity against human non-small cell lung cancer A549 cells. PTX-PTE nanoparticles show promise for improving drug delivery and overcoming multidrug resistance in A549 cells. Full article

The relentless spread of antimicrobial resistance poses a severe threat to global public health, food safety, and environmental security. Natural products with potent antimicrobial activity offer prospective substitutes for traditional antibiotics and chemical preservatives. Here, we demonstrate that pterostilbene (PT), a natural dietary compound, exhibits rapid lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). PT displayed metabolism-independent bactericidal effects, effectively eradicating dormant persister cells within one hour, though its activity was partially attenuated under anaerobic conditions. Mechanistically, PT disrupted membrane integrity by increasing permeability, dissipating membrane potential, depleting cellular ATP, and suppressing reactive oxygen species (ROS) generation. Its efficacy was modulated by membrane phospholipid composition, with phosphatidylglycerol (PG) and cardiolipin (CL) critically influencing antimicrobial potency. Crucially, PT robustly inhibited MRSA biofilm formation in milk. These findings highlight PT’s potential as a structurally stable, natural antimicrobial for controlling resilient MRSA, particularly against biofilm-associated and persister subpopulations in food systems. Full article

Tropical forage crops vary widely in biochemical composition, resulting in inconsistent silage quality. Understanding how plant traits shape microbial and metabolic networks during ensiling is crucial for optimizing fermentation outcomes. Eight tropical forages—Sorghum bicolor (sweet sorghum), Sorghum × drummondii (sorghum–Sudangrass hybrid), Sorghum sudanense (Sudangrass), Pennisetum giganteum (giant Napier grass), Pennisetum purpureum cv. Purple (purple elephant grass), Pennisetum sinese (king grass), Leymus chinensis (sheep grass), and Zea mexicana (Mexican teosinte)—were ensiled under uniform conditions. Fermentation quality, bacterial and fungal communities (16S rRNA and ITS sequencing), and metabolite profiles (untargeted liquid chromatography–mass spectrometry, LC-MS) were analyzed after 60 days. Sweet sorghum and giant Napier grass showed optimal fermentation, with high lactic acid levels (111.2 g/kg and 99.4 g/kg, respectively), low NH₄⁺-N (2.4 g/kg and 3.1 g/kg), and dominant Lactiplantibacillus plantarum. In contrast, sheep grass and Mexican teosinte exhibited poor fermentation, with high NH₄⁺-N (6.7 and 6.1 g/kg) and Clostridium dominance. Fungal communities were dominated by Kazachstania humilis (>95%), while spoilage-associated genera such as Cladosporium, Fusarium, and Termitomyces proliferated in poorly fermented silages. Metabolomic analysis identified 15,827 features, with >3000 significantly differential metabolites between silages. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed divergence in flavonoid biosynthesis, lipid metabolism, and amino acid pathways. In the sweet sorghum vs. sheep grass comparison, oxidative stress markers ((±) 9-HODE, Agrimonolide) were elevated in sheep grass, while sweet sorghum accumulated antioxidants like Vitamin D3. Giant Napier grass exhibited higher levels of antimicrobial flavonoids (e.g., Apigenin) than king grass, despite both being dominated by lactic acid bacteria. Sorghum–Sudangrass hybrid silage showed enrichment of lignan and flavonoid derivatives, while Mexican teosinte accumulated hormone-like compounds (Gibberellin A53, Pterostilbene), suggesting microbial dysbiosis. These findings indicate that silage fermentation outcomes are primarily driven by forage-intrinsic traits. A “forage–microbiota–metabolite” framework was proposed to explain how plant-specific properties regulate microbial assembly and metabolic output. These insights can guide forage selection and development of precision inoculant for high-quality tropical silage. Full article

Diabetic retinopathy (DR), a leading cause of blindness in working-age adults, arises from chronic hyperglycemia-induced oxidative stress, inflammation, and vascular dysfunction. Current therapies such as laser photocoagulation, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and steroids target advanced stages but fail to prevent early neuronal and microvascular damage. Emerging evidence highlights oxidative stress as a key driver of DR pathogenesis, disrupting the blood-retinal barrier (BRB), promoting neurodegeneration and angiogenesis. Advances in imaging, particularly optical coherence tomography angiography (OCTA), enable earlier detection of neurodegeneration and microvascular changes, underscoring DR as a neurovascular disorder. Polyphenols, such as resveratrol, curcumin, and pterostilbene, exhibit multitarget antioxidant, anti-inflammatory, and anti-angiogenic effects, showing promise in preclinical and limited clinical studies. However, their low bioavailability limits therapeutic efficacy. Nanotechnology-based delivery systems enhance drug stability, tissue targeting, and sustained release, offering potential for early intervention. Future strategies should integrate antioxidant therapies and precision diagnostics to prevent early irreversible retinal damage in diabetic patients. Full article