Identification of chlorophyll a-b binding protein AB96 as a novel TGF\u03b21 neutralizing agent

Fabio Grundland Freile,Steven Lynham,Timothy N C Wells,Natasha M Puri,Nicola O’Reilly,Merlin Willcox,Graham H Mitchell,Richard Beatson

doi:10.1038/s41598-021-87454-x

Fabio Grundland Freile, Steven Lynham + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-87454-x

Copy DOI

Abstract

The discovery of compounds and proteins from plants has greatly contributed to modern medicine. Vernonia amygdalina Del. (Compositae) is used by humans and primates for a variety of conditions including parasitic infection. This paper describes the serendipitous discovery that V. amygdalina extract was able to bind to, and functionally inhibit, active TGFβ1. The binding agent was isolated and identified as chlorophyll a-b binding protein AB96. Given that active TGFβ1 contributes to the pathology of many infectious diseases, inhibiting these processes may explain some of the benefits associated with the ingestion of this species. This is the first plant-derived cytokine-neutralizing protein to be described and paves the way for further such discoveries.

Highlights

Vernonia amygdalina Del. (Compositae) (VA) is used by humans and other primates as a natural remedy for a variety of pathologies, including plasmodium and helminth infections[1–3]
Mo-DCs were incubated with VA(aq) for 24 h after which they were assessed for changes in cell surface proteins and cytokine secretion
Our initial hypothesis was that this indicated a specific inhibition of TGFβ1 production, when exogenous active TGFβ1 was added to the system, we saw the same reduction

Summary

Introduction

Vernonia amygdalina Del. (Compositae) (VA) is used by humans and other primates as a natural remedy for a variety of pathologies, including plasmodium and helminth infections[1–3]. In its active form it can (a) induce regulatory T-cells (Tregs) which suppress the function of other immune cells to limit the immune response, (b) induce class switching of B cells from IgG to IgA producers, with IgA inducing less inflammatory responses (c) induce tolerogenic antigen presenting cells, which promote anergy/non-response to antigen and (d) inhibit the polarization of T helper (CD4) cells[12] resulting in an impaired immune response These processes are commonly seen in cancers, TGFβ1 signaling is currently being targeted in > 50 cancer clinical trials through the use of antibodies or specific inhibitors[13]. Beyond immune evasion, through TGFβ1 induction and activation within the host, it has recently been shown that the helminth, Heligmosomoides polygyrus, produces its own functional TGFβ1 m imetic[20], whilst in Schistosoma mansoni, human TGFβ1 directly regulates parasitic gene expression[21], suggesting the critical importance of this pathway for parasitic survival

Methods

Results

Conclusion