Proteomic response to 2-HOBA supports a possible role in the prevention of inflammatory disease

Background

Inflammation is associated with the formation of reactive oxygen species (ROS) and the formation of lipid-derived compounds, such as isolevuglandins (IsoLGs). In a study from MTI Biotech inc., the Olink® Target 96 Inflammation panel was used  during a clinical trial to measure protein biomarker responses in healthy subjects administered with the IsoLG inhibitor, 2-Hydroxybenzylamine (2-HOBA). This natural compound, derived from buckwheat seeds, reacts with IsoLG adducts to prevent adduct formation with proteins and DNA and is therefore well positioned as an agent for the prevention of inflammatory-prone diseases.

Outcome

Comparing samples taken before and after an oral 15-day treatment regimen with 2-HOBA, significant changes were seen in the relative plasma concentration of 15 immune proteins. Levels of CCL19, IL-12β, IL-20Rα, and TNFβ, were most significantly increased, whereas levels of TWEAK were significantly decreased – these proteins may reflect the in vivo immune targets of 2-HOBA. Pathway analysis of the key proteins identified implicated biological processes related to the recruitment, attraction, and movement of different immune cell types.

The proteins identified in the study may be responsible for the protective effects of 2-HOBA against reactive electrophiles, such as IsoLGs. As these are commonly expressed in conditions of excessive oxidative stress, 2-HOBA could have a role as a IsoLG scavenger to proactively improve immune health in a variety of inflammation-prone diseases and conditions.

Rathmacher-et-al-2023

Citation

Rathmacher JA, Fuller JC, Abumrad NN, et al. Inflammation Biomarker Response to Oral 2-Hydroxybenzylamine (2-HOBA) Acetate in Healthy Humans. (2023) Inflammation, DOI: 10.1007/s10753-023-01801-w

the use of 2-HOBA in two cohorts of healthy adult humans, young and elderly, appears to favorably alter a panel of inflammation protein biomarkers, specifically, CCL19, IL-12B, IL-20RA, TNFB, and TWEAK, and these may be responsible for the protective effects of 2-HOBA against reactive electrophiles

Rathmacher et al. (2022)

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