Search Results (19)

Most approved drugs for Alzheimer’s disease (AD) are indicated for early to moderate stages and primarily target amyloid-beta or neurotransmitter systems. While these treatments may slow cognitive decline, they do not halt disease progression and are often limited by high cost and modest efficacy. Natural compounds are increasingly being explored as alternative interventions. Our previous study showed that oral administration of Avenanthramide-C (Avn-C), a natural polyphenol from oats, for 14 days from early AD stages improved cognition and reduced neuroinflammation in AD mice. To assess its long-term potential, in this study we extended Avn-C treatment to three months starting from early disease stages in 5xFAD and Tg2576 models. Sustained administration preserved recovered long-term potentiation (LTP) by maintaining AMPK activation and inhibiting caspase-3 and GSK3β, thereby reducing amyloid accumulation and tau hyperphosphorylation in the hippocampus. Avn-C also maintained anti-inflammatory effects by suppressing NF-κB-mediated proinflammatory cytokine release and preventing chronic microglial activation. This promoted microglial coverage of plaques in vivo and enhanced phagocytosis in vitro. Our findings suggest that early and sustained Avn-C treatment preserves cognitive function, modulates multiple pathological pathways, and may slow or prevent AD progression by targeting early neurodegenerative processes before irreversible damage occurs. Full article

With increasing research, the nutritional value of oats is gaining recognition. Fermentation is an emerging biotransformation pattern that changes the nutritional structure of whole grains. Currently, research on whole-grain fermentation is relatively focused on phenolic compounds and their antioxidants, but less attention has been given to avenanthramides (Avns) and the glycemic index (GI) in fermented oats. In this study, oats were subjected to solid-state fermentation (SSF) by Monascus purpureus for 21 days, and samples were taken at different time points. Changes in the contents of nutrients, phytochemicals, and antinutritional factors were analyzed using one-way ANOVA. Additionally, a simulated in vitro digestion experiment was conducted to assess the estimated glycemic index (eGI) of SSF oats. The results revealed that the nutritional structure of oats was changed by SSF, and the Avns content significantly increased, with 3.2 times more Avns in SSF oats than in unfermented oats, including 3.05, 3.09, 3.09, and 3.7 times more Avn A, Avn B, Avn C, and Avn D, respectively, and the eGI was reduced from 40.22 to 39.97 with increasing fermentation time. In general, SSF with Monascus purpureus has improved nutritional value, significantly increased the content of active ingredients, and reduced the level of eGI and two antinutritional factors (phytate and oxalate), which provides an effective way to improve the nutritional and digestive characteristics of oats. Full article

Exposure to tamoxifen can exert effects on the human liver, and esterases process prodrugs such as antibiotics and convert them to less toxic metabolites. In this study, the porcine liver esterase (PLE)-inhibitory activity of tamoxifen has been investigated. PLE showed inhibition of a PLE isoenzyme (PLE5). In addition, avenanthramides, which have a similar structure to that of tamoxifen, have been used to determine the PLE-inhibitory effect. Among the avenanthramide derivatives, avenanthramide B has been shown to inhibit PLE. Avenanthramide B interacts with Lys284 of PLE, whereas avenanthramide A and C counteract with Lys284. Avenanthramide B has shown a similar inhibitory effect to that of tamoxifen. Given that avenanthramide B can modulate the action of PLE, it can be used in pharmaceutical and industrial applications for modulating the effects of PLE. Based on superimposed structures between PLE and human liver esterase, the impact of tamoxifen use in humans is discussed. In addition, this study can serve as a fundamental basis for future investigations regarding the potential risk of tamoxifen and other drugs. Thus, this study presents an insight into the comparison of structurally similar tamoxifen and avenanthramides on liver esterases, which can have implications for the pharmaceutical and agricultural industries. Full article

Background: Oat-based Milk Alternatives (OMAs) provide multiple health benefits arising from oat’s unique compounds: avenanthramides, avenacosides, and dietary fibre β-glucan. Avenanthramides–polyphenols, unique to oats, provide anti-inflammatory and antioxidant effects, whilst avenacosides are saponins with anti-bacterial and anti-fungal properties. β-Glucans assist in lowering blood cholesterol and lead to the prevention of diabetes and cardiovascular diseases. However, oats undergo many stages of processing to ensure a sensory appealing and safe OMA product, including enzymatic treatment, heating, high shear, decanting of larger solids, and homogenisation. It is possible that throughout these stages, compounds may be affected by degradation or lost entirely. Objective: The concentration of avenanthramides, avenacosides, and β-glucans in the OMA samples was measured at each of the 12 stages of an OMA production, with a comparison of short ultra-heat treatment (UHT) and prolonged high heat treatment, to assess how they may be affected. Design: OMA samples were produced from basic ingredients within the pilot plant. Liquid chromatography–mass spectrometry was used to measure the concentration of avenanthramides and avenacosides. β-Glucan was determined spectrophotometrically using the Megazymes assay. Results: Avenanthramides and avenacosides were found to significantly increase in concentration after initial enzymatic treatment with alpha-amylase, whilst avenanthramides also increased post 90 °C treatment, and decanting – suggesting that these compounds are not being lost in the removed solids. However, avenanthramides decreased after UHT and prolonged heat treatment, suggesting they may be susceptible to degradation from prolonged heat and temperatures above 120 °C. β-Glucans concentrations decreased post glucoamylase treatment, and decanting – suggesting that β-glucans are lost within the decanted slurry, and increased after treatment with alpha-amylase, 90 °C and high shear mixing. Conclusion: With this information, future products may be optimised to preserve these components to improve the health benefits of oat-based milk alternatives. Full article

Cisplatin-induced ototoxicity leads to hearing impairment, possibly through reactive oxygen species (ROS) production and DNA damage in cochlear hair cells (HC), although the exact mechanism is unknown. Avenanthramide-C (AVN-C), a natural, potent antioxidant, was evaluated in three study groups of normal adult C57Bl/6 mice (control, cisplatin, and AVN-C+cisplatin) for the prevention of cisplatin-induced hearing loss. Auditory brainstem responses and immunohistochemistry of outer hair cells (OHCs) were ascertained. Cell survival, ROS production, Phospho-H2AX-enabled tracking of DNA damage-repair kinetics, and expression levels of inflammatory cytokines (TNF-α, IL-1β, IL6, iNOS, and COX2) were assessed using House Ear Institute-Organ of Corti 1 (HEI-OC1 Cells). In the in vivo mouse model, following cisplatin-induced damage, AVN-C decreased the hearing thresholds and sheltered all cochlear turns’ OHCs. In HEI-OC1 cells, AVN-C preserved cell viability and decreased ROS production, whereas cisplatin enhanced both ROS levels and cell viability. In HEI-OC1 cells, AVN-C downregulated IL6, IL-1β, TNF-α, iNOS, and COX2 production that was upregulated by cisplatin treatment. AVN-C attenuated the cisplatin-enhanced nuclear H2AX activation. AVN-C had a strong protective effect against cisplatin-induced ototoxicity through inhibition of ROS and inflammatory cytokine production and DNA damage and is thus a promising candidate for preventing cisplatin-induced sensorineural hearing loss. Full article

Oat consumption has increased during the last decade because of the health benefits associated with its soluble dietary fiber (β-glucan), functional proteins, lipids, and the presence of specific phytochemicals, such as avenanthramides. Oat is consumed mainly as whole grain, and the hull (seed coat), comprising 25–35% of the entire grain, is removed, generating a large amount of waste/by-product from the milling industry. The objective of this study was to evaluate the use of biotechnological strategies, such as sprouting for oat grain (OG) and hydrolysis for oat hull (OH), to enhance antioxidant and anti-inflammatory properties and lower the glycemic index (GI). Sprouting produced significant (p ≤ 0.05) increases in free (32.10 to 76.62 mg GAE (100 g)⁻¹) and bound phenols (60.45 to 124.36 mg GAE (100 g)⁻¹), increasing significantly (p ≤ 0.05) the avenanthramide (2c, 2p and 2f) soluble phenolic alkaloid content and anti-inflammatory properties of OG. On the other hand, the hydrolysis of OH using Viscoferm (EH2-OH) and Ultraflo XL (EH21-OH) increased by 4.5 and 5-fold the release of bound phenols, respectively; meanwhile, the use of Viscoferm increased the 4.55-fold soluble β-glucan content in OH, reaching values close to those of OG (4.04 vs. 4.46 g (100 g)⁻¹). The study shows the potential of both strategies to enhance the nutritional and bioactive properties of OG and OH and describes these processes as feasible for the industry to obtain an ingredient with high antioxidant and anti-inflammatory activities. Single or combined biotechnological tools can be used on oat grains and hulls to provide nutraceutical ingredients. Full article

Avena sativa L. is a wholegrain cereal and an important edible crop. Oats possesses high nutritional and health promoting values and contains high levels of bioactive compounds, including a group of phenolic amides, named avenanthramides (Avns), exerting antioxidant, anti-inflammatory, and anticancer activities. Epidermal growth factor receptor (EGFR) represents one of the most known oncogenes and it is frequently up-regulated or mutated in human cancers. The oncogenic effects of EGFR include enhanced cell growth, angiogenesis, and metastasis, and down-regulation or inhibition of EGFR signaling has therapeutic benefit. Front-line EGFR tyrosine kinase inhibitor therapy is the standard therapy for patients with EGFR-mutated lung cancer. However, the clinical effects of EGFR inhibition may be lost after a few months of treatment due to the onset of resistance. Here, we showed the anticancer activity of Avns, focusing on EGFR activation and signaling pathway. Lung cancer cellular models have been used to evaluate the activity of Avns on tumor growth, migration, EMT, and anoikis induced by EGF. In addition, docking and molecular dynamics simulations showed that the Avns bind with high affinity to a region in the vicinity of αC-helix and the DGF motif of EGFR, jeopardizing the target biological function. Altogether, our results reveal a new pharmacological activity of Avns as EGFR tyrosine kinase inhibitors. Full article

As a special polyphenolic compound in oats, the physiological function of oat avenanthramides (AVAs) drives a variety of biological activities, and plays an important role in the prevention and treatment of common chronic diseases. In this study, the optimum extraction conditions and structural identification of AVAs from oats was studied. The inhibitory effect of AVAs from oats on advanced glycation end-products (AGEs) in a glucose–casein simulation system was evaluated, and this revealed dose-dependent inhibitory effects. The trapping capacity of AVAs to the α-dicarbonyl compounds of AGE intermediate products was determined by HPLC–MS/MS, and the results indicate that AVA 2c, AVA 2p, and AVA 2f exhibited the ability to capture α-dicarbonyl compounds. More importantly, AVA 2f was found to be more efficient than AVA 2p at inhibiting superoxide anion radical (O₂⁻), hydroxyl radical (OH), and singlet oxygen (¹O₂) radical generation, which may be the main reason that AVA 2f was more efficient than AVA 2p in AGE inhibition. Thus, this research presents a promising application of AVAs from oats in inhibiting the food-borne AGEs formed in food processing. Full article

Uniquely, oats contain avenanthramides (AVAs), a group of phenolic alkaloids, exhibiting many health benefits. AVA analysis involves extraction with alcohol-based solvents and HPLC separation with UV and/or mass spectrometer detectors. There are many reported methods to extract AVAs. Almost all entail multiple extractions. The whole procedure is time- and labor-intensive. Furthermore, most quantifications are limited to three common AVAs (2f, 2p, 2c). The present study compared three extraction methods (all at 50 °C) for their effects on AVA concentrations and composition (% relative to total AVA) of oat grains. These included triplicate extractions with 80% ethanol containing 10 mM phosphate buffer (pH 2.0) (A), triplicate extractions with 80% ethanol (B), and a single extraction with 80% ethanol (C), while keeping solid/total solvent ratio at 1/60 (g/mL) and total extraction time of 60 min. Results showed that 80% buffered ethanol gave significantly lower AVA contents than 80% ethanol, while single and triplicate extractions with 80% ethanol produced the same extractability. However, the extraction method had no effect on AVA composition. Using 0.25 g sample size instead of 0.5 g saved extractants by half, without affecting AVA measurements. Consequently, a simplified method of extraction was developed, featuring Method C. The present study also expanded profiling individual AVAs beyond AVA 2c, 2p and 2f. Other AVAs identified and semi-quantified included 5p, 4p, 3f/4f, and 2pd. The simplified analysis was validated by measuring 16 selected oat grain samples. Some of these grains had relatively high contents of 4p, 3f/4f and 2pd, which have been considered minor AVAs previously. Full article

Memory deterioration in Alzheimer’s disease (AD) is thought to be underpinned by aberrant amyloid β (Aβ) accumulation, which contributes to synaptic plasticity impairment. Avenanthramide-C (Avn-C), a polyphenol compound found predominantly in oats, has a range of biological properties. Herein, we performed methanolic extraction of the Avns-rich fraction (Fr. 2) from germinated oats using column chromatography, and examined the effects of Avn-C on synaptic correlates of memory in a mouse model of AD. Avn-C was identified in Fr. 2 based on ¹H-NMR analysis. Electrophysiological recordings were performed to examine the effects of Avn-C on the hippocampal long-term potentiation (LTP) in a Tg2576 mouse model of AD. Avn-C from germinated oats restored impaired LTP in Tg2576 mouse hippocampal slices. Furthermore, Avn-C-facilitated LTP was associated with changes in the protein levels of phospho-glycogen synthase kinase-3β (p-GSK3β-S9) and cleaved caspase 3, which are involved in Aβ-induced synaptic impairment. Our findings suggest that the Avn-C extract from germinated oats may be beneficial for AD-related synaptic plasticity impairment and memory decline. Full article

Oats (Avena sativa L.) are rich in protein, fiber, calcium, vitamins (B, C, E, and K), amino acids, and antioxidants (beta-carotene, polyphenols, chlorophyll, and flavonoids). β-glucan and avenanthramides improve the immune system, eliminate harmful substances from the body, reduce blood cholesterol, and help with dietary weight loss by enhancing the lipid profile and breaking down fat in the body. β-glucan regulates insulin secretion, preventing diabetes. Progladins also lower cholesterol levels, suppress the accumulation of triglycerides, reduce blood sugar levels, suppress inflammation, and improve skin health. Saponin-based avanacosidase and functional substances of flavone glycoside improve the immune function, control inflammation, and prevent infiltration in the skin. Moreover, lignin and phytoestrogen prevent hormone-related cancer and improve the quality of life of postmenopausal women. Sprouted oats are rich in saponarin in detoxifying the liver. The literatures have been reviewed and the recent concepts and prospects have been summarized with figures and tables. This review discusses recent trends in research on the functionality of oats rather than their nutritional value with individual immunity for self-medication. The oat and its acting components have been revisited for the future prospect and development of human healthy and functional sources. Full article

Melanin causes melasma, freckles, age spots, and chloasma. Anti-melanogenic agents can prevent disease-related hyperpigmentation. In the present study, the dose-dependent tyrosinase inhibitory activity of Avenanthramide (Avn)-A-B-C was demonstrated, and 100 µM Avn-A-B-C produced the strongest competitive inhibition against inter-cellular tyrosinase and melanin synthesis. Avn-A-B-C inhibits the expression of melanogenesis-related proteins, such as TRP1 and 2. Molecular docking simulation revealed that AvnC (−7.6 kcal/mol) had a higher binding affinity for tyrosinase than AvnA (−7.3 kcal/mol) and AvnB (−6.8 kcal/mol). AvnC was predicted to interact with tyrosinase through two hydrogen bonds at Ser360 (distance: 2.7 Å) and Asn364 (distance: 2.6 Å). In addition, AvnB and AvnC were predicted to be skin non-sensitizers in mammals by the Derek Nexus Quantitative Structure–Activity Relationship system. Full article

Wholegrain oats contain a variety of phenolic compounds thought to help maintain healthy vascular function, through the maintenance of local levels of the vasodilator nitric oxide (NO). Thus, the full molecular mechanisms involved are not yet clear. With this work we aim to understand the possible cellular mechanisms by which avenanthramides and ferulic acid derivatives, present in oats, may help maintain a healthy vascular function through the modulation of the NO pathway. Primary Human Umbilical Vein Endothelial Cells (HUVEC) were exposed to ferulic acid, isoferulic acid, hydroferulic acid, ferulic acid 4-O-glucuronide, isoferulic acid 3-O-sulfate, dihydroferulic acid 4-O-glucuronide, avenanthramide A, avenanthramide B and avenanthramide C (1 μM) or vehicle (methanol) for 24 h. Apocynin and Nω-Nitro-L-arginine (L-NNA) were additionally included as controls. NO and cyclic GMP (cGMP) levels, superoxide production and the activation of the Akt1/eNOS pathway were assessed. The statistical analysis was performed using one-way ANOVA followed by a Tukey post-hoc t-test. Apocynin and all phenolic compounds increased NO levels in HUVEC cells (increased DAF2-DA fluorescence and cGMP), and significantly reduced superoxide levels. Protein expression results highlighted an increase in the Akt1 activation state, and increased eNOS expression. Overall, our results indicated that the glucuronide metabolites do not enhance NO production through the Akt1/eNOS pathway, thus all compounds tested are able to reduce NO degradation through reduced superoxide formation. Full article

Avenanthramides are a group of phenolic alkaloids that have been shown to have anti-inflammatory, anti-oxidant, anti-atherogenic, and vasodilation effects. The aim of the present study was to investigate the neuroprotective effect of avenanthramide-c (Avn-c) in focal brain ischemia and reperfusion injury using middle cerebral artery occlusion (MCAo) model with mice. Male C57BL/6 mice were divided into 4 groups: sham, control (MCAo), Avn-c, and Avn-c + LY294002 (phosphoinositide 3-kinase inhibitor) group. They were subjected to 60 min MCAo followed by reperfusion. Brain infarct volume and neurological deficit scores were measured after 24 h of reperfusion. We evaluated the blood brain barrier (BBB) integrity (ZO-1, VE-cadherin and occludin) and apoptosis (Bax, Bcl2, caspase3, Cytochrome C, and poly ADP ribose polymerase(PARP)-1). We also measured GSK3β for evaluation of the downstream mechanism of Akt. We examined the effect of the Avn-c in the phosphoinositide 3-kinase pathway. Avn-c reduced neurological score and infarction size. Avn-c inhibited the MCAo-induced disruption of tight junction proteins. Avn-c decreased apoptotic protein expression (Bax, Cytochrome C, and cleaved PARP-1) and increased anti-apoptotic protein expression (Bcl2) after MCAo. Akt and GSK3β were decreased in MCAo group and were restored in Avn-c group. This effect of Avn-c was abolished by PI3K inhibitor. In summary, Avn-c showed neuroprotective effects through PI3K-Akt-GSK3β signaling pathway. Full article

The consumption of fruits, vegetables, nuts, legumes, and whole grains has been associated with a lower risk of colorectal cancer (CRC) due to the content of natural compounds with antioxidant and anticancer activities. The oat (Avena sativa L.) is a unique source of avenanthramides (AVAs), among other compounds, with chemopreventive effects. In addition, oat germination has shown enhanced nutraceutical and phytochemical properties. Therefore, our objective was to evaluate the chemopreventive effect of the sprouted oat (SO) and its phenolic-AVA extract (AVA) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model. Turquesa oat seeds were germinated (five days at 25 °C and 60% relative humidity) and, after 16 weeks of administration, animals in the SO- and AVA-treated groups had a significantly lower inflammation grade and tumor (38–50%) and adenocarcinoma (38–63%) incidence compared to those of the AOM+DSS group (80%). Although both treatments normalized colonic GST and NQO1 activities as well as erythrocyte GSH levels, and significantly reduced cecal and colonic β-GA, thus indicating an improvement in the intestinal parameters, the inflammatory states, and the redox states of the animals, SO exerted a superior chemopreventive effect, probably due to the synergistic effects of multiple compounds. Our results indicate that oats retain their biological properties even after the germination process. Full article