5. Biological activities of AGPs

Phytopharmaceuticals used for immunostimulation play an important role in selfmedication. Since many years, scientists are looking for the active compounds of these preparations. For Echinacea, important compounds are low molecular weight alkamides and high molecular weight polysaccharides and glycoproteins, especially AGPs. In vitro we could show that AGPs bind to human leukocytes and stimulate release of cytokines from murine macrophages. Investigations of Prof. Dr. S. Alban (Institute of Pharmacy, CAU Kiel) proved activation of human complement system by AGPs from Echinacea purpurea in vitro.

scematic binding to leucocyte
Binding of AGPs to human leukocytes (determination of fluorescence intensity by FACS)

 

Selected publications

Schöll-Naderer M, Helm O, Spencker J, Pfeifer L, Rätsch T, Sebens S, Classen B: Plant-derived saccharides and their inhibitory potential on metastasis associated cellular processes of pancreatic ductal adenocarcinoma cells. Carbohydrate Research (2020) 490: 107903.

Peters M, Guidato PM, Peters K, Megger DA, Sitek B, Classen B , Heise EM, Bufe A: Allergy-protective arabinogalactan modulates human dendritic cells via c-type-lectins and inhibition of NFκB. J Immunology (2015) 196(4):1626-35.

Classen B, Thude S, Blaschek W, Wack M, Bodinet C: Immunomodulatory effects of arabinogalactan-proteins from Baptisia and Echinacea. Phytomedicine (2006) 13: 688-694.

Thude S, Classen B, Blaschek W, Barz D, Thude D: Binding studies of an arabinogalactan-protein from Echinacea purpurea to leucocytes. Phytomedicine (2006) 13: 425-427.

Alban S, Classen B, Brunner G, Blaschek W: Haemolytic complement assay for the differentiation between the complement modulating effects of an arabinogalactan-protein from Echinacea purpurea and heparin. Planta Med (2002) 68: 1118-1124.

 

The question arises, how high molecular weight glycans might interact with the human immune system when taken orally. Oral uptake of AGPs may be possible at the Peyer´s patches in the small intestine. In first experiments, Peyer´s patches from different species (mouse, rabbit, human) were prepared (see Fig.) and binding of AGPs in this area was investigated by immunofluorescence.

ileum section
Cross section of human ileum

 

A further possibility of interaction are special human receptors called galectins, which are also present in the intestinal mucosa. These galectins are characterized by their affinity to bind ß-galactose residues, and therefore binding of plant galactans to these receptors might be possible. For degraded citrus pectin, interaction with galectin 3 has already been proven by different working groups. Our first experiments by ELISA revealed weak binding of degraded, galactose-rich AGP from Echinacea to galectin 3. Influence of galectins on tumor progression has been described by several authors and therefore galectins are considered as target proteins for cancer treatment. In a cooperation with Prof. S. Sebens (Institut für experimentelle Tumorforschung, CAU Kiel) first experiments revealed, that adhesion of pancreatic cancer cells, which express galectin 3 on their surface, to human liver cells is reduced by addition of degraded plant galactans.