TY  - JOUR
AU  - Čolić, Miodrag
AU  - Bekić, Marina
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Savikin, Katarina
AU  - Miljus, Nataša
AU  - Marković, Milan
AU  - Skrbić, Ranko
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1605
AB  - Pomegranate peel extract (PoPEx) has been shown to have antioxidant and anti-inflammatory properties, but its effect on the adaptive immune system has not been sufficiently investigated. In this study, the treatment of human peripheral blood mononuclear cells (PBMC) with PoPEx (range 6.25-400 mu g/mL) resulted in cytotoxicity at concentrations of 100 mu g/mL and higher, due to the induction of apoptosis and oxidative stress, whereas autophagy was reduced. At non-cytotoxic concentrations, the opposite effect on these processes was observed simultaneously with the inhibition of PHA-induced PBMC proliferation and a significant decrease in the expression of CD4. PoPEx differently modulated the expression of activation markers (CD69, CD25, ICOS) and PD1 (inhibitory marker), depending on the dose and T-cell subsets. PoPEx (starting from 12.5 mu g/mL) suppressed the production of Th1 (IFN-gamma), Th17 (IL-17A, IL-17F, and IL-22), Th9 (IL-9), and proinflammatory cytokines (TNF-alpha and IL-6) in culture supernatants. Lower concentrations upregulated Th2 (IL-5 and IL-13) and Treg (IL-10) responses as well as CD4+CD25hiFoxp3+ cell frequency. Higher concentrations of PoPEx increased the frequency of IL-10- and TGF-beta-producing T-cells (much higher in the CD4+ subset). In conclusion, our study suggested for the first time complex immunoregulatory effects of PoPEx on T cells, which could assist in the suppression of chronic inflammatory and autoimmune diseases.
PB  - MDPI, Basel
T2  - Pharmaceutics
T1  - Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture
IS  - 6
VL  - 14
DO  - 10.3390/pharmaceutics14061140
ER  - 

@article{
author = "Čolić, Miodrag and Bekić, Marina and Tomić, Sergej and Đokić, Jelena and Radojević, Dušan and Savikin, Katarina and Miljus, Nataša and Marković, Milan and Skrbić, Ranko",
year = "2022",
abstract = "Pomegranate peel extract (PoPEx) has been shown to have antioxidant and anti-inflammatory properties, but its effect on the adaptive immune system has not been sufficiently investigated. In this study, the treatment of human peripheral blood mononuclear cells (PBMC) with PoPEx (range 6.25-400 mu g/mL) resulted in cytotoxicity at concentrations of 100 mu g/mL and higher, due to the induction of apoptosis and oxidative stress, whereas autophagy was reduced. At non-cytotoxic concentrations, the opposite effect on these processes was observed simultaneously with the inhibition of PHA-induced PBMC proliferation and a significant decrease in the expression of CD4. PoPEx differently modulated the expression of activation markers (CD69, CD25, ICOS) and PD1 (inhibitory marker), depending on the dose and T-cell subsets. PoPEx (starting from 12.5 mu g/mL) suppressed the production of Th1 (IFN-gamma), Th17 (IL-17A, IL-17F, and IL-22), Th9 (IL-9), and proinflammatory cytokines (TNF-alpha and IL-6) in culture supernatants. Lower concentrations upregulated Th2 (IL-5 and IL-13) and Treg (IL-10) responses as well as CD4+CD25hiFoxp3+ cell frequency. Higher concentrations of PoPEx increased the frequency of IL-10- and TGF-beta-producing T-cells (much higher in the CD4+ subset). In conclusion, our study suggested for the first time complex immunoregulatory effects of PoPEx on T cells, which could assist in the suppression of chronic inflammatory and autoimmune diseases.",
publisher = "MDPI, Basel",
journal = "Pharmaceutics",
title = "Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture",
number = "6",
volume = "14",
doi = "10.3390/pharmaceutics14061140"
}

Čolić, M., Bekić, M., Tomić, S., Đokić, J., Radojević, D., Savikin, K., Miljus, N., Marković, M.,& Skrbić, R.. (2022). Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture. in Pharmaceutics
MDPI, Basel., 14(6).
https://doi.org/10.3390/pharmaceutics14061140

Čolić M, Bekić M, Tomić S, Đokić J, Radojević D, Savikin K, Miljus N, Marković M, Skrbić R. Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture. in Pharmaceutics. 2022;14(6).
doi:10.3390/pharmaceutics14061140 .

Čolić, Miodrag, Bekić, Marina, Tomić, Sergej, Đokić, Jelena, Radojević, Dušan, Savikin, Katarina, Miljus, Nataša, Marković, Milan, Skrbić, Ranko, "Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture" in Pharmaceutics, 14, no. 6 (2022),
https://doi.org/10.3390/pharmaceutics14061140 . .