The health benefits of berberine have been recognized for years. Even so, its effects on human neutrophils, the first line of immune defense, have not been reported. The purpose of this study was to investigate the effects of berberine on the human neutrophil oxidative burst. Reactive oxygen species production was analyzed by luminol-enhanced chemiluminescence. The analysis was performed in spontaneous and stimulated (phorbol myristate acetate (PMA) or opsonized zymosan particles (OZP)) whole blood and isolated neutrophils in the presence or absence of berberine. The effects of berberine on oxidant production in cell-free assays were evaluated using luminescence (H2O2-peroxidase-luminol) and fluorescence (Oxygen Radical Absorbance Capacity - ORAC) techniques. Berberine decreased the production of reactive oxygen species in human whole blood and isolated neutrophils stimulated with either PMA or OZP with a different efficiency (EC50 was 69 μM and 197 μM for PMA and OZP, respectively). The effect was more pronounced in isolated neutrophils. Cell-free assays showed the antioxidant activity of berberine against peroxyl radicals and hydrogen peroxide. Based on our results, we suggest that the effects of berberine on reactive oxygen species production in human neutrophils are due to its antioxidant activity.

Institute of Biophysics Academy of Sciences of the Czech Republic v v i Kralovopolska 135 612 65 Brno Czech Republic

Institute of Experimental Pharmacology and Toxicology Slovak Academy of Sciences Dubravska cesta 9 841 04 Bratislava Slovak Republic

Zoology and Entomology Department Faculty of Science Helwan University Ain Helwan 11795 Cairo Egypt

Zobrazit více v PubMed

Banasova M, Sasinkova V, Mendichi R, Perecko T, Valachova K, Juranek I, Soltes L. Free-radical degradation of high-molar-mass hyaluronan induced by Weissberger’s oxidative system: potential antioxidative effect of bucillamine. Neuro Endocrinol Lett. 2012;33(Suppl 3):151–154. PubMed

Birdsall T, Kelly G. Berberine: Therapeutic potential of an alkaloid found in several medicinal plants. Thorne Research. 1997;2:10.

Ciz M, Cizova H, Denev P, Kratchanova M, Slavov A, Lojek A. Different methods for control and comparison of the antioxidant properties of vegetables. Food Control. 2010;21:6.

Denev P, Kratchanova M, Ciz M, Lojek A, Vasicek O, Blazheva D, Nedelcheva P, Vojtek L, Hyrsl P. Antioxidant, antimicrobial and neutrophil-modulating activities of herb extracts. Acta Biochim Pol. 2014;61:359–367. PubMed

Fontayne A, Dang PM, Gougerot-Pocidalo MA, El-Benna J. Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect on binding to p22phox and on NADPH oxidase activation. Biochemistry. 2002;41:7743–7750. PubMed

Georgetti SR, Casagrande R, Di Mambro VM, Azzolini AE, Fonseca MJ. Evaluation of the antioxidant activity of different flavonoids by the chemiluminescence method. AAPS PharmSci. 2003;5:E20. PubMed PMC

Grael C, Kanashiro A, Kabeya L, Jordão C, Renata R, Gobbo-Neto L, Polizello A, Lucisano-Valim Y, Lopes N, Lopes J. In vitro study of antioxidant and scavenger properties of phenolic compounds from Lychnophora species. Quim Nova. 2010;33:4.

Huang D, Ou B, Prior RL. The chemistry behind antioxidant capacity assays. J Agric Food Chem. 2005;53:1841–1856. PubMed

Cheng F, Wang Y, Li J, Su C, Wu F, Xia WH, Yang Z, Yu BB, Qiu YX, Tao J. Berberine improves endothelial function by reducing endothelial microparticles-mediated oxidative stress in humans. Int J Cardiol. 2013;167:936–942. PubMed

Jeong HW, Hsu KC, Lee JW, Ham M, Huh JY, Shin HJ, Kim WS, Kim JB. Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am J Physiol Endocrinol Metab. 2009;296:E955–964. PubMed

Jia L, Liu J, Song Z, Pan X, Chen L, Cui X, Wang M. Berberine suppresses amyloid-beta-induced inflammatory response in microglia by inhibiting nuclear factor-kappaB and mitogen-activated protein kinase signalling pathways. J Pharm Pharmacol. 2012;64:1510–1521. PubMed

Ko BS, Choi SB, Park SK, Jang JS, Kim YE, Park S. Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma. Biol Pharm Bull. 2005;28:1431–1437. PubMed

Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Li Z, Liu J, Jiang JD. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004;10:1344–1351. PubMed

Lee D, Bae J, Kim YK, Gil M, Lee JY, Park CS, Lee KJ. Inhibitory effects of berberine on lipopolysaccharide-induced inducible nitric oxide synthase and the high-mobility group box 1 release in macrophages. Biochem Biophys Res Commun. 2013;431:506–511. PubMed

Lee CH, Chen JC, Hsiang CY, Wu SL, Wu HC, Ho TY. Berberine suppresses inflammatory agents-induced interleukin-1beta and tumor necrosis factor-alpha productions via the inhibition of IkappaB degradation in human lung cells. Pharmacol Res. 2007;56:193–201. PubMed

Luo A, Fan Y. Antioxidant activities of berberine hydrochloride. Journal of Medicinal Plants Research. 2011;5:6.

Sarna LK, Wu N, Hwang SY, Siow YL, O K. Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophages. Can J Physiol Pharmacol. 2010;88:369–378. PubMed

Simoes Pires EN, Frozza RL, Hoppe JB, Menezes Bde M, Salbego CG. Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved. Brain Res. 2014;1557:26–33. PubMed

Tan Y, Tang Q, Hu BR, Xiang JZ. Antioxidant properties of berberine on cultured rabbit corpus cavernosum smooth muscle cells injured by hydrogen peroxide. Acta Pharmacol Sin. 2007;28:1914–1918. PubMed

Thorpe GH, Kricka LJ. Enhanced chemiluminescent reactions catalyzed by horseradish peroxidase. Methods Enzymol. 1986;133:331–353. PubMed

Vasicek O, Lojek A, Jancinova V, Nosal R, Ciz M. Role of histamine receptors in the effects of histamine on the production of reactive oxygen species by whole blood phagocytes. Life Sci. 2014;100:67–72. PubMed

Yildiz G, Demiryurek AT. Ferrous iron-induced luminol chemiluminescence: a method for hydroxyl radical study. J Pharmacol Toxicol Methods. 1998;39:179–184. PubMed

Yokozawa T, Ishida A, Kashiwada Y, Cho EJ, Kim HY, Ikeshiro Y. Coptidis Rhizoma: protective effects against peroxynitrite-induced oxidative damage and elucidation of its active components. J Pharm Pharmacol. 2004;56:547–556. PubMed