Search Results (216)

Flavonoids serve as crucial plant antioxidants in drought tolerance, yet their antioxidant regulatory mechanisms within mycorrhizal plants remain unclear. In this study, using a two-factor design, trifoliate orange (Poncirus trifoliata (L.) Raf.) seedlings in the four-to-five-leaf stage were either inoculated with Funneliformis mosseae or not, and subjected to well-watered (70–75% of field maximum water-holding capacity) or drought stress (50–55% field maximum water-holding capacity) conditions for 10 weeks. Plant growth performance, photosynthetic physiology, leaf flavonoid content and their antioxidant capacity, reactive oxygen species levels, and activities and gene expression of key flavonoid biosynthesis enzymes were analyzed. Although drought stress significantly reduced root colonization and soil hyphal length, inoculation with F. mosseae consistently enhanced the biomass of leaves, stems, and roots, as well as root surface area and diameter, irrespective of soil moisture. Despite drought suppressing photosynthesis in mycorrhizal plants, F. mosseae substantially improved photosynthetic capacity (measured via gas exchange) and optimized photochemical efficiency (assessed by chlorophyll fluorescence) while reducing non-photochemical quenching (heat dissipation). Inoculation with F. mosseae elevated the total flavonoid content in leaves by 46.67% (well-watered) and 14.04% (drought), accompanied by significantly enhanced activities of key synthases such as phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), 4-coumarate:coA ligase (4CL), and cinnamate 4-hydroxylase (C4H), with increases ranging from 16.90 to 117.42% under drought. Quantitative real-time PCR revealed that both mycorrhization and drought upregulated the expression of PtPAL1, PtCHI, and Pt4CL genes, with soil moisture critically modulating mycorrhizal regulatory effects. In vitro assays showed that flavonoid extracts scavenged radicals at rates of 30.07–41.60% in hydroxyl radical (•OH), 71.89–78.06% in superoxide radical anion (O₂^•−), and 49.97–74.75% in 2,2-diphenyl-1-picrylhydrazyl (DPPH). Mycorrhizal symbiosis enhanced the antioxidant capacity of flavonoids, resulting in higher scavenging rates of •OH (19.07%), O₂^•− (5.00%), and DPPH (31.81%) under drought. Inoculated plants displayed reduced hydrogen peroxide (19.77%), O₂^•− (23.90%), and malondialdehyde (17.36%) levels. This study concludes that mycorrhizae promote the level of total flavonoids in trifoliate orange by accelerating the flavonoid biosynthesis pathway, hence reducing oxidative damage under drought. Full article

Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., commonly known as divaricate siler, is a well-known medicinal plant from the Apiaceae family. Its natural habitat is rapidly declining owing to the harvesting of its roots, used as fángfēng in traditional Oriental medicine. This underutilized herb may serve as a valuable source of bioactive phenolic compounds, which can potentially be influenced by salicylic acid (SA) elicitation—a practical method to increase the concentration of valuable substances in plants. A field study showed that foliar application of SA on one-year-old S. divaricata positively influenced the total phenolic content in the herb, with the highest increase observed at 1.0 mM SA. Liquid chromatography–mass spectrometry (LC–MS) data became increasingly complex with rising SA levels, identifying up to 48 compounds, including cinnamoyl quinic acids (CQAs), dihydrofurochromones (DFCs), and flavonol O-glycosides (FOGs), most reported for the first time in this species. The highest concentrations of CQAs, DFCs, and FOGs in plants treated with 1.0 mM SA were 83.14, 3.75, and 60.53 mg/g, respectively, compared to 42.76, 0.95, and 40.73 mg/g in untreated (0.0 mM SA) plants. Nine in vitro antioxidant assays revealed strong radical-scavenging and nitric oxide (NO)- and Fe²⁺-chelating activities in 1.0 mM SA-treated plants, indicating robust antioxidative properties of the S. divaricata herb. Thus, foliar application of SA considerably enriches the herb with target antioxidants, increasing its medicinal value, which is reflected in the plant’s biological response. This could potentially reduce the overexploitation of natural populations of S. divaricata, helping to preserve this valuable plant. Full article

A series of rivastigmine hybrids, incorporating rivastigmine fragments (RIV) and a set of different antioxidant scaffolds, were designed, synthesized, and evaluated as multifunctional agents for the potential therapy of Alzheimer’s disease (AD). In vitro bioactivity assays indicated that some compounds have very good antioxidant (radical-scavenging) activity. The compounds also displayed good inhibitory activity against cholinesterases, though the bigger-sized hybrids showed higher inhibitory ability for butyrylcholinesterase (BChE) than for acetylcholinesterase (AChE), due to the larger active site cavity of BChE. All the hybrids exhibited an inhibition capacity for self-induced amyloid-β (Aβ_1–42) aggregation. Furthermore, cell assays demonstrated that some compounds showed capacity for rescuing neuroblastoma cells from toxicity induced by reactive oxygen species (ROS). Among these RIV hybrids, the best in vitro multifunctional capacity was found for the caffeic acid derivatives enclosing catechol moieties (4AY5, 4AY6), though the Trolox derivatives (4AY2, 4BY2) presented the best cell neuroprotective activity against oxidative damage. Molecular-docking studies provided structural insights into the binding modes of RIV-based hybrids to the cholinesterases, revealing key interaction patterns despite some lack of correlation with inhibitory potency. Overall, the balanced multifunctional profiles of these hybrids render them potentially promising candidates for treating AD, thus deserving further investigation. Full article

Background/Objectives: This study aimed to investigate the antioxidant and anti-inflammatory properties of a Hand and Foot Soaking Formulary composed of ten medicinal plants, with curcumin as a major bioactive marker, to provide scientific validation for its traditional use. Methods: The formulation was evaluated for total phenolic and flavonoid contents, with curcumin quantified using HPLC. Antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. Cytotoxicity was evaluated in RAW264.7 cells using the MTT assay. Anti-inflammatory activity was determined by measuring nitric oxide (NO), PGE₂, TNF-α, IL-1β, and IL-6 levels in LPS-stimulated RAW264.7 macrophages using ELISA. Results: The Hand and Foot Soaking Formulary exhibited promising antioxidant and anti-inflammatory properties, consistent with its traditional use. Phytochemical analysis confirmed the presence of bioactive compounds, with measurable levels of total phenolics, flavonoids, and significant curcumin content. Antioxidant activity was demonstrated through free radical scavenging and ferric-reducing assays, while cytotoxicity testing in RAW264.7 macrophages indicated low toxicity (IC₅₀ = 48.61 ± 3.80 µg/mL). The formulary significantly reduced LPS-induced nitric oxide, PGE₂, TNF-α, IL-1β, and IL-6 production. These effects were comparable to turmeric extract and curcumin, though curcumin displayed higher potency. Conclusions: The Hand and Foot Soaking Formulary demonstrates antioxidant and anti-inflammatory properties in vitro, supporting its traditional use. Its polyherbal composition may offer synergistic effects and holds promise as a safe, natural topical remedy. Full article

This study offers a detailed assessment of the polyphenolic composition and antioxidant, anti-inflammatory, and cardioprotective properties of lyophilized extracts derived from the aerial parts of Agastache mexicana and Agastache scrophulariifolia. The polyphenolic content was determined through the quantification of total polyphenols, flavonoids, and caffeic acid derivatives, complemented by LC-MS profiling. The antioxidant activity was evaluated in vitro using DPPH and FRAP assays, while the in vivo antioxidant and anti-inflammatory effects were investigated in a rat model of turpentine-oil-induced acute inflammation. Cardioprotective potential was assessed in a separate rat model of isoprenaline-induced myocardial infarction. Phytochemical analysis revealed a complex polyphenolic profile for both species, with tilianin and rosmarinic acid identified as predominant compounds. In the DPPH assay, both extracts exhibited marked radical scavenging activity (IC₅₀: 65.91 ± 1.21 μg/mL for A. mexicana; 68.64 ± 2.48 μg/mL for A. scrophulariifolia). In the in vivo assays, the administration of the extracts significantly decreased pro-oxidant biomarkers (TOS, OSI, MDA, NO) and enhanced antioxidant markers (TAC, SH groups). Furthermore, the extracts led to a significant reduction in serum levels of GOT, GPT, and CK-MB in rats subjected to myocardial injury, supporting their cardioprotective efficacy. Overall, the results suggest that A. mexicana and A. scrophulariifolia represent promising natural sources of polyphenolic compounds with potential therapeutic value in oxidative-stress-related inflammatory and cardiovascular disorders. Full article

Obesity and its associated complications, including oxidative stress, pose significant global health challenges. Natural products offer a promising avenue for developing novel therapeutic strategies. In this study, we investigated the potential of Panax japonicus (T. Nees) C.A. Meyer, a traditional medicinal plant known for its antioxidant and anti-obesity properties. A methanol extract of Panax japonicus and its fractions were evaluated for their in vitro antioxidant activities (tested using DPPH and reducing power assays), pancreatic lipase (PL) inhibitory capacities, and underlying mechanisms of action. The results indicated that the ethyl acetate fraction of P. japonicus (PJEA) exhibited the greatest potency, demonstrating strong antioxidant activity and significantly inhibiting digestive enzyme activity (pancreatic lipase). Mechanistic studies revealed that the PL inhibition was of a mixed type, combining both competitive and non-competitive mechanisms. Furthermore, PJEA demonstrated the ability to inhibit the differentiation of preadipocytes, primarily exerting its anti-adipogenic effects by downregulating the mRNA expression of PPARγ and the gene expression of C/EBPα. In addition, the extract suppressed the gene expression of FAS and ACC in adipose tissue. Isolation of the bioactive compounds from PJEA identified kaempferol 3-O-α-L-rhamnoside and catechin, which potentially contribute to the observed anti-obesity effects. Overall, this study highlights P. japonicus as a promising natural ingredient for scavenging free radicals and managing obesity, suggesting its potential for development into functional foods or therapeutic agents. Full article

Large-scale blooms of Ulva prolifera severely impact coastal ecosystems and economic development. In addressing Ulva management, the development of high-value utilization approaches for this macroalga remains crucial. Compared to other marine algae, Ulva prolifera exhibits higher protein content with diverse amino acid profiles, and existing studies demonstrate that hydrolyzed Ulva prolifera proteins can yield biologically active peptides with functional potential. Conventional methods for producing bioactive peptides are often cost-intensive. Here, we employed in silico enzymatic hydrolysis to generate small peptides from Ulva prolifera protein. Through computer screening, molecular docking with the Keap1 protein, and molecular dynamics simulations, we identified a potential antioxidant peptide, DWS (Asp-Trp-Ser). Molecular docking and dynamics simulations revealed that DWS forms stable complexes with Keap1 by establishing hydrogen bonds and Pi bonds with conserved amino acid residues (Leu557, Gly558, Ile559, Val604, Val606, and Arg415). In vitro antioxidant assays demonstrated that DWS exhibits potent DPPH and ABTS radical scavenging activities as well as reducing power. Cellular experiments showed that DWS effectively alleviates LPS-induced oxidative stress and inflammation in RAW264.7 macrophages. Full article

This study aimed to produce antioxidant peptide fractions from Skipjack tuna (Katsuwonus pelamis) head by-products through enzymatic hydrolysis and membrane filtration. Raw materials were sequentially hydrolyzed with Alcalase^® (4 h) and Flavourzyme^® (1 h), reaching a final degree of hydrolysis of 18.5 ± 0.9%. The crude hydrolysate was fractionated using ceramic membranes with molecular weight cut-offs of 8, 3, and 1 kDa. Some peptide fractions presented a relevant proportion of short-chain peptides (>50% w/w) and free amino acids (>10% w/w), as well as a high content of essential amino acids (>64% mol), supporting their value as dietary ingredients for aquafeeds. In vitro antioxidant activities were assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferrous ion chelation assays. Some fractions (e.g., F3R1 with IC₅₀ = 1.04 ± 0.01 mg·mL⁻¹ for metal chelating activity) displayed significantly improved (p < 0.05) antioxidant properties compared to the unfractionated hydrolysate (IC₅₀ = 2.75 ± 0.08 mg·mL⁻¹). This may be linked to their molecular weight profile and hydrophobic amino acid content. These results demonstrate the potential of the proposed approach to obtain bioactive peptide fractions with functional properties for aquafeeds. Zootechnical trials are needed to assess their effects on feed utilization and in vivo mitigation of oxidative stress. Full article

Suk-SaiYasna (SSY) is a well-documented traditional Thai herbal formula in the Royal Scripture of King Narai’s Traditional Medicine. SSY contains Cannabis sativa leaves as a key ingredient and has traditionally been used to promote sleep, alleviate stress-related symptoms, and stimulate appetite. This study aimed to investigate the neuroprotective effects of SSY in a mouse model of unpredictable chronic mild stress (UCMS)-induced cognitive impairment and explore the underlying mechanisms, particularly antioxidant enzyme pathways. Behavioral tests, including the Y-maze test, novel object recognition test, and Morris water maze test, demonstrated that UCMS-exposed mice exhibited cognitive impairment compared to non-stress mice. However, SSY treatment significantly improved learning and memory performance in UCMS-exposed mice. Mechanistic studies revealed that SSY reduced lipid peroxidation in the hippocampus and frontal cortex, key brain regions affected by chronic stress. Furthermore, UCMS significantly reduced the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), whereas SSY treatment restored their activity, indicating antioxidative and neuroprotective effects in vivo. Gene expression analysis further revealed that SSY regulates oxidative stress via the Nrf2/Keap1 signaling pathway. In vitro studies using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay confirmed the radical scavenging activities of SSY and its herbal components, demonstrating significant antioxidant potential. Phytochemical analysis identified delta-9-tetrahydrocannabinol, delta-9-tetrahydrocannabinolic acid A, and cannabinoids as bioactive compounds in SSY, along with potent antioxidants such as gallic acid, myricetin, myristicin, piperine, costunolide, and gingerol. These findings suggest that the SSY formula mitigates UCMS-induced cognitive function through its antioxidant properties via multiple pathways, including radical scavenging activities, modulating the Nrf2-Keap1 pathway, inducing the expression of HO-1, NQO1 mRNAs, and other antioxidant enzymes. This work bridges traditional Thai medicine with modern neuropharmacology. Full article

The antioxidant capacity and modulation of oxidative stress by industrially processed açaí pulp extract from the Amazon (APEA) and its major anthocyanins, cyanidin 3-glucoside (C3G) and cyanidin-3-O-rutinoside (C3R), were evaluated as potential strategies for preventing cardiovascular diseases. The APEA was chemically characterized using ultrafast liquid chromatography-mass spectrometry (UFLC-MS), which revealed six main phenolic compounds. Notably, 9-(2,3-dihydroxypropoxy)-9-oxononanoic acid, acanthoside B, roseoside, cinchonine, and nonanedioate were identified for the first time in açaí extracts. In vitro antioxidant assays demonstrated that APEA exhibited strong DPPH- and ABTS-radical-scavenging activities (up to 80% inhibition and 65 mmol TE/100g DW, respectively) and showed ferrous- and copper-ion-chelating activities comparable to those of EDTA-Na₂ at higher concentrations (up to 95% inhibition). Hydroxyl and superoxide radical scavenging activities reached 80% inhibition, similar to that of ascorbic acid. In H₂O₂-treated H9c2 cardiomyocytes, APEA significantly reduced the intracellular ROS levels by 46.9%, comparable to the effect of N-acetylcysteine. APEA also attenuated menadione-induced oxidative stress in H9c2 cells, as shown by a significant reduction in CellROX fluorescence (p < 0.05). In vivo, APEA (100 mg/kg) significantly reduced CCl-induced hepatic lipid peroxidation (MDA levels), restored glutathione (GSH), and increased the antioxidant enzymes CAT, GPx, and SOD, demonstrating superior effects to C3G and C3R, especially after 21 days of treatment (p < 0.001). These findings suggest that Amazonian açaí pulp (APEA) retains potent antioxidant activity after industrial processing, with protective effects against oxidative damage in cardiomyocytes and hepatic tissue, highlighting its potential as a functional food ingredient with cardioprotective and hepatoprotective properties. Full article

Collagen peptides are recognized for their diverse bioactivities; however, efficiently screening potent peptides from hydrolysates remains challenging. This study employed an integrated strategy that combined in silico antioxidant activity prediction and molecular docking to myeloperoxidase (MPO) to screen active peptides derived from yak bone collagen hydrolysates. Focusing on low molecular weight peptides, containing motifs such as GVM, GLP, GPM, and GPQ, we identified nine antioxidant peptides (KC1–KC9). Their activities were validated through in vitro free radical scavenging assays, with peptide KC7 demonstrating superior performance. Furthermore, peptide KC7 promoted proliferation, differentiation, and mineralization in MC3T3-E1 cells by upregulating osteogenic markers such as Runx2 and osteocalcin, modulating the Wnt/β-catenin and PI3K/Akt pathways, and reducing the Bax/Bcl-2 ratio. These results highlight KC7’s dual capacity to mitigate oxidative stress and potentially reduce apoptotic susceptibility, thereby stimulating osteogenesis. This positions peptide KC7 as a promising candidate for bone regeneration and oxidative stress-related disorders. Moreover, this study underscores the effectiveness of integrating computational and experimental approaches for the discovery of multifunctional natural peptides. Full article

Substantial in vitro experimental data have been produced about the safety, antioxidant, neuro- and hepatoprotective effects of a series of recently synthesized N-pyrrolyl hydrazide-hydrazones (compounds 5, 5a–5g). However, compound activity across multiple assays varies and it is challenging to elucidate the favorable physicochemical characteristics of the studied compounds and guide further lead optimization. The aim of the current study is to apply exploratory data analysis in order to profile the biological effects of the novel hydrazide-hydrazones, gain insights related to their mechanisms of action in the context of in silico predictions and identify key predictor–outcome relationships. We collected a dataset from available in vitro studies of compounds 5, 5a–5g. It included cytotoxicity values, protection against hydrogen peroxide-induced damage in HepG2 and SH-SY5Y cells, two radical scavenging assays and a hemolysis assay across a range of treatment concentrations. SwissADME-based predictions of chemometric and ADME parameters and pro-oxidant enzyme docking data were generated to provide context for the interpretation of in vitro outcome patterns and identify causal relationships. Multiple factor analysis (MFA), followed by hierarchical clustering on principal components (HCPC), was applied to profile compounds’ biological behavior. This revealed that differences in the number of H-bond donors, in the permeability coefficient and in the docking scores to two pro-oxidant enzymes could aid in explaining the effects of compounds with similar in vitro profiles. HCPC differentiated 5a as mostly neuroprotective, 5 and 5d as hepatoprotective radical scavengers, 5g with higher docking affinity to 5-lipoxygenase (5-LOX) and myeloperoxidase (MPO) and 5b, 5c and 5f as having less H-bond donors and variable in vitro activity. The consensus application of three variable selection approaches based on standard lasso regression, robust penalized regression and random forest confirmed the relationships between some in vitro outcomes and LogP, pan-assay interference (PAINS) alerts, 5-LOX allosteric site docking and H-bond donor numbers. The exploratory analysis of the combined in vitro and in silico dataset provides useful insights which could help explain the major drivers behind the experimental results. It can be informative in the design of new, improved members of the series of novel N-pyrrolyl hydrazide-hydrazones with better neuroprotective potential and less side effects. Full article

This study investigates the antioxidative potential of pomegranate peel extract (PPE) and prickly pear peel extract (HPE) as natural preservatives in cooked chicken models. The extracts were characterized for their phenolic and tannin content, and their antioxidant activity was measured through in vitro chemical assays using ABTS, DPPH, and FRAP assays. Cooked chicken samples were formulated with different concentrations of PPE or HPE and compared to sodium nitrite (NaNO₂) treatment. The effects on lipid and protein oxidation, instrumental colour parameters, and aldehyde formation were evaluated during storage. The results demonstrated that PPE exhibited higher antioxidant activity compared to HPE, particularly at higher concentrations. PPE_300 had the highest phenolic content, exhibited the strongest radical scavenging activity, and significantly reduced lipid oxidation markers such as malondialdehyde and lipid hydroperoxides. PPE also preserved protein integrity by reducing carbonyl formation and maintaining thiol levels. Colour stability was improved in both PPE- and HPE-treated samples, although nitrite remained the most effective in maintaining redness (a*-values). These findings suggest that PPE, particularly at 300 mg/kg, is a promising natural alternative to synthetic antioxidants for improving oxidative stability and shelf life in meat products. Further research should explore sensory attributes and consumer acceptance to facilitate industrial applications. Full article

This study aimed to evaluate the protective effects of peach leaf extract (Prunus persica L.) against metabolic syndrome and oxidative stress in Wistar rats subjected to a high-fructose diet. The Wistar rats were divided into groups and fed a high-fructose diet, with or without supplementation of peach leaf extract. The extract was characterized by its bioactive compounds, including an organic acid yield of 53.8%, total phenolic content (TPC) of 273.36 ± 1.929 mg GAE/g DW, flavonoid content (TFC) at 149.02 ± 57.47 mg QE/g DW, condensed tannins (TCT) at 2.34 ± 0.171 mg CE/g DW, and flavonols at 81.67 ± 0.497 mg DE/g DW. In vitro tests showed significant antioxidant potential, with a total antioxidant capacity (TAC) of 44.11 ± 6.328 mg AAE/g DW, DPPH radical scavenging activity (IC₅₀ = 4.89 mg/mL), and reducing power assay (FRAP, IC₅₀ = 0.525 mg/mL). The results indicated that the extract significantly reduced body weight gain, plasma insulin levels (0.30 ± 0.00 U(IU)/mL), glycemia (0.955 ± 0.068 g/L), total cholesterol (0.555 ± 0.177 g/L), and triglycerides (0.720 ± 0.141 g/L). Regarding oxidative stress markers, the extract decreased levels of malondialdehyde (MDA, 4567 ± 121 μmol/L), hydroperoxides (1304 ± 288 μmol/L), and carbonylated proteins (0.029 ± 0.020 μmol/L), while increasing levels of vitamin C (25.84 ± 3.00 mg AAE/L), Oxygen Radical Absorbance Capacity (ORAC, 6.043 ± 0.345 UA), and catalase activity (0.0052 ± 0.00008 μL/mL). These findings suggest that P. persica L. may alleviate impairments related to metabolic syndrome by improving metabolic profiles and reducing oxidative stress in rats fed a high-fructose diet, making it a potential dietary supplement for managing metabolic syndrome. Full article

This study aimed to optimize the extraction of phytocompounds intended for wound care applications from three plant species, Sambucus nigra L. flowers and Epilobium hirsutum L. and Lythrum salicaria L. aerial parts, by using a Quality by Design approach. The effects of different extraction methods (ultra-turrax and ultrasonic-assisted extraction), ethanol concentrations (30%, 50%, 70%), and extraction times (3, 5, 10 min) were studied, and during the optimization step, the polyphenol and flavonoid contents were maximized. The phytochemical profiles of the optimized HEs (herbal extracts) were assessed using LC-MS/MS methods. The antioxidant capacity of the optimized HEs was determined using DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity) TEAC (Trolox equivalent antioxidant capacity), and FRAP (ferric reducing antioxidant power) assays, while the antibacterial activity was evaluated against Escherichia coli, Pseudomonas aeruginosa, and MSSA—methicillin-sensitive Staphylococcus aureus and MRSA—methicillin-resistant Staphylococcus aureus). Cell viability and antioxidant and wound healing potential were assessed on keratinocytes and fibroblasts. The anti-inflammatory effect was assessed on fibroblasts by measuring levels of interleukins IL-6 and IL-8 and the production of nitric oxide from RAW 264.7 cells. The major compounds of the optimized HEs were rutin and chlorogenic acid. The Lythrum salicaria optimized HE showed the strongest antibacterial activity, while the Sambucus nigra optimized HE demonstrated high cell viability. Lythrum salicaria and Epilobium hirsutum optimized HEs showed increased antioxidant capacities. All extracts displayed anti-inflammatory effects, and the Epilobium hirsutum optimized HE exhibited the best in vitro wound-healing effect. Full article