Avenanthramides as lipoxygenase inhibitors.

Avenanthramides (AVAs) present in oats are amides of anthranilic and cinnamic acids. AVAs are potent antioxidants and have anti-inflammatory properties. There are various potential mechanisms for their anti-inflammatory effects, including inhibition of lipoxygenases (LOX), which catalyse oxygenation of polyunsaturated fatty acids into potent signal molecules involved in inflammatory processes. In this study, AVAs were screened for LOX inhibition in vitro and structure-activity relationships were examined. Twelve different AVAs at 0.6 mM were tested as LOX inhibitors. The corresponding free cinnamic acids, the AVA analogue Tranilast® and the known LOX inhibitor trans-resveratrol were included for comparison. It was found that AVAs comprising caffeic or sinapic acid exhibited significant lipoxygenase inhibition (60-90%) (P < 0.05), whereas low or no inhibition was observed with AVAs containing p-coumaric or ferulic acid. No difference in inhibition was seen on comparing AVAs with their free corresponding cinnamic acids, which implies that the anthranilic acid part of the avenanthramide molecule does not affect inhibition. Trans-resveratrol showed inhibition, whereas no inhibition was seen for Tranilast® at the concentrations used in this study. This study suggests that aventahtramides comprising caffeic acid or sinapic acid partly exert their antioxidant and anti-inflammatory effects via lipoxygenase inhibition.

In vitro antioxidant activity and antigenotoxic effects of avenanthramides and related compounds.

Avenanthramides are substituted N-cinnamoylanthranilic acids, with hydroxycinnamic acid and anthranilic acid moieties. These alkaloid phenols, which are unique to oats, may confer health benefits via antioxidant or other mechanisms. Synthetic avenanthramides, hydroxycinnamic acids, Tranilast, and ascorbic acid were evaluated for antioxidant activity using two assays, DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant potential), and for antigenotoxicity using the Comet assay with stressed human adenocarcinoma colon cells. Of all the compounds tested, N-(3',4'-dihydroxy-(E)-cinnamoyl)-5-hydroxyanthranilic acid (2c), an abundant oat avenanthramide, generally had the highest activity in all three assays. The drug Tranilast showed antigenotoxic effects, but not antioxidant activity, suggesting that antigenotoxicity is not dependent on antioxidant effects. Overall, results show that avenanthramides exert antioxidant and antigenotoxic activities that are comparable to those of ascorbic acid and which have the potential to exert beneficial physiological effects.

Phytochemical and fiber components in oat varieties in the HEALTHGRAIN Diversity Screen.

The levels and compositions of a range of phytochemicals (sterols, tocols, avenanthramides, folates, phenolic acids) and dietary fiber components were determined in five oat cultivars (four husked and one naked) grown on a single site in 2005. The total levels of tocols, phenolic acids, and avenanthramides varied by over 2-fold between cultivars, but less variation occurred in total sterols and total folates. Limited variation was also observed in the dietary fiber content and composition of the four husked lines. These results indicate that it may be possible to selectively breed for lines with high contents of dietary fiber and specific groups of phytochemicals.

Phenolic compounds in oat grains (Avena sativa L.) grown in conventional and organic systems.

The concentrations of avenanthramides (AVAs), hydroxycinnamic acids (HCAs), a sucrose-linked truxinic acid (TASE), and certain agronomic parameters were analyzed in organically and conventionally grown oats. Three cultivars of oats (i.e. Freja, Sang, and Matilda) were grown according to standards for both conventional and organic farming in Sweden, from 1998 to 2000. Two levels of nitrogen (N) and three replicates were included. Overall, there were significant differences between years, cultivars, and N rate for AVA concentration in the grains, but there were no differences in concentration as a consequence of the conventional or organic cropping system used. The AVA content was higher in the samples grown in 2000, particularly in the cultivar Matilda, and was negatively affected by higher N rates. The HCAs showed cultivar and year differences, but were not influenced by N rates or the cropping system. The HCA content was highest in Matilda, and was significantly lower in samples grown in 1999. The concentration of TASE differed only between years, and was about 100% higher in samples from 1999, compared with samples from 1998 and 2000. The AVA and HCA concentrations were negatively correlated to the yield and specific weight of the grains and positively correlated to the protein content. Conversely, the concentration of TASE was positively correlated to the yield. The specific parameters responsible for the variation in the phenolic compounds are not known, but it seems that factors affecting the yield and/or the specific weight also affect the concentrations of AVAs, HCAs, and TASE in oat grains.

Avenanthramides in oats (Avena sativa L.) and structure-antioxidant activity relationships.

Eight avenanthramides, amides of anthranilic acid (1) and 5-hydroxyanthranilic acid (2), respectively, and the four cinnamic acids p-coumaric (p), caffeic (c), ferulic (f), and sinapic (s) acid, were synthesized for identification in oat extracts and for structure-antioxidant activity studies. Three compounds (2p, 2c, and 2f) were found in oat extracts. As assessed by the reactivity toward 1,1-diphenyl-2-picrylhydrazyl (DPPH), all avenanthramides except 1p showed activity. Initially, the antioxidant activity of the avenanthramides decreased in a similar order as for the corresponding cinnamic acids, that is: sinapic > caffeic > ferulic > p-coumaric acid. The avenanthramides derived from 2 were usually slightly more active than those derived from 1. All avenanthramides inhibited azo-initiated peroxidation of linoleic acid. 1c and 1s were initially the most effective compounds. The relative order of antioxidant activities was slightly different for the DPPH and the linoleic acid assays run in methanol and chlorobenzene, respectively.

Effects of commercial processing on levels of antioxidants in oats (Avena sativa L.).

The effects of various commercial hydrothermal processes (steaming, autoclaving, and drum drying) on levels of selected oat antioxidants were investigated. Steaming and flaking of dehulled oat groats resulted in moderate losses of tocotrienols, caffeic acid, and the avenanthramide Bp (N-(4'-hydroxy)-(E)-cinnamoyl-5-hydroxy-anthranilic acid), while ferulic acid and vanillin increased. The tocopherols and the avenanthramides Bc (N-(3',4'-dihydroxy-(E)-cinnamoyl-5-hydroxy-anthranilic acid) and Bf (N-(4'-hydroxy-3'-methoxy)-(E)-cinnamoyl-5-hydroxy-anthranilic acid) were not affected by steaming. Autoclaving of grains (including the hulls) caused increased levels of all tocopherols and tocotrienols analyzed except beta-tocotrienol, which was not affected. Vanillin and ferulic and p-coumaric acids also increased, whereas the avenanthramides decreased, and caffeic acid was almost completely eliminated. Drum drying of steamed rolled oats resulted in an almost complete loss of tocopherols and tocotrienols, as well as a large decrease in total cinnamic acids and avenanthramides. The same process applied to wholemeal made from groats from autoclaved grains resulted in less pronounced losses, especially for the avenanthramides which were not significantly affected.