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.
Banasova M, Sasinkova V, Mendichi R, Perecko T, Valachova K, Juranek I, Soltes L. (2012). Free-radical degradation of high-molar-mass hyaluronan induced by Weissberger’s oxidative system: potential antioxidative effect of bucillamine. Neuro Endocrinol Lett33 Suppl 3: 151–154.
Birdsall T, Kelly G. (1997). Berberine: Therapeutic potential of an alkaloid found in several medicinal plants. vol. Volume 2, p 10: Thorne Research.
Ciz M, Cizova H, Denev P, Kratchanova M, Slavov A, Lojek A. (2010). Different methods for control and comparison of the antioxidant properties of vegetables. Food Control21: 6.
Denev P, Kratchanova M, Ciz M, Lojek A, Vasicek O, Blazheva D, Nedelcheva P, Vojtek L, Hyrsl P. (2014). Antioxidant, antimicrobial and neutrophil-modulating activities of herb extracts. Acta Biochim Pol61: 359–367.
Fontayne A, Dang PM, Gougerot-Pocidalo MA, El-Benna J. (2002). Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect on binding to p22phox and on NADPH oxidase activation. Biochemistry41: 7743–7750.
Georgetti SR, Casagrande R, Di Mambro VM, Azzolini AE, Fonseca MJ. (2003). Evaluation of the antioxidant activity of different flavonoids by the chemiluminescence method. AAPS PharmSci5: E20.
Grael C, Kanashiro A, Kabeya L, Jordão C, Renata R, Gobbo-Neto L, Polizello A, Lucisano-Valim Y, Lopes N, Lopes J. (2010). In vitro study of antioxidant and scavenger properties of phenolic compounds from Lychnophora species. Quim Nova33: 4.
Huang D, Ou B, Prior RL. (2005). The chemistry behind antioxidant capacity assays. J Agric Food Chem53: 1841–1856.
Cheng F, Wang Y, Li J, Su C, Wu F, Xia WH, Yang Z, Yu BB, Qiu YX, Tao J. (2013). Berberine improves endothelial function by reducing endothelial microparticles-mediated oxidative stress in humans. Int J Cardiol167: 936–942.
Jeong HW, Hsu KC, Lee JW, Ham M, Huh JY, Shin HJ, Kim WS, Kim JB. (2009). Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am J Physiol Endocrinol Metab296: E955–964.
Jia L, Liu J, Song Z, Pan X, Chen L, Cui X, Wang M. (2012). Berberine suppresses amyloid-beta-induced inflammatory response in microglia by inhibiting nuclear factor-kappaB and mitogen-activated protein kinase signalling pathways. J Pharm Pharmacol64: 1510–1521.
Ko BS, Choi SB, Park SK, Jang JS, Kim YE, Park S. (2005). Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma. Biol Pharm Bull28: 1431–1437.
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. (2004). Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med10: 1344–1351.
Lee D, Bae J, Kim YK, Gil M, Lee JY, Park CS, Lee KJ. (2013). Inhibitory effects of berberine on lipopolysaccharide-induced inducible nitric oxide synthase and the high-mobility group box 1 release in macrophages. Biochem Biophys Res Commun431: 506–511.
Lee CH, Chen JC, Hsiang CY, Wu SL, Wu HC, Ho TY. (2007). Berberine suppresses inflammatory agents-induced interleukin-1beta and tumor necrosis factor-alpha productions via the inhibition of IkappaB degradation in human lung cells. Pharmacol Res56: 193–201.
Luo A, Fan Y. (2011). Antioxidant activities of berberine hydrochloride. Journal of Medicinal Plants Research5: 6.
Sarna LK, Wu N, Hwang SY, Siow YL, O K. (2010). Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophages. Can J Physiol Pharmacol88: 369–378.
Simoes Pires EN, Frozza RL, Hoppe JB, Menezes Bde M, Salbego CG. (2014). Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved. Brain Res1557: 26–33.
Tan Y, Tang Q, Hu BR, Xiang JZ. (2007). Antioxidant properties of berberine on cultured rabbit corpus cavernosum smooth muscle cells injured by hydrogen peroxide. Acta Pharmacol Sin28: 1914–1918.
Vasicek O, Lojek A, Jancinova V, Nosal R, Ciz M. (2014). Role of histamine receptors in the effects of histamine on the production of reactive oxygen species by whole blood phagocytes. Life Sci100: 67–72.
Yildiz G, Demiryurek AT. (1998). Ferrous iron-induced luminol chemiluminescence: a method for hydroxyl radical study. J Pharmacol Toxicol Methods39: 179–184.
Yokozawa T, Ishida A, Kashiwada Y, Cho EJ, Kim HY, Ikeshiro Y. (2004). Coptidis Rhizoma: protective effects against peroxynitrite-induced oxidative damage and elucidation of its active components. J Pharm Pharmacol56: 547–556.