Introduction

Oats have long been used in the care of dry, sensitive, and itch-prone skin. In addition to starch, β-glucan, lipids, proteins, and other components, oats contain a group of low-abundance but clearly bioactive small molecules known as avenanthramides, which are also commonly referred to as “oat alkaloids” in the skin-care ingredient market.

Avenanthramides are naturally occurring secondary metabolites involved in the defense system of oats. Their biosynthesis increases when oat leaves are exposed to pathogen infection or elicitor stimulation, while multiple avenanthramides are also naturally present in oat grains.[1] In skin research, naturally occurring avenanthramides have been found to affect inflammatory signaling in keratinocytes and mast cell degranulation; studies of the synthetic analog dihydroavenanthramide D and whole oat extracts have also involved certain neuroimmune processes related to pruritus.[2-5]

Another noteworthy chemical feature of avenanthramides is the strong structural similarity of their core scaffold to the antiallergic drug tranilast. Both classes of compounds possess an N-cinnamoylanthranilic acid-type structure, but differ in the hydroxy and methoxy substituents on their aromatic rings, resulting in differences in physicochemical properties and pharmacological activities.

1. What Are Avenanthramides and Where Do They Come From?

Avenanthramides are a group of phenolic amides belonging to the N-cinnamoylanthranilic acid class. Dozens of related structures have been identified in oats, among which avenanthramides A, B, and C have been studied most extensively.

All three contain a 5-hydroxyanthranilic acid moiety and differ mainly in the hydroxycinnamic acid structure at the other end:

① Avenanthramide A contains a p-coumaric acid moiety;

② Avenanthramide B contains a ferulic acid moiety;

③ Avenanthramide C contains a caffeic acid moiety.

A 2019 biosynthetic study further clarified the relationship among the three major avenanthramides. Relevant acyltransferases in oats use 5-hydroxyanthranilic acid together with p-coumaroyl-CoA or caffeoyl-CoA to form avenanthramides A and C; avenanthramide C can subsequently undergo methylation to form avenanthramide B.[1]

The biosynthetic relationships among the three major avenanthramides are shown in Figure 1.

Figure 1. Biosynthetic pathways of the three major oat avenanthramides A, B, and C. Avn-A, Avn-B, and Avn-C represent avenanthramides A, B, and C, respectively; PAL: phenylalanine ammonia-lyase; C4H: cinnamate 4-hydroxylase; 4CL: 4-coumarate-CoA ligase; HHT: hydroxycinnamoyl-CoA:hydroxyanthranilate N-hydroxycinnamoyltransferase; CCoAOMT: caffeoyl-CoA O-methyltransferase; C3′H+: p-coumaroyl-CoA ester 3′-hydroxylase and other related steps. Source: Li et al., 2019, Figure 5.[1] Used under the CC BY 4.0 license.

Avenanthramides are closely associated with plant defense. Early phytochemical studies found that avenanthramide accumulation increases in oat leaves following fungal infection and various elicitor treatments, and these compounds are therefore classified as part of the phytoalexin system of oats. Naturally occurring avenanthramides are also present in oat grains and hulls.[1]

Synthetic molecules structurally related to natural avenanthramides are also used in skin-care applications. One commonly used example is Hydroxyphenyl Propamidobenzoic Acid (HPPBA), also known as dihydroavenanthramide D. It is a synthetic structural analog of avenanthramides rather than avenanthramide A, B, or C directly isolated from oats. The U.S. Food and Drug Administration Global Substance Registration System also lists dihydroavenanthramide D as a synonym for this substance.[16]

2. How Do Skin Inflammation and Pruritus Develop?

In skin care, the term “anti-sensitivity” is often used broadly to describe skin-soothing effects, but skin redness, stinging, and pruritus do not arise from a single mechanism. The cells and signaling processes most closely related to avenanthramide research include keratinocytes, mast cells, and sensory nerves.

Keratinocytes constitute the majority of the epidermis and are also important participants in cutaneous immunity. When exposed to inflammatory stimuli, they can activate intracellular inflammatory signaling and produce interleukins and other inflammatory mediators.

Mast cells are widely distributed throughout the skin. In classic allergic reactions, immunoglobulin E (IgE)-related signaling can activate mast cells, induce changes in intracellular calcium and degranulation, and subsequently trigger the release of histamine and multiple inflammatory mediators.

Cutaneous sensory nerves are also interconnected with these immune processes. Histamine and neuropeptides such as substance P can participate in pruritic signaling, while persistent scratching can further damage the skin barrier, creating a mutually reinforcing cycle of inflammation and pruritus.

3. How Do Avenanthramides Affect Inflammation- and Pruritus-Related Signaling?

3.1 Avenanthramides Inhibit NF-κB Inflammatory Signaling in Keratinocytes

A 2008 study investigated the effects of avenanthramides on inflammatory signaling in the skin.

Nuclear factor kappa B (NF-κB) is an important transcription factor that regulates numerous inflammation-related genes. When keratinocytes are exposed to inflammatory stimuli such as tumor necrosis factor-α, the NF-κB pathway is activated, promoting the expression of downstream inflammatory mediators.

The study found that avenanthramides inhibited degradation of the NF-κB inhibitory protein IκB-α, reduced phosphorylation of the NF-κB p65 subunit, and decreased tumor necrosis factor-α-induced NF-κB activity and interleukin-8 release. In mouse experiments, topical application of avenanthramides also reduced contact inflammation, neurogenic inflammation, and scratching behavior induced by pruritogenic stimulation.[2]

These findings indicate that avenanthramides can reduce the amplification of inflammatory responses in keratinocytes and provide cellular and animal experimental evidence for anti-inflammatory and anti-pruritic effects.

3.2 Avenanthramide C Inhibits IgE-Mediated Mast Cell Degranulation and Histamine Release

Mast cells represent another important component of avenanthramide research.

A 2019 study examined avenanthramide C obtained from germinated oats using rat basophilic leukemia cells, mouse bone marrow-derived mast cells, and rat peritoneal mast cells.

Avenanthramide C inhibited mast cell degranulation following immunoglobulin E stimulation and reduced histamine release. Further analysis showed that multiple signaling events downstream of the high-affinity immunoglobulin E receptor, as well as the increase in intracellular calcium, were affected, accompanied by decreases in the expression and release of inflammatory cytokines.[3]

The study also used mouse models of systemic allergic reactions and passive cutaneous allergic reactions, in which avenanthramide C reduced several indicators of allergic responses. These findings provide preclinical evidence that avenanthramide C can modulate mast cell-mediated inflammation.[3]

The stage of action demonstrated in this study differs from that of classical histamine H1 receptor antagonists. H1 receptor antagonists primarily block the effects produced when already-released histamine binds to its receptor, whereas the avenanthramide C study involved mast cell activation, degranulation, and the process of histamine release itself.

3.3 Dihydroavenanthramide D Affects Substance P–Neurokinin-1 Receptor-Related Processes

Some forms of pruritus are not primarily driven by histamine. Signaling involving the neuropeptide substance P and the neurokinin-1 receptor (NK1R) represents an important pathway in research on neuroimmune pruritus.

A 2017 study showed that the synthetic analog dihydroavenanthramide D could interact with the neurokinin-1 receptor and inhibit mast cell degranulation and interleukin-6 release. Based on these findings, the authors proposed that dihydroavenanthramide D may exert an inhibitory effect on the neurokinin-1 receptor.[4]

3.4 Oat Kernel Extract Can Modulate MRGPRX2-Mediated Mast Cell Activation

A study published online in December 2025 and included in a 2026 journal issue extended the connection between oats and mast cells to Mas-related G protein-coupled receptor X2 (MRGPRX2).

MRGPRX2 is expressed on human skin mast cells and can be activated by substance P, certain drugs, and multiple other ligands. Activation of this receptor can trigger mast cell degranulation and participate in processes related to inflammation, pain, and pruritus.

Using a human mast cell line and primary human mast cells, the study found that a natural oat kernel extract reduced mast cell degranulation induced by three MRGPRX2 agonists and decreased the release of β-hexosaminidase and tryptase, as well as related indicators of cellular activation.[5]

The experimental material in this study was a whole oat kernel extract rather than purified avenanthramide A, B, or C. Therefore, the study supports the ability of oat extract to modulate MRGPRX2-mediated mast cell activation, but does not establish that any individual avenanthramide is a direct ligand or specific inhibitor of MRGPRX2.

4. Structural Similarity Between Avenanthramides and Tranilast

Avenanthramides show clear structural similarity to the antiallergic drug tranilast.

The comparison between avenanthramide B and tranilast is particularly straightforward.

Avenanthramide B contains:

5-Hydroxyanthranilic acid

—amide bond—

4-Hydroxy-3-methoxycinnamoyl group

Tranilast contains:

Anthranilic acid

—amide bond—

3,4-Dimethoxycinnamoyl group

Both molecules contain two aromatic rings, an amide linkage, a carboxylic acid group, and a conjugated double bond within the cinnamoyl moiety, making them structurally closely related N-cinnamoylanthranilic acid derivatives.

Their principal differences lie in the substituents on the aromatic rings: the anthranilic acid ring of avenanthramide B contains an additional hydroxy group, while the aromatic ring of its cinnamic acid-derived portion contains one hydroxy group and one methoxy group; the corresponding positions in tranilast contain two methoxy groups.

Although these changes involve only a small number of substituents, they can alter the distribution of hydrogen-bond donors and acceptors, polarity, lipophilicity, and the manner in which the molecule interacts with protein binding sites.

4.1 Similar Scaffolds Are Associated with Partial Functional Overlap, but Their Pharmacological Profiles Are Not Identical

Classical studies of tranilast have shown that it can inhibit immunoglobulin E-mediated histamine release from mast cells and affect calcium influx in mast cells, among other processes.[6]

This shows a degree of functional overlap with the experimentally observed inhibition of mast cell degranulation and histamine release by avenanthramide C.

Tranilast also has other pharmacological effects. For example, in studies using fibroblasts derived from human keloids and hypertrophic scars, tranilast inhibited transforming growth factor-β1 release and collagen synthesis, forming part of the evidence base for its antifibrotic activity.[7]

Clear structure–activity differences also exist within the avenanthramide family. A 2020 in vitro lipoxygenase study compared 12 avenanthramide structures, the corresponding hydroxycinnamic acids, and tranilast. Some compounds containing caffeic acid- or sinapic acid-type structures showed relatively pronounced lipoxygenase inhibition; some of the sinapic acid-type structures used in the study were synthetic compounds included for structure–activity comparisons. Avenanthramides containing p-coumaric acid- or ferulic acid-type structures showed weaker or no obvious inhibition. Under the same experimental conditions, tranilast also did not show corresponding lipoxygenase inhibition.[8]

These results indicate that similarity in the core scaffold may be accompanied by overlap in certain biological effects, while peripheral substituents can still substantially alter the specific activity profile.

5. Avenanthramides and Glucocorticoids Differ in Mechanism of Action and Level of Evidence

Glucocorticoids exert their effects through intracellular glucocorticoid receptors. Following receptor activation, they participate in broad regulation of gene transcription and affect multiple inflammatory pathways, including NF-κB and activator protein 1, thereby producing potent anti-inflammatory and immunomodulatory effects.

There are also clear differences in clinical evidence. The American Academy of Dermatology guideline for topical treatment of atopic dermatitis in adults recommends topical glucocorticoids and also recommends moisturizers, topical calcineurin inhibitors, topical phosphodiesterase 4 inhibitors, and topical Janus kinase inhibitors.[9]

Evidence for avenanthramides is derived primarily from keratinocyte, mast cell, and animal models, whereas human studies involving oats more often evaluate colloidal oatmeal or complete formulations. Human clinical evidence for individual purified avenanthramide A, B, or C as therapeutic agents for inflammatory skin diseases remains limited.

6. What Oat-Derived Soothing Ingredients Are Used in the Skin-Care Market?

6.1 Colloidal Oatmeal: Regulatory Use and Human Studies

Colloidal oatmeal is a complex natural ingredient produced by processing oats into fine particles. It contains starch, β-glucan, proteins, lipids, and various phenolic compounds. Starch and β-glucan contribute to film formation and moisture retention, while phenolic compounds such as avenanthramides are associated with its anti-inflammatory and soothing effects.[15]

The U.S. Food and Drug Administration Over-the-Counter Monograph M016 lists colloidal oatmeal as an active skin protectant ingredient, with a minimum concentration of 0.007% when used alone; when used in combination with mineral oil as specified in the monograph, the minimum concentration of colloidal oatmeal may be 0.003%. In compliant topical formulations, colloidal oatmeal may be used to temporarily protect irritated skin and help relieve minor skin irritation and itching.[10]

Human studies have also focused mainly on complete colloidal oatmeal formulations. For example, a 2017 randomized, double-blind, active-controlled study involving 90 children with mild-to-moderate atopic dermatitis compared a 1% colloidal oatmeal cream with a prescription barrier cream. After three weeks, the colloidal oatmeal group met the prespecified noninferiority criterion for change in Eczema Area and Severity Index, and both groups showed improvements in overall dermatitis and pruritus scores.[11]

These clinical studies evaluate complete formulations. Colloidal oatmeal contains multiple components with moisturizing, barrier-protective, and soothing effects; therefore, the clinical efficacy of the complete formulation cannot be attributed solely to avenanthramides.

6.2 Oat Extracts: Bioactive Composition Depends on Raw Materials and Extraction Conditions

Oat extracts are widely used in creams, lotions, serums, cleansers, and body-care products.

Oat cultivar, growing environment, and germination status can influence the levels of avenanthramides and other phenolic compounds in the raw material. Extraction solvent and solvent concentration, solid-to-liquid ratio, extraction time, temperature, and number of extraction cycles can also influence avenanthramide extraction. Consequently, different oat extracts may vary in avenanthramide content and overall bioactive composition.[12,13,17]

When avenanthramides are used as target bioactive components, the levels of characteristic compounds such as avenanthramides A, B, and C can be measured to control and standardize extract composition, thereby providing more clearly defined bioactive compound levels across different batches of raw material.[17]

6.3 Synthetic Avenanthramide Analog: Dihydroavenanthramide D

Hydroxyphenyl Propamidobenzoic Acid, also known as dihydroavenanthramide D, is a structurally defined synthetic avenanthramide analog and differs from natural avenanthramides A, B, and C as well as from multicomponent oat extracts. Related studies have examined mast cell degranulation and substance P–neurokinin-1 receptor-related inflammatory and pruritic processes.[4]

7. Research and Application Boundaries of Avenanthramides

7.1 Natural Avenanthramide Content and Composition Vary

Avenanthramide content in oats can be affected by cultivar, growing environment, germination conditions, and other factors.

A 2022 study analyzed multiple Canadian oat cultivars grown at different locations and found that environmental factors significantly affected avenanthramide concentrations, while genotype and environment jointly influenced the composition of different phenolic compounds.[12]

A 2024 study further analyzed changes in avenanthramides in 12 oat cultivars over different germination periods. Total avenanthramide levels were, on average, relatively high after 48–72 hours of germination, with some cultivars reaching approximately 1–1.2 mg/g.[13]

The compositional consistency and content control of natural avenanthramide raw materials are therefore influenced by oat cultivar, cultivation conditions, germination treatment, and subsequent extraction and standardization processes.

7.2 Human Evidence for Individual Avenanthramides Remains Limited

Avenanthramides have accumulated a substantial body of cell and animal research, including studies of their effects on inflammatory signaling, mast cell degranulation, and histamine release.

Human studies, however, have focused mainly on colloidal oatmeal or complete formulations containing oat-derived ingredients. Human topical studies of individual avenanthramide A, B, or C remain limited, and their effective topical concentrations, local skin exposure, and clinical effects under different inflammatory and pruritic conditions require further clarification.

Current evidence supports anti-inflammatory, soothing, and anti-pruritic-related biological effects of avenanthramides, but the clinical application of individual avenanthramides still requires further support from human studies.

7.3 Overall Tolerability Is Favorable, but Individual Sensitization Risk Should Still Be Considered

Personal-care products containing colloidal oatmeal have generally shown low irritation and sensitization potential in human evaluations, although studies have reported sensitization to oat proteins in some children with atopic dermatitis. These findings involve oat proteins or whole oat-derived materials and cannot be directly attributed to avenanthramide A, B, or C.[15]

The synthetic avenanthramide analog Hydroxyphenyl Propamidobenzoic Acid may also show individual sensitization potential. A 2023 case report described allergic contact dermatitis following use of a skin-soothing product containing this ingredient, and patch-test findings supported an association between Hydroxyphenyl Propamidobenzoic Acid and the allergic reaction.[14]

The tolerability and sensitization risk of oat-derived soothing ingredients therefore need to be evaluated in the context of the specific ingredient, use concentration, formulation composition, and target population.

8. Representative Chemicals Related to the Structure and Biosynthesis of Avenanthramides and to Research on Skin Inflammation and Pruritus Mechanisms

Table 1. Avenanthramides, Structural Units, and Related Molecules

Table 2. Reference Compounds for Mast Cell, Pruritic Signaling, and Glucocorticoid Studies

Note: The products listed above are representative Aladdin research products. Specific applications should be determined according to product specifications, batch-specific COAs, and the intended reaction or evaluation system. Additional product specifications, grades, and COA information can be retrieved from the Aladdin website using the product name, CAS number, or catalog number.

References

[1] Li Z, Chen Y, Meesapyodsuk D, Qiu X. The Biosynthetic Pathway of Major Avenanthramides in Oat. Metabolites. 2019;9(8):163. DOI: 10.3390/metabo9080163.

[2] Sur R, Nigam A, Grote D, Liebel F, Southall MD. Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity. Archives of Dermatological Research. 2008;300(10):569–574. DOI: 10.1007/s00403-008-0858-x.

[3] Dhakal H, Yang EJ, Lee S, et al. Avenanthramide C from germinated oats exhibits anti-allergic inflammatory effects in mast cells. Scientific Reports. 2019;9:6884. DOI: 10.1038/s41598-019-43412-2.

[4] Lotts T, Agelopoulos K, Phan NQ, et al. Dihydroavenanthramide D inhibits mast cell degranulation and exhibits anti-inflammatory effects through the activation of neurokinin-1 receptor. Experimental Dermatology. 2017;26(8):739–742. DOI: 10.1111/exd.13265.

[5] Kaesler S, Argiriu D, Kandage SM, et al. Modulation of Mast Cell Activation via MRGPRX2 by Natural Oat Extract. International Journal of Molecular Sciences. 2026;27(1):334. DOI: 10.3390/ijms27010334.

[6] Koda A, Kurashina Y, Nakazawa M. The inhibition mechanism of histamine release by N-(3,4-dimethoxycinnamoyl) anthranilic acid. International Archives of Allergy and Applied Immunology. 1985;77(1–2):244–245. DOI: 10.1159/000233800.

[7] Suzawa H, Kikuchi S, Arai N, Koda A. The mechanism involved in the inhibitory action of tranilast on collagen biosynthesis of keloid fibroblasts. Japanese Journal of Pharmacology. 1992;60(2):91–96. DOI: 10.1254/jjp.60.91.

[8] Landberg R, Sunnerheim K, Dimberg LH. Avenanthramides as lipoxygenase inhibitors. Heliyon. 2020;6(6):e04304. DOI: 10.1016/j.heliyon.2020.e04304.

[9] Sidbury R, Alikhan A, Bercovitch L, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. Journal of the American Academy of Dermatology. 2023;89(1):e1–e20. DOI: 10.1016/j.jaad.2022.12.029.

[10] U.S. Food and Drug Administration. Over-the-Counter Monograph M016: Skin Protectant Drug Products for Over-the-Counter Human Use. Final Administrative Order OTC000005. 2021.

[11] Lisante TA, Nuñez C, Zhang P. Efficacy and safety of an over-the-counter 1% colloidal oatmeal cream in the management of mild to moderate atopic dermatitis in children: a double-blind, randomized, active-controlled study. Journal of Dermatological Treatment. 2017;28(7):659–667. DOI: 10.1080/09546634.2017.1303569.

[12] Malunga LN, Ames N, Mitchell Fetch J, Netticadan T, Thandapilly SJ. Genotypic and environmental variations in phenolic acid and avenanthramide content of Canadian oat (Avena sativa). Food Chemistry. 2022;388:132904. DOI: 10.1016/j.foodchem.2022.132904.

[13] Jágr M, Hofinger-Horvath A, Ergang P, et al. Comprehensive study of the effect of oat grain germination on the content of avenanthramides. Food Chemistry. 2024;437(Pt 1):137807. DOI: 10.1016/j.foodchem.2023.137807.

[14] Blanchard G, Walker A, Dendooven E, et al. Allergic contact dermatitis from a skin-calming cream containing hydroxyphenyl propamidobenzoic acid. Contact Dermatitis. 2023;88(1):68–70. DOI: 10.1111/cod.14221.

[15] Criquet M, Roure R, Dayan L, Nollent V, Bertin C. Safety and efficacy of personal care products containing colloidal oatmeal. Clinical, Cosmetic and Investigational Dermatology. 2012;5:183–193. DOI: 10.2147/CCID.S31375.

[16] U.S. Food and Drug Administration. Global Substance Registration System: Hydroxyphenyl Propamidobenzoic Acid, UNII 25KRT26H77.

[17] Woolman M, Liu K. Simplified Analysis and Expanded Profiles of Avenanthramides in Oat Grains. Foods. 2022;11(4):560. DOI: 10.3390/foods11040560.

For more related articles, see below:

The Moisturizing and Low-Moisture Protective Mechanisms of Trehalose: From Its α,α-1,1 Structure and Hydration Dynamics to In Vitro Skin Barrier Research

Scientific Rationale and Application Assessment of Olive Leaf Extract in Skin Redness Care

How Do Collagen Peptides Act on the Skin? From Surface Hydration and Percutaneous Delivery to Fibroblasts and Collagen Homeostasis

Probiotics, Prebiotics, and Postbiotics in Skin Care: Conceptual Distinctions, Mechanisms of Action, and Their Applications in the Care of Dry, Itchy, and Rough Skin

Moisturizing Mechanism of Polyglutamic Acid: From the γ-Glutamyl Structure to Hydration Networks and Surface Film-Forming Behavior

Molecular Structure, Photochemical Behavior, and Role of Octocrylene in Sunscreen Formulations

Analysis of Hydrolyzed Pearl as a Cosmetic Raw Material: Preparation Process, Active Components, and Skincare Formulation Applications

The Dual-Targeted Skin-Brightening Mechanism of 4-MSK: Inhibiting Melanin Production and Reducing Epidermal Pigment Retention

Antioxidant Mechanisms, Stability, and Delivery Strategies of Resveratrol in Skincare Research

Antioxidant Mechanisms of Ferulic Acid in Skincare, Vitamin C/E Synergy, and Stable Delivery Applications

Tocopherols in the Vitamin E Family: How They Block the Chain Reaction of Lipid Peroxidation in Skin Lipids

The Skin Anti-Aging Mechanisms of α-Lipoic Acid: ALA/DHLA Redox Cycling, the Antioxidant Network, and Regulation of Collagen AGE Formation

Mechanistic Analysis of Topical Glutathione in Skincare: Cellular Redox Regulation, Skin Delivery Challenges, and SLN-Based Delivery Strategies

Mechanism of Kojic Acid in Reducing Hyperpigmentation: From Tyrosinase Inhibition to Melanin Production Regulation

Beneath the Skin: Protein- and Peptide-Based Actives in Skincare and Aesthetic Medicine

Understanding Ceramides from the Perspective of the Stratum Corneum Lipid Barrier: Moisturizing and Barrier-Repair Mechanisms, Ingredient Selection, and Formulation Research Considerations

Hyaluronidase: Unlocking a “Magic Enzyme” in Biomedicine

Hyaluronan

Recombinant Humanized Type III Collagen: Structural Basis, Manufacturing Technologies, and Dermatological Applications

Trehalose: Physicochemical Characteristics, Manufacturing Processes, and Application Guidelines