The stilbenoids, a group of naturally occurring phenolic compounds, are found in a variety of plants, including some berries that are used as food or for medicinal purposes. They are known to be beneficial for human health as anti-inflammatory, chemopreventive, and antioxidative agents. We have investigated a group of 19 stilbenoid substances in vitro using a cellular model of THP-1 macrophage-like cells and pyocyanin-induced oxidative stress to evaluate their antioxidant or pro-oxidant properties. Then we have determined any effects that they might have on the expression of the enzymes catalase, glutathione peroxidase, and heme oxygenase-1, and their effects on the activation of Nrf2. The experimental results showed that these stilbenoids could affect the formation of reactive oxygen species in a cellular model, producing either an antioxidative or pro-oxidative effect, depending on the structure pinostilbene (2) worked as a pro-oxidant and also decreased expression of catalase in the cell culture. Piceatannol (4) had shown reactive oxygen species (ROS) scavenging activity, whereas isorhapontigenin (18) had a mild direct antioxidant effect and activated Nrf2-antioxidant response element (ARE) system and elevated expression of Nrf2 and catalase. Their effects shown on cells in vitro warrant their further study in vivo.

Department of Food Science The Faculty of Agrobiology Food and Natural Resources The Czech University of Life Sciences Prague 16500 Prague Czech Republic

Department of Medicinal Chemistry Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno 61242 Brno Czech Republic

Department of Molecular Biology and Pharmaceutical Biotechnology Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno 61242 Brno Czech Republic

Department of Natural Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno 61242 Brno Czech Republic

Department of Pharmacognosy and Molecular Basis of Phytotherapy Faculty of Pharmacy Medical University of Warsaw 02 097 Warsaw Poland

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Dvorakova M., Landa P. Anti-inflammatory activity of natural stilbenoids: A review. Pharmacol. Res. 2017;124:126–145. doi: 10.1016/j.phrs.2017.08.002. PubMed DOI

Baur J.A., Sinclair D.A. Therapeutic potential of resveratrol: The in vivo evidence. Nat. Rev. Drug Discov. 2006;5:493–506. doi: 10.1038/nrd2060. PubMed DOI

Leláková V., Šmejkal K., Jakubczyk K., Veselý O., Landa P., Václavík J., Bobáľ P., Pížová H., Temml V., Steinacher T., et al. Parallel in vitro and in silico investigations into anti-inflammatory effects of non-prenylated stilbenoids. Food Chem. 2019;285:431–440. doi: 10.1016/j.foodchem.2019.01.128. PubMed DOI

Cottart C.-H., Nivet-Antoine V., Languillier-Morizot C., Beaudeux J.-L. Resveratrol bioavailability and toxicity in humans. Mol. Nutr. Food Res. 2010;54:7–16. doi: 10.1002/mnfr.200900437. PubMed DOI

Hall S., McDermott C., Anoopkumar-Dukie S., McFarland A.J., Forbes A., Perkins A.V., Davey A.K., Chess-Williams R., Kiefel M.J., Arora D., et al. Cellular Effects of Pyocyanin, a Secreted Virulence Factor of Pseudomonas aeruginosa. Toxins. 2016;8:236. doi: 10.3390/toxins8080236. PubMed DOI PMC

D’Andrea G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia. 2015;106:256–271. doi: 10.1016/j.fitote.2015.09.018. PubMed DOI

Granica S., Piwowarski J.P., Randazzo A., Schneider P., Żyżyńska-Granica B., Zidorn C. Novel stilbenoids, including cannabispiradienone glycosides, from Tragopogon tommasinii (Asteraceae, Cichorieae) and their potential anti-inflammatory activity. Phytochemistry. 2015;117:254–266. doi: 10.1016/j.phytochem.2015.06.018. PubMed DOI

Peyrat-Maillard M.N., Cuvelier M.E., Berset C. Antioxidant activity of phenolic compounds in 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidation: Synergistic and antagonistic effects. J. Am. Oil Chem. Soc. 2003;80:1007. doi: 10.1007/s11746-003-0812-z. DOI

Vasantha Rupasinghe H.P., Yasmin A. Inhibition of oxidation of aqueous emulsions of omega-3 fatty acids and fish oil by phloretin and phloridzin. Molecules. 2010;15:251–257. doi: 10.3390/molecules15010251. PubMed DOI PMC

Rastogi R.P., Singh S.P., Häder D.P., Sinha R.P. Detection of reactive oxygen species (ROS) by the oxidant-sensing probe 2′,7′-dichlorodihydrofluorescein diacetate in the cyanobacterium Anabaena variabilis PCC 7937. Biochem. Biophys. Res. Commun. 2010;397:603–607. doi: 10.1016/j.bbrc.2010.06.006. PubMed DOI

Gaschler M.M., Stockwell B.R. Lipid peroxidation in cell death. Biochem. Biophys. Res. Commun. 2017;482:419–425. doi: 10.1016/j.bbrc.2016.10.086. PubMed DOI PMC

Treml J., Šmejkal K. Flavonoids as Potent Scavengers of Hydroxyl Radicals. Comp. Rev. Food Sci. Food Saf. 2016;15:720–738. doi: 10.1111/1541-4337.12204. PubMed DOI

Smoliga J.M., Baur J.A., Hausenblas H.A. Resveratrol and health—A comprehensive review of human clinical trials. Mol. Nutr. Food Res. 2011;55:1129–1141. doi: 10.1002/mnfr.201100143. PubMed DOI

Murias M., Jäger W., Handler N., Erker T., Horvath Z., Szekeres T., Nohl H., Gille L. Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: Structure–activity relationship. Biochem. Pharmacol. 2005;69:903–912. doi: 10.1016/j.bcp.2004.12.001. PubMed DOI

Szekeres T., Saiko P., Fritzer-Szekeres M., Djavan B., Jäger W. Chemopreventive effects of resveratrol and resveratrol derivatives. Ann. N. Y Acad. Sci. 2011;1215:89–95. doi: 10.1111/j.1749-6632.2010.05864.x. PubMed DOI

Kucinska M., Piotrowska H., Luczak M.W., Mikula-Pietrasik J., Ksiazek K., Wozniak M., Wierzchowski M., Dudka J., Jäger W., Murias M. Effects of hydroxylated resveratrol analogs on oxidative stress and cancer cells death in human acute T cell leukemia cell line: Prooxidative potential of hydroxylated resveratrol analogs. Chem.-Biol. Interact. 2014;209:96–110. doi: 10.1016/j.cbi.2013.12.009. PubMed DOI

Jeong S.O., Son Y., Lee J.H., Cheong Y.K., Park S.H., Chung H.T., Pae H.O. Resveratrol analog piceatannol restores the palmitic acid-induced impairment of insulin signaling and production of endothelial nitric oxide via activation of anti-inflammatory and antioxidative heme oxygenase-1 in human endothelial cells. Mol. Med. Rep. 2015;12:937–944. doi: 10.3892/mmr.2015.3553. PubMed DOI PMC

Son Y., Chung H.T., Pae H.O. Differential effects of resveratrol and its natural analogs, piceatannol and 3,5,4′-trans-trimethoxystilbene, on anti-inflammatory hemeoxigenase-1 expression in RAW264.7 macrophages. Biofactors. 2014;40:138–145. doi: 10.1002/biof.1108. PubMed DOI

Saw C.L., Guo Y., Yang A.Y., Paredes-Gonzalez X., Ramirez C., Pung D., Kong A.N. The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: Involvement of the Nrf2-ARE signaling pathway. Food Chem. Toxicol. 2014;72:303–311. doi: 10.1016/j.fct.2014.07.038. PubMed DOI

Pulido R., Bravo L., Saura-Calixto F. Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. J. Agric. Food Chem. 2000;48:3396–3402. doi: 10.1021/jf9913458. PubMed DOI

Halliwell B. Free radicals and antioxidants: Updating a personal view. Nutr. Rev. 2012;70:257–265. doi: 10.1111/j.1753-4887.2012.00476.x. PubMed DOI

Zhou C.X., Kong L.D., Ye W.C., Cheng C.H., Tan R.X. Inhibition of xanthine and monoamine oxidases by stilbenoids from Veratrum taliense. Planta Med. 2001;67:158–161. doi: 10.1055/s-2001-11500. PubMed DOI

Abbas A.M. Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats. J. Physiol. Biochem. 2016;72:469–484. doi: 10.1007/s13105-016-0494-4. PubMed DOI

Wang H., Yang Y.L., Zhang H., Yan H., Wu X.J., Zhang C.Z. Administration of the resveratrol analogues isorhapontigenin and heyneanol-A protects mice hematopoietic cells against irradiation injuries. BioMed Res. Int. 2014;2014 doi: 10.1155/2014/282657. PubMed DOI PMC

Chao J., Li H., Cheng K.W., Yu M.S., Chang R.C., Wang M. Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. J. Nutr. Biochem. 2010;21:482–489. doi: 10.1016/j.jnutbio.2009.02.004. PubMed DOI

Sandoval-Acuna C., Ferreira J., Speisky H. Polyphenols and mitochondria: An update on their increasingly emerging ROS-scavenging independent actions. Arch. Biochem. Biophys. 2014;559:75–90. doi: 10.1016/j.abb.2014.05.017. PubMed DOI

Liu H., Yang J., Huang S., Liu R., He Y., Zheng D., Liu C. Mulberry crude extracts induce Nrf2 activation and expression of detoxifying enzymes in rat liver: Implication for its protection against NP-induced toxic effects. J. Funct. Foods. 2017;32:367–374. doi: 10.1016/j.jff.2017.03.024. DOI

Zhao Y., Song W., Wang Z., Wang Z., Jin X., Xu J., Bai L., Li Y., Cui J., Cai L. Resveratrol attenuates testicular apoptosis in type 1 diabetic mice: Role of Akt-mediated Nrf2 activation and p62-dependent Keap1 degradation. Redox Biol. 2018;14:609–617. doi: 10.1016/j.redox.2017.11.007. PubMed DOI PMC

Esatbeyoglu T., Ewald P., Yasui Y., Yokokawa H., Wagner A.E., Matsugo S., Winterhalter P., Rimbach G. Chemical characterization, free radical scavenging, and cellular antioxidant and anti-inflammatory properties of a stilbenoid-rich root extract of Vitis vinifera. Oxid. Med. Cell. Longev. 2016;2016 doi: 10.1155/2016/8591286. PubMed DOI PMC

Shen Z., Wang Y., Su Z., Kou R., Xie K., Song F. Activation of p62-keap1-Nrf2 antioxidant pathway in the early stage of acetaminophen-induced acute liver injury in mice. Chem. Biol. Interact. 2018;282:22–28. doi: 10.1016/j.cbi.2018.01.008. PubMed DOI

Jia Y.N., Lu H.P., Peng Y.L., Zhang B.S., Gong X.B., Su J., Zhou Y., Pan M.H., Xu L. Oxyresveratrol prevents lipopolysaccharide/d-galactosamine-induced acute liver injury in mice. Int. Immunopharmacol. 2018;56:105–112. doi: 10.1016/j.intimp.2018.01.014. PubMed DOI

Lee H.H., Park S.A., Almazari I., Kim E.H., Na H.K., Surh Y.J. Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling. Arch. Biochem. Biophys. 2010;501:142–150. doi: 10.1016/j.abb.2010.06.011. PubMed DOI

Huang M.-Y., Lin J., Lu K., Xu H.-G., Geng Z.-Z., Sun P.-H., Chen W.-M. Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives. J. Agric. Food Chem. 2016;64:2893–2900. doi: 10.1021/acs.jafc.6b00227. PubMed DOI

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