Abstract
Here, we evaluate the anti-inflammatory and wound-healing effects of methanolic crude extract obtained from aerial parts (leaves and branches) of Rubus imperialis Chum. Schl. (Rosaceae) and the pure compound niga-ichigoside F1. Anti-inflammatory activity was determined in vivo and in vitro, and the healing effect was evaluated in surgical lesions in mice skin. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and H2O2-induced oxidative stress were used to determine antioxidant activity. The efferocytosis activity was also determined. The data obtained show that the extract of R. imperialis promote reduction in the inflammatory process induced by lipopolysaccharide (LPS) or carrageenan in the air pouch model; the effects could be reinforced by nitric oxide reduction in LPS-stimulated neutrophils, and an increase in the efferocytosis. The extract showed wound healing property in vitro and in vivo, scavenging activity for DPPH, and cytoprotection in the H2O2-induced oxidative stress in L929 cells. In addition, the compound niga-ichigoside F1 was able to reduce the NO secretion; however, it did not present wound-healing activity in vitro. Together, the data obtained point out the modulatory actions of R. imperialis extract on leukocyte migration to the inflamed tissue, the antioxidant, and the pro-resolutive activity. However, the R. imperialis anti-inflammatory activity may be mediated in parts by niga-ichigoside F1, and on wound healing do not correlated with niga-ichigoside F1.
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Alessandri AL, Sousa LP, Lucas CD, Rossi AG, Pinho V, Teixeira MM (2013) Resolution of inflammation: mechanisms and opportunity for drug development. Pharmacol Ther 139:189–212
Alves AB, dos Santos RS, Calil Sde S, Niero R, Lopes Jda S, Perazzo FF, Rosa PC, Andrade SF, Cechinel-Filho V, Maistro EL (2014) Genotoxic assessment of Rubus imperialis (Rosaceae) extract in vivo and its potential chemoprevention against cyclophosphamide-induced DNA damage. J Ethnopharmacol 153:694–700
Balekar N, Katkam NG, Nakpheng T, Jehtae K, Srichana T (2012) Evaluation of the wound healing potential of Wedelia trilobata leaves. J Ethnopharmacol 141:817–824
Barioni ED, Santin JR, Machado ID, Rodrigues SF, Ferraz-de-Paula V, Wagner TM, Cogliati B, Corrêa Dos Santos M, Machado Mda S, de Andrade SF, Niero R, Farsky SH (2013) Achyrocline satureoides (Lam) D.C. hydroalchoolic extract inhibits neutrophil functions related to innate host defense. Evid Based Complement Alternat Med 2013:787916
Berté PE, da Silva LJ, Comandulli NG, Rangel DW, Monache FD, Filho VC, Niero R, de Andrade SF (2014) Evaluation of the gastroprotective activity of the extracts, fractions, and pure compounds obtained from aerial parts of Rubus imperialis in different experimental models. Naunyn Schmiedebergs Archives of Pharmacology 387:313–319
Bystrom J, Evans I, Newson J, Stables M, Toor I, van Rooijen N, Crawford M, Colville-Nash P, Farrow S, Gilroy DW (2008) Resolution-phase macrophages possess a unique inflammatory phenotype that is controlled by cAMP. Blood Journal 112:4117–4127
Chang HY, Lee HN, Kim W, Surh YJ (2014) Docosahexanenoic acid induces M2 macrophage polarization through peroxisome proliferator-actived receptor y activation. Life Sci 120:39–47
Dalli J (2012) Annexin A1 regulates neutrophil clearance by macrophages in the mouse bone marrow. FASEB J 26:387–396
Degendorfer G (2015) Peroxynitrous acid induces structural and functional modifications to basement membranes and its key component, laminin. Free Radic Biol Med 89:721–733
Erkan N, Ayranci G, Ayranci E (2008) Antioxidant activities of rosemary (Rosmarinus officinalis L.) extract, blackseed (Nigella sativa L.) essential oil, carnosic acid, rosmarinic acid and sesamol. Food Chem 110:76–82
Fadok VA et al. (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-1β, PGE2, and PAF. J Clin Investig 101:890–898
Fröde TS, Souza GE, Calixto JB (2002) The effects of IL-6 and IL-10 and their specific antibodies in the acute inflammatory response induced by carrageenan in the mouse model of pleurisy. Cytokine 17:149–156
Gilroy D, Maeyer DR (2015) New insights into the resolution of inflammation. Semin Immunol 27:161–168
Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551
Gregory CD, Pound JD (2010) Microenvironmental influences of apoptosis in vivo and in vitro. Apoptosis 15:1029–1049
He W, Qu T, Yu Q, Wang Z, Lv H, Zhang J, Zhao X, Wang P (2013) LPS induces IL-8 expresssion through TLR4, MyD88, NF-κB and MAPK pathways in human dental pulp stem cells. Int Endod J 46:128–136
Headland SE, Norling LV (2015) The resolution of inflammation: principles and challenges. Semin Immunol 27:149–160
Jitsanong T (2011) Diarylheptanoid 7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene from Curcuma Comosa Roxb. Protects retinal pigment epithelial cells against oxidative stress-induced cell death. Toxicol in Vitro 25:167–176
Kruger P, Saffarzadeh M, Weber AN, Rieber N, Radsak M, von Bernuth H, BenarafaC RD, Skokowa J, Hartl D (2015) Neutrophils: between host defence, immune modulation, and tissue injury. PLoS Pathog 11:e1004651
Laskin DL, Sunil VR, Gardner CR, Laskin JD (2011) Macrophages and tissue injury: agents of defense or destruction? Annu Rev Pharmacol Toxicol 51:267–288
Li J, Du LF, He Y, Yang L, Li YY, Wang YF, Chai X, Zhu Y, Gao XM (2015) Chemical constituents and biological activities of plants from the genus Rubus. Chem Biodivers 12:1809–1847
Machado ID, Santin JR, Drewes CC, Gil CD, Oliani SM, Perretti M, Farsky SH (2014) Alterations in the profile of blood neutrophil membrane receptors caused by in vivo adrenocorticotrophic hormone actions. Am J Physiol Endocrinol Metab 307:E754–E763
Mahato SB, Kundu AP (1994) 13C-NMR spectra of pentacyclic triterpenoids—a compilation and some salient features. Phytochemistry 37:1517–1575
Mantovani A, Cassatella MA, Costantini C, Jaillon S (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519–531
Marlow GJ, van Gent D, Ferguson LR (2013) Why interleukin-10 supplementation does not work in Crohn's disease patients. World Journal Gastroenterology 19:3931–3941
Mcneill E, Channon KM (2012) The role of tetrahydrobiopterin (BH4) in inflammation and cardiovascular disease. J Thromb Haemost 108:832–839
Murad S (2014) Toll-like receptor 4 in inflammation and angiogenesis: a double-edged sword. Front Immunol 7:313
Niero R, Cechinel-Filho V (2008) Therapeutic potential and chemical composition of plants from the genus Rubus: a mini review of the last 10 Years. Natural Products Communications 3:437–444
Niero R, Cechinel Filho V, Souza MM, Montanari JL, Yunes RA, Delle Monache F (1999) Antinociceptive activity of niga-ichigoside F1 from Rubus imperialis. J Nat Prod 62:1145–1146
Niero R, Kanegusuku M, Souza MM, Yunes RA, Cechinel-Filho V (2002). Antinociceptive action of extracts and fractions from Rubus imperialis (Rosaceae). Therapie 57:242-245
Ortega-Gómez A, Perretti M, Soehnlein O (2013) Resolution of inflammation: an integrated view. EMBO Molecular Medicine 5:661–674
Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 97:55–74
Saleh TS, Calixto JB, Medeiros YS (1999) Effects of anti-inflammatory drugs upon nitrate and myeloperoxidase levels in the mouse pleurisy induced by carrageenan. Peptides 20:949–956
Silva AM, Machado ID, Santin JR, de Melo IL, Pedrosa GV, Genovese MI, Farsky SH, Mancini-Filho J (2015) Aqueous extract of Rosmarinus officinalis L. Inhibits neutrophil influx and cytokine secretion. Phytother Res 29:125–133
Soehnlein O, Lindbom L (2010) Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol 10:427–439
Sudsai T, Wattanapiromsakul C, Nakpheng T (2013) Tewtrakul S (2013). Evaluation of the wound healing property of Boesenbergia Longiflora rhizomes. J Ethnopharmacol 150:223–231
Süntar I (2011) Wound healing activity of Rubus sanctus Schreber (Rosaceae): preclinical study in animal models. Evid Based Complement Alternat Med 2011:816156
Tewtrakul S, Tungcharoen P, Sudsai T, Karalai C, Ponglimanont C, Yodsaoue O (2015) Antiinflammatory and wound healing effects of Caesalpinia sappan. Phytother Res 29:850–856
Um BH, Pouplin T, Lobstein A, Weniger B, Litaudon M, Anton R (2001) Phytochemical communication Saponins from Strasburgeria robusta. Fitoterapia 72:591–593
Vedula SR, Ravasio A, Lim CT, Ladoux B (2013) Collective cell migration: a mechanistic perspective. Physiology (Bethesda) 28:370–379
Vestweber D (2015a) How leukocytes cross the vascular endothelium. Nat Rev Immunol 15:692–704
Vestweber D (2015b) How leukocytes cross the vascular endothelium. Nat Rev Immunol 15:692–704
Acknowledgments
The authors are grateful to the Conselho Nacional de Pesquisa e Tecnologia (CNPq, process n. 444682/2014-7), UNIVALI, and FAPESC for their financial support.
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Tonin, T.D., Thiesen, L.C., de Oliveira Nunes, M.L. et al. Rubus imperialis (Rosaceae) extract and pure compound niga-ichigoside F1: wound healing and anti-inflammatory effects. Naunyn-Schmiedeberg's Arch Pharmacol 389, 1235–1244 (2016). https://doi.org/10.1007/s00210-016-1285-8
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DOI: https://doi.org/10.1007/s00210-016-1285-8