Abstract
High reactive oxygen species (ROS), Ha-Ras, and active ERK1/2 in fibroblasts play an essential role in the pathogenesis of systemic sclerosis (SSc). The present study was carried out to evaluate the effects of the ethanol extract from fruits of Capparis Spinosa L. (ECS) on oxidative stress and ROS-ERK1/2-Ha-Ras signal loop in SSc dermal fibroblasts in vitro. Cultured dermal fibroblasts from three SSc patients and three normal controls were treated with ECS by different concentration (10, 50, 100 μg/ml). ECS significantly reduced the production of O2 –, H2O2, and ROS in SSc fibroblasts in a dose-dependent manner. ECS effectively minimized the loss of cell viability and apoptosis induced by H2O2 in normal and SSc fibroblasts. Furthermore, the protective effect of ECS on SSc fibroblasts was more significant than on normal ones. ECS decreased the expression of P-ERK1/2 and Ha-Ras in a dose-dependent manner. In conclusion, ECS exhibits a notable activity in protecting against oxidative stress and interrupting of ROS-ERK1/2-Ha-Ras signal loop in SSc, suggesting its potential protective effects against skin sclerosis.
Similar content being viewed by others
Abbreviations
- SSc:
-
Systemic sclerosis
- ECS:
-
The ethanol extract from fruits of Capparis Spinosa L.
- ROS:
-
Reactive oxygen species
- MTT:
-
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
- ERK:
-
Extracellular signal-regulated kinase
- DCFH-DA:
-
Fluorescent probe 2′-7′-Dichlorodihydrofluorescin diacetate
References
Ali-Shtayeh MS, Abu Ghdeib SL (1999) Antifungal activity of plant extracts against dermatophytes. Mycoses 42(11–12):665–672
Andrzej BH (2006) Flavonoid-membrane interactions: possible consequences for biological effects of some polyphenolic compounds. Acta Pharmacol Sin 27(1):27–40
Arora A, Byrem TM, Nair MG, Strasburg GM (2000) Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids. Arch Biochem Biophys 373(1):102–109
Baroni SS, Santillo M, Bevilacqua F, Luchetti M, Spadoni T, Mancini M et al (2006) Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 354(25):2667–2676
Black CM, Stephen C (1993) Systemic sclerosis (scleroderma) and related disorders. In: Maddison PJ, Isenberg DA, Woo P, Glass DN (eds) Oxford textbook of rheumatology. Oxford University, Oxford, pp 771–789
Bonina F, Puglia C, Ventura D, Aquino R, Tortora S, Sacchi A et al (2002) In vitro antioxidant and in vivo photoprotective effects of a lyophilized extract of capparis spinosa L. buds. J Cosmet Sci 53(6):321–335
Calis I, Kuruuzum-Uz A, Ruedi P (1999) 1H-indole-3-acetonitrile glycosides from Capparis spinosa fruits. Phytochemistry 50:1205–1208
Cao YL, Li X, Zheng M (2008) Effect of Capparis spinosa on fibroblast proliferation and type I collagen production in progressive systemic sclerosis. Zhongguo Zhong Yao Za Zhi 33(5):560–563
Chinese Pharmacopoeia Commission (2005) Chinese pharmacopoeia part 1. People’s Health Press, Beijing, p 246
Eddouks M, Lemhadri A, Michel JB (2004) Caraway and caper potential anti-hyperglycaemic plants in diabetic rats. J Ethnopharmacol 94(1):143–148
Eddouks M, Lemhadri A, Michel JB (2005) Hyperlipidemic activity of aqueous extract of Capparis spinosa L. in normal and diabetic rats. J Ethnopharmacol 98(3):345–350
Gadgoli C, Mishra SH (1999) Antihepatotoxic activity of p-methoxy benzoic acid from Capparis spinosa. J Ethnopharmacol 66(2):187–192
Germanò MP, De Pasquale R, D’Angelo V, Catania S, Silvari V, Costa C (2002) Evaluation of extracts and isolated fraction from Capparis Spinosa L. buds as an antioxidant source. J Agric Food Chem 50(5):1168–1171
Jimenez SA, Feldman G, Bashey RI, Bienkowski R, Rosenbloom J (1986) Co-ordinate increase in the expression of type I and type III collagen genes in progressive systemic sclerosis. Biochem J 237:837–843
Kikuchi K, Smith EA, LeRoy EC, Trojanowska M (1992) Direct demonstration of transcriptional activation of collagen gene expression in systemic sclerosis fibroblasts. Biochem Biophys Res Commun 187:45–50
Mossmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63
Orlandini G, Ronda N, Gatti R, Gazzola GC, Borghetti A (1999) Receptor-ligand internalization. Methods Enzymol 307:340–350
Panico AM, Cardile V, Garufi F et al (2005) Protective effect of Capparis spinosa on chondrocytes. Life Sci 77(20):2479–2488
Rodrigo M, Lazaro MJ, Alvarruiz A, Giner V (1992) Composition of capers (Capparis spinosa): influence of cultivar, size and harvest date. J Food Sci 57:1152–1154
Sambo P, Baroni SS, Luchetti M, Paroncini P, Dusi S, Orlandini G et al (2001) Oxidative stress in scleroderma: maintenance of Scleroderma fibroblast phenotype by the constitutive up-regulation of reactive oxygen species generation through the NADPH oxidase complex pathway. Arthritis Rheum 44(11):2653–2664
Sambo P, Jannino L, Candela M, Salvi A, Donini M, Dusi S et al (1999) Monocytes of patients with systemic sclerosis (scleroderma) spontaneously release in vitro increased amounts of superoxide anion. J Invest Dermatol 112:78–84
Sharaf M, El-Ansari MA, Saleh NAM (2000) Quercetin triglycoside from Capparis spinosa. Fitoterapia 71:46–49
Stein CM, Tanner SB, Awad JA, Roberts LJ II, Morrow JD (1996) Evidence of free radical–mediated injury (isoprostane overproduction) in scleroderma. Arthritis Rheum 39:1146–1150
Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic, Therapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590
Svegliati S, Cancello R, Sambo P, Luchetti M, Paroncini P, Orlandini G et al (2005) Platelet-derived growth factor and reactive oxygen species (ROS) regulate Ras protein levels in primary human fibroblasts via ERK1/2. Amplification of ROS and Ras in systemic scleroderma fibroblasts. J Biol Chem 280(43):36474–36482
Trombetta D, Occhiuto F, Perri D, Puglia C, Santagati NA, Pasquale AD et al (2005) Antiallergic and antihistaminic effect of two extracts of Capparis spinosa L. flowering buds. Phytother Res 19(1):29–33
Yamakage A, Kikuchi K, Smith EA, LeRoy EC, Trojanowska M (1992) Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts. J Exp Med 175(5):1227–1234
Valletta EA, Berton G (1987) Desensitization of macrophage oxygen metabolism on immobilized ligands: different effect of immunoglobulin G and complement. J Immunol 138:4366–4373
Acknowledgments
This work was supported by Provincial Natural Science Foundation of Zhejiang Province (Y2080357), and the Science and Technology Foundation of Zhejiang Province Project (2009C33135).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cao, Yl., Li, X. & Zheng, M. Capparis spinosa protects against oxidative stress in systemic sclerosis dermal fibroblasts. Arch Dermatol Res 302, 349–355 (2010). https://doi.org/10.1007/s00403-009-0998-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-009-0998-7