Gallo-ellagi-tannins of chamaenerion angustifolium: antitumor activity

1 – Research Institute of Experimental Diagnostics and Tumor Therapy Federal State Budgetary Institution named after N.N. Blokhin, Ministry of Health of Russia, Moscow, 2 - Federal State Budgetary Institution "VILAR", Moscow, Russia

Currently, in Russia and abroad, there is a growing interest in the use of gallo-ellagi-tannins of fireweed (Chamerion angustifolium) as a source of antitumor and immunomodulating agents [1]. Fireweed (Chamerion angustifolium) is a popular tea; it is typical of the flora in many regions of Russia, and therefore studies on its chemical composition and biological activity are relevant.

The aim of our research work was to study the possibility of isolating and using gallo-ellagi-tannins as adjuvant for immunization (obtaining a B-cell response) in an experiment in mice.

Materials and methods . Gallo-ellagi-tannins with antitumor properties (the chanerol substance) were isolated from inflorescences and shoots of Chamerion angustifolium from the Onagraceae family, according to the original method by the N.N. Blokhin Research Institute [2]. We used selective extraction methods and chromatographic techniques for separating the obtained compounds.

To test the possibility of using tannins as an adjuvant, immunization experiments were carried out in 21 mice. For comparison, the following compositions were prepared: a) 25 µg chamenerin I + PRAME, b) 25 µg chamenerin II + PRAME, c) 25 µg chamenerin III + PRAME, d) 25 µg of the sum of higher oligomeric tannins of Chamerion angustifolium + PRAME, e) Al (OH)3 + PRAME used as the positive reference for the conventional adjuvant and the antigen presence f) pure PRAME protein used as the positive reference for the antigen presence, g) the negative reference without immunization. The B-cell response of the compounds was assessed by the intensity of staining of the PRAME-expressing K562 cell line with the sera of the immunized mice.

Results . According to the results of flow cytometry, antibodies contained in the mice sera stained the K562 cells with different intensity. The staining intensity of the K562 cell line was highest when using the sera from the mice immunized with dimeric and trimeric gallo-ellagi-tannins (chamenerin I and chamenerin II). Serum from the mice immunized with chamenerin I stained the cells more intensely than the sera from the reference mice (p = 0.0282). Serum, obtained from the mice immunized with chamenerin II, stained cells more intensely than the reference, but the differences tended to be significant (p = 0.0933). The rest of the data did not significantly affect (p>0.1) the results of the experiment.

Conclusions. Thus, the drug chanerol based on the dimeric tannin derived from the inflorescences and shoots of the fireweed plant (Chamerion angustifolium) contains admixed trimeric and higher oligomeric tannins. An analysis of the biological activity demonstrated that the most pronounced B- cell response in mice against the PRAME protein was achieved with the use of dimeric and trimeric gall-ellagi-tannins as an adjuvant for immunization.

The offered method for isolating the oligomeric hydrolysable macrocyclic tannins allows obtaining purified compounds for preclinical studies in the required quantities.

The researches were carried out within the framework of the state task of the Research Institute EDTT Federal State Budgetary Institution named after N.N. Blokhin and state task of Federal State Budgetary Institution "VILAR" (FGUU-202-0009, FGUU-2022-0010).