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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.

Avenanthramides (Avns) and their derivatives, a group of polyphenolic compounds found abundantly in oats (Avena sativa Linn.), have emerged as promising candidates for neuroprotection due to their immense antioxidant, anti-inflammatory, and anti-apoptotic properties. Neurodegenerative diseases (NDDs), characterized by the progressive degeneration of neurons, present a significant global health burden with limited therapeutic options. The phosphoinositide 3-kinase (PI3K) signaling pathway plays a crucial role in cell survival, growth, and metabolism, making it an attractive target for therapeutic intervention. The dysregulation of PI3K signaling has been implicated in the pathogenesis of various NDDs including Alzheimer’s and Parkinson’s disease. Avns have been shown to modulate PI3K/AKT signaling, leading to increased neuronal survival, reduced oxidative stress, and improved cognitive function. This review explores the potential of Avn polyphenols as modulators of the PI3K signaling pathway, focusing on their beneficial effects against NDDs. Further, we outline the need for clinical exploration to elucidate the specific mechanisms of Avn action on the PI3K/AKT pathway and its potential interactions with other signaling cascades involved in neurodegeneration. Based on the available literature, using relevant keywords from Google Scholar, PubMed, Scopus, Science Direct, and Web of Science, our review emphasizes the potential of using Avns as a therapeutic strategy for NDDs and warrants further investigation and clinical exploration.

Oat is among the food crops and ancient grains cultivated and consumed worldwide. It is gaining in popularity owing to its nutritional composition and multifunctional benefits of select bioactive compounds. Beta-glucan is an important component of dietary fiber found in oat grains. It is the major active compound in oats with proven cholesterol-lowering and antidiabetic effects. Oats also provide substantial levels of other bioactive compounds such as phenolic acids, tocols, sterols, avenacosides, and avenanthramides. The consumption of oats has been determined to be beneficial for human health by promoting immunomodulation and improving gut microbiota. In addition, oat consumption assists in preventing diseases such as atherosclerosis, dermatitis, and some forms of cancer. While much has been published in relation to oat nutrients and oat fibers and their impact on major diseases, the oat industries and consumers may benefit from greater knowledge and understanding of clinical effects, range of occurrence, distribution, therapeutic doses and food functional attributes of other oat bioactives such as avenanthramides and saponins as well as other anti-inflammatory agents found in the cereal. This review focuses on the various studies relevant to the contribution of the consumption of oats and oat-based products in preventing human diseases and promoting human health.

Avenanthramides (Avns), polyphenols found exclusively in oats, are emerging as promising therapeutic candidates for the treatment of several human diseases, including colon cancer. By engineering a Saccharomyces cerevisiae strain, we previously produced two novel phenolic compounds, N-(E)-p-coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, YAvnI) and N-(E)-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, YAvnII), which are endowed with a structural similarity to bioactive oat avenanthramides and stronger antioxidant properties. In this study, we evaluated the ability of these yeast-derived recombinant avenanthramides to inhibit major hallmarks of colon cancer cells, including sustained proliferation, migration and epithelial-mesenchymal transition (EMT). Using the human colon adenocarcinoma cell line HT29, we compared the impact of YAvns and natural Avns, including Avn-A and Avn-C, on colon cancer cells by performing MTT, clonogenic, adhesion, migration, and anchorage-independent growth assays, and analyzing the expression of EMT markers. We found that both YAvns and Avns were able to inhibit colon cancer cell growth by increasing the expression of p21, p27 and p53 proteins. However, YAvns resulted more effective than natural compounds in inhibiting cancer cell migration and reverting major molecular features of the EMT process, including the down-regulation of E-cadherin mRNA and protein levels.

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.

Food allergies can cause intestinal damage that can exacerbate allergic symptoms, and gut microbiota have been shown to influence allergic development. This study was intended to investigate the effects of Avenanthramide (AVA) on colonic damage induced by food allergy and its mechanism. In Exp. 1, AVA administrations alleviated colonic inflammation in mice challenged with ovalbumin, as shown by decreased concentrations of TNF-α, IL-25 and IL-33. Additionally, the AVA supplementations improved intestinal barrier damage by elevating occludin, ZO-1 and claudin-1 levels. Moreover, AVA inhibited NF-κB phosphorylation and enhanced heat shock protein 70 (Hsp70) expression in the colon. In Exp. 2, apoptozole as a Hsp70 inhibitor was used to explore the Hsp70-NF-κB signaling contribution to AVA function. The AVA additions increased the productions of acetate and butyrate, but decreased propionate. Notably, AVA reduced the colonic abundance of propionate-producing microbes such as Muribaculaceae, but elevated butyrate-producing microbes including Roseburia, Blautia, and Lachnospiraceae_NK4A136_group. Microbial alteration could be responsible for the increased butyrate, and thus the up-regulated Hsp70. However, apoptozole treatment eliminated the effects of AVA. Our study revealed that AVA improved colonic injury and inflammation induced by food allergies, and this mechanism may be mediated by the increased microbial-derived butyrate and involved in the Hsp70-NF-κB signaling.

Avenanthramides are a group of N-cinnamoylanthranilic acids (phenolic alkaloid compounds) that are produced in oat plants as phytoalexins, in response to pathogen attack and elicitation. The enzyme catalysing the cinnamamide-generating reaction is hydroxycinnamoyl-CoA: hydroxyanthranilate N-hydroxycinnamoyltransferase (HHT, a member of the super family of BAHD acyltransferases). HHT from oat appears to have a narrow range of substrate usage, with preferred use of 5-hydroxyanthranilic acid (and to a lesser extent, other hydroxylated and methoxylated derivatives) as acceptor molecules, but is able to use both substituted cinnamoyl-CoA and avenalumoyl-CoA thioesters as donor molecules. Avenanthramides thus combine carbon skeletons from both the stress-inducible shikimic acid and phenylpropanoid pathways. These features contribute to the chemical characteristics of avenanthramides as multifunctional plant defence compounds, as antimicrobial agents and anti-oxidants. Although avenanthramides are naturally and uniquely synthesised in oat plants, these molecules also exhibit medicinal and pharmaceutical uses important for human health, prompting research into utilisation of biotechnology to enhance agriculture and value-added production.

Phenol amides are bioactive compounds naturally present in many plants. This class of compounds is known for antioxidant, anti-inflammatory, and anticancer activities. To better understand the reactivity and structure–bioactivity relationships of phenol amides, a large set of structurally diverse pure compounds are needed, however purification from plants is inefficient and laborious. Existing syntheses require multiple steps, including protection of functional groups and are generally overly complicated and only suitable for specific combinations of hydroxycinnamic acid and amine. Thus, to facilitate further studies on these promising compounds, we aimed to develop a facile general synthetic route to obtain phenol amides with a wide structural diversity. The result is a protocol for straightforward one-pot synthesis of phenol amides at room temperature within 25 h using equimolar amounts of N,N′-dicyclohexylcarbodiimide (DCC), amine, hydroxycinnamic acid, and sodium bicarbonate in aqueous acetone. Eight structurally diverse phenol amides were synthesized and fully chemically characterized. The facile synthetic route described in this work is suitable for a wide variety of biologically relevant phenol amides, consisting of different hydroxycinnamic acid subunits (coumaric acid, ferulic acid, and sinapic acid) and amine subunits (agmatine, anthranilic acid, putrescine, serotonin, tyramine, and tryptamine) with yields ranging between 14% and 24%.

The present study aimed to standardize germinated oat extracts (GOEs) by profiling avenanthramides (AVNs) and phenolic acids and evaluate their neuroprotective effects against Aβ1-42-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells. GOEs were standardized to contain 1652.56 ± 3.37 µg/g dry weight (dw) of total AVNs, including 468.52 ± 17.69 µg/g AVN A, 390.33 ± 10.26 µg/g AVN B, and 641.22 ± 13.89 µg/g AVN C, along with 490.03 ± 7.83 µg/g dw of ferulic acid, using a validated analytical method. Treatment with AVN C and GOEs significantly inhibited Aβ1-42-induced cytotoxicity (p < 0.05). Furthermore, both AVNs and GOEs markedly reduced Aβ1-42-induced reactive oxygen species (ROS) generation in SH-SY5Y cells, showing significant scavenging activity at concentrations of 25 μg/mL (AVNs) and 50 μg/mL (GOEs) (p < 0.05). RT-PCR analysis revealed that AVNs and GOEs effectively downregulated the expression of inflammation- and apoptosis-related genes triggered by Aβ1-42 exposure. These findings suggest that GOEs rich in AVNs may serve as a potential functional ingredient for enhancing memory function through the inhibition of neuroinflammation and oxidative stress.

The purpose of our study was to evaluate the potential of solid-state yeast fermentation (SSYF) in improving the phenolic acid content and composition, and the antioxidant activity of commercial wheat bran (WB) and oat bran (OB). The ultrasound-assisted methanolic extracts were compared for their total phenolic content (TPC), phenolics composition, and in vitro antioxidant activity in order to study the effect of fermentation time on the chemical profile and activity of bioactive compounds. The comparative analysis revealed significant differences (p < 0.05) between days of fermentation (0 through 6). The highest TPCs were obtained on day 3 for WB (0.84 ± 0.05 mg of gallic acid equivalents [GAE]/g dry weight [DW]), and on day 4 for OB (0.45 ± 0.02 mg GAE/g DW). The highest relative percentage increase in the phenolics concentration of WB was also registered on day 3 (ferulic acid +56.6%, vanillic acid +259.3%, dihydroxybenzoic acids +161.2%, apigenin-glucoside +15.3%); for OB, this was observed on day 4 (avenanthramide 2f +48.5%, ferulic acid +21.2%). Enhanced antioxidant activities were significantly correlated with the highest TPCs. Our results suggest that SSYF may be a useful procedure for enrichment of antioxidants in cereal bran, considering the design of different functional foods and nutraceuticals.