Environmental Research, volume 191, pages 110049
Exploring bioactivity potential of polyphenolic water-soluble lignin derivative.
Fedoros E I
1
,
Badun G.A.
,
Baldueva I A
1
,
Perminova I V
,
Chernysheva M G
,
Nekhaeva T L
1
,
Kuznetsova A I
1
,
Ryakhovskiy A A
3
,
Pigarev S E
2
,
Semenov A.L.
1
,
Tyndyk M L
,
Gubareva E. A.
,
Panchenko A. V.
,
Bykov V N
1
,
Anisimov V.N.
,
Grozdova I D
,
Danilova A B
,
Emelyanova N V
1
,
Grozdova Irina D
2
,
Danilova Anna
1
,
Tyndyk Margarita
1
,
Gubareva Ekaterina
1
,
Panchenko Andrey
1
,
3
CHEMDIV LTD, Moscow District, Khimki, Russia
|
Publication type: Journal Article
Publication date: 2020-12-01
Journal:
Environmental Research
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 8.3
ISSN: 00139351, 10960953
Biochemistry
General Environmental Science
Abstract
Many natural substances exhibit anti-inflammatory activity and considerable potential in prophylaxis and treatment of allergies. Knowing exact molecular targets, which is required for developing these as medicinal products, is often challenging for multicomponent compositions.
In the present study we examined novel polyphenolic substance, a water-soluble fraction of wood lignin (laboratory code BP-Cx-1). In our previous study, a number of polyphenolic components of BP-Cx-1 (flavonoids, sapogenins, phenanthrenes etc.) were identified as the major carriers of biological activity of BP-Cx drug family, and several molecular targets involved in cancer and/or inflammation signaling pathways were proposed based on the results of the in vitro and in silico screening studies.
In the present study, half maximal inhibitory concentration (IC50) of BP-Cx-1 was established with a radioligand method and a range of IC50 values between 22.8 and 40.3 μg/ml were obtained for adenosine receptors A1, A2A and prostaglandin receptors EP2, IP (PGI2). IC50 for serotonin 5-HT1 and for glucocorticoid GR receptors were 3.0 μg/ml and 12.6 μg/ml, respectively, both being within the range of BP-Cx-1 concentrations achievable in in vivo models.
Further, distribution of [3H] labelled BP-Cx-1 in NIH3T3 murine fibroblasts and MCF7/R carcinoma cells was studied with autoradiography. [3H]-BP-Cx-1 (visualized as silver grains produced by tritium beta particles) was mainly localized along the cell membrane, in the perinuclear region and in the nucleus, suggesting ability of BP-Cx-1 to enter cells and bind to membrane or cytosol receptors.
In our experiment, we observed the effect of BP-Cx-1 on maturation of dendritic cells (DCs): downregulation of expression of the lipid-presentation molecule CD1a, co-stimulatory molecules CD80, CD83 and CD 40, decreased production of pro-inflammatory cytokines IL-4 and TNF-α and increased production of anti-inflammatory cytokine IL-10. It is hypothesized that [3H]-BP-Cx-1 detectable in the nucleus is part of the activated GR complex, known to be involved in regulation of transcription of genes responsible for the anti-inflammatory response. Based on IC50, cell distribution data and results of the experiment with DCs it is suggested that the in vivo effects of BP-Cx-1 are mediated via GR and 5-HT1 receptors thus promoting development of tolerogenic effector function in dendritic cells.
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Fedoros E. I. et al. Exploring bioactivity potential of polyphenolic water-soluble lignin derivative. // Environmental Research. 2020. Vol. 191. p. 110049.
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Baldueva I. A., Emelyanova N. V., Danilova A. B., Grozdova I. D., Anisimov V., Bykov V. N., Panchenko A. V., Gubareva E. A., Tyndyk M. L., Semenov A., Ryakhovskiy A. A., Kuznetsova A. I., Nekhaeva T. L., Melik-Nubarov N., Chernysheva M. G., Badun G., Perminova I. V., Fedoros E. I., Pigarev S. E., Perminova I. V., Badun G. A., Chernysheva M. G., Grozdova I. D., Danilova A., Tyndyk M., Gubareva E., Panchenko A., Anisimov V. Exploring bioactivity potential of polyphenolic water-soluble lignin derivative. // Environmental Research. 2020. Vol. 191. p. 110049.
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TY - JOUR
DO - 10.1016/j.envres.2020.110049
UR - https://doi.org/10.1016%2Fj.envres.2020.110049
TI - Exploring bioactivity potential of polyphenolic water-soluble lignin derivative.
T2 - Environmental Research
AU - Fedoros, E I
AU - Baldueva, I A
AU - Perminova, I V
AU - Badun, G.A.
AU - Chernysheva, M G
AU - Melik-Nubarov, N.S.
AU - Nekhaeva, T L
AU - Kuznetsova, A I
AU - Ryakhovskiy, A A
AU - Pigarev, S E
AU - Semenov, A.L.
AU - Tyndyk, M L
AU - Gubareva, E. A.
AU - Panchenko, A. V.
AU - Bykov, V N
AU - Anisimov, V.N.
AU - Grozdova, I D
AU - Danilova, A B
AU - Emelyanova, N V
AU - Perminova, Irina V.
AU - Badun, Gennadii A.
AU - Chernysheva, Maria G
AU - Grozdova, Irina D
AU - Danilova, Anna
AU - Tyndyk, Margarita
AU - Gubareva, Ekaterina
AU - Panchenko, Andrey
AU - Anisimov, V.I.
PY - 2020
DA - 2020/12/01 00:00:00
PB - Elsevier
SP - 110049
VL - 191
SN - 0013-9351
SN - 1096-0953
ER -
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@article{2020_Fedoros,
author = {E I Fedoros and I A Baldueva and I V Perminova and G.A. Badun and M G Chernysheva and N.S. Melik-Nubarov and T L Nekhaeva and A I Kuznetsova and A A Ryakhovskiy and S E Pigarev and A.L. Semenov and M L Tyndyk and E. A. Gubareva and A. V. Panchenko and V N Bykov and V.N. Anisimov and I D Grozdova and A B Danilova and N V Emelyanova and Irina V. Perminova and Gennadii A. Badun and Maria G Chernysheva and Irina D Grozdova and Anna Danilova and Margarita Tyndyk and Ekaterina Gubareva and Andrey Panchenko and V.I. Anisimov},
title = {Exploring bioactivity potential of polyphenolic water-soluble lignin derivative.},
journal = {Environmental Research},
year = {2020},
volume = {191},
publisher = {Elsevier},
month = {dec},
url = {https://doi.org/10.1016%2Fj.envres.2020.110049},
pages = {110049},
doi = {10.1016/j.envres.2020.110049}
}