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Changes in interleukin 6 and monocyte chemoattractant protein-1 expression levels in 3t3-l1 cells after exposure to agrimonia eupatoria l. extract and subsequent oxidative stimulation with tert-buthyl hydroperoxide reveal possible adaptogenic potential

Yoana Kiselova, Deyana Vankova, Oskan Tasinov, Inna Feklicheva, Irina Potoroko, Diana Ivanova


INTRODUCTION: Synthesis and secretion of many inflammatory factors increase with oxidative stimu- lation and the activity of many transcription factors that regulate synthesis of inflammatory cytokines is in- fluenced by the redox condition in the  cell.

AIM: The aim of the current study was to investigate the effects of aqueous-alcoholic agrimony extract on interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) gene expression levels in cultured preadipocytes under induced oxidative stress  conditions.

MATERIALS AND METHODS: To determine the possible adaptogenic potential of agrimony extract treatment on gene  expression,  preadipocytes were  incubated  in a  medium containing different  amounts  of agrimony extract. Tert-butyl hydroperoxide was used to provoke oxidative response in treated cells. Ex- pression of selected genes was measured using two step quantitative PCR. Results were analyzed using the 2-ΔΔCt   method.

RESULTS: Incubation of preadypocytes with 2.5% agrimony extract resulted in a significant decrease in mRNA levels of MCP-1. Significant increase in IL-6 transcription levels was detected in the cells incubated with 1.25% and 2.5% agrimony extract. Pre-incubation of the cells with agrimony extract prevented subse- quent oxidative induced stimulation of MCP-1 gene expression. Oxidative provocation appeared to decrease the stimulatory activity of agrimony on IL-6 gene  expression.


Agrimonia eupatoria; gene expression; MCP-1; IL-6; 3T3-L1; adaptogenic

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Wang P, Mariman E, Keijer J, Bouwman F, Noben J, Robben J et al. Profiling of the secreted proteins during 3T3-L1 adipocyte differentiation leads to the identification of novel adipokines. Cell Mol Life Sci. 2004;61(18):2405-17.

Bourlier V, Bouloumie A. Role of macrophage tis- sue infiltration in obesity and insulin resistance. Diabetes and Metabolism. 2009;(35):251-60.

Fernández-Sánchez A, Madrigal-Santillán E, Bau- tista M, et al. Inflammation, Oxidative Stress, and Obesity. Int J Mol Sci. 2011;12(5):3117-32.

Bastard JP, Jardel C, Bruckert E, Blondy P, Ca- peau J, Laville M, et al. Elevated levels of interleu- kin 6 are reduced in serum and subcutaneous AT Scripta Scientifica Pharmaceutica, 2017;4(2):7-13 11

Medical University of Varnaof obese women after weight loss. J Clin Endocrinol Metab. 2000;85(9):3338-42.

Dandona P, Al Jada A, Bandyopadhyay A. Inflam- mation: the link between insulin resistance, obesity and diabetes. Trends Immunol.2004;25(1):4-7.

Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Re.2009;29:313-26.

Niu J, Kolattukudy PE. Role of MCP-1 in cardiovas- cular disease: molecular mechanisms and clinical implications. Clin Sci (Lond).2009;117:95-109.

Serrano-Marco L, Chacon MR, Maymo-Masip E, Barroso E, Salvado L, Wabitsch M et al. TNF-al- pha inhibits PPARbeta/delta activity and SIRT1 ex- pression through NF-kappaB in human adipocytes. Biochim Biophys Acta.2012;1821:1177-85.

Zagota I, Dimova E, Debatin KM, Wabitsch M, Ki- etzmann T, Fischer-Posovszky P. Obesity and in-

flammation: reduced cytokine expression due to resveratrol in a human in vitro model of inflamed adipose tissue. Front Pharmacol.2015;6:79.

Correia H, Batista M, Dinis T. The activity of an extract and fraction of Agrimonia eupatoria L. against reactive species. Biofactors.2007;29:91-104.

Kiselova Y, Galunska B, Ivanova D, Yankova T. To- tal antioxidant capacity and polyphenol content correlation in aqueous-alcoholic plant extracts used in phytotherapy. Scr Sci Med.2004;36:11-3.

Saggu S, Kumar R. Possible mechanism of adapto- genic activity of seabuckthorn (Hippophae rham- noides) during exposure to cold, hypoxia and re- straint (C-H-R) stress induced hypothermia and post stress recovery in rats. Food Chem Toxicol. 2007;45(12):2426-33.

Ivanova D, Kiselova-Kaneva Y, Ivanov D. An- tioxidant potential of medicinal herbs from the Northern Black Sea coastal zones. Scr Scir Medr. 2009;41(1):7-10.

Kiselova-Kaneva Y, Tasinov O, Vankova D, Ivanova

D. Ethanol induces IL-6 and TNF-α cytokine and iNOS and COX-2 enzyme gene expression in 3T3- L1 preadipocytes. Scr Sci Med.2012;44(2):31-5.

Livak K, Schmittgen T. Analysis of relative gene ex- pression data using Real-Time quantitative PCR and the 2-ΔΔCt method. Methods.2001;25:402-8.

Allen R, Tresini M. Oxidative stress and gene regulation. Free Radical Biology and Medicine. 2000;28(3):463-99.

Yamamoto Y, Gaynor R. Role of the NF-kB path- way in the pathogenesis of human disease states. Curr Mol Med.2001;1(3):287-96.

Chen B, Wei J, Wang W, Cui G, Zhao Y, Zhu X, et al. Identification of signalling pathways involved in aberrant production of adipokines in adipocytes undergoing oxidative stress. Archives of Medical Research. 2009;40(4):241-8.

Woo H, Kang J, Kawada T, Yoo H, Sung M, Yu

R. Active spice-derived components can in- hibit inflammatory responses of adipose tis- sue in obesity by suppressing inflammatory ac- tions of macrophages and release of monocyte

chemoattractant protein-1 from adipocytes. Life Sci.2007;80(10):926-31.

Norata G, Marchesi P, Passamonti S, Pirillo A, Vio- li F, Catapano A. Anti-inflammatory and anti-ath- erogenic effects of cathechin, caffeic acid and trans- resveratrol in apolipoprotein E deficient mice. Ath- erosclerosis. 2007;191(2):265-71.

Panicker S, Sreenivas P, Babu M, Karunagaran D, Kartha C. Quercetin attenuates Monocyte Che- moattractant Protein-1 gene expression in glucose primed aortic endothelial cells through NF-kappaB and AP-1. Pharmacol Res.2010;62(4):328-36.

Ishikawa Y, Sugiyama H, Stylianou E. Bioflavonoid quercetin inhibits interleukin-1-induced transcrip- tional expression of monocyte chemoattractant protein-1 in glomerular cells via suppression of nu- clear factor-kB. J Am Soc Nephrol.1999;10:2290-6.

Santangelo C, Varà R, Scazzocchio B, Di Benedet- to R, Filesi C, Masella R. Polyphenols, intracellular signalling and inflammation. Annali dell`Istituto Superior de Sanita.2007;43(4):394-405.

Lampronti I, Khan M, Bianchi N, Ather A, Bor- gatti M, Vizziello L, et al. Bangladeshi medicinal plant extracts inhibiting molecular interactions be- tween nuclear factors and target DNA sequences mimicking NF-kappa B binding sites. Medicinal Chemistry.2005;1(4):327-33.

Lampronti I., Khan M., Borgatti M., Bianchi N., Gambari R., 2007. Inhibitory effects of Bangladeshi medicinal plant extracts on interactions between transcription factors and target DNA sequences. Evidence-based Complimentary and Alternative Medicine.2007;5(3):303-12.

Yen G, Chen Y, Chang W, Hsu C. Effects of poly- phenolic compounds on Ñ‚umor necrosis factor-α (TNF-α)-induced changes of adipokines and ox-12 Scripta Scientifica Pharmaceutica, 2017;4(2):7-13

Medical University of Varnaidative stress in 3T3-L1 adipocytes. J Agric Food Chem.2011;59(2):546-51.

Xiao F, Lu F, Xu L. Effect of different parts of Por- tulace oleracea on the levels of TNF-alpha and IL-6 in the supernatant of cultured adipose cell. Zhong- guo Zhong Yao Za Zhi. 2005;30(22):1763-6.

Jaramillo M, Olivier M. Hydrogen peroxide induc- es murine macrophage chemokine gene transcrip- tion via extracellular signal-regulated kinase and cyclic adenosine 5`-monophosphate (cAMP)-de- pendent pathways: involvement of NF-kB, activa- tor protein 1, and cAMP response element binding protein. J Immunol.2002;169:7026-38.



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About The Authors

Yoana Kiselova

Deyana Vankova

Oskan Tasinov

Inna Feklicheva

Irina Potoroko

Diana Ivanova

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