Abstract
To investigate the topical anti-inflammatory activity of the crude extract of Cariniana domestica fruit peels (CdE), its dichloromethane, n-butanol, and ethyl acetate (EtAc) fractions, and steroids (β-sitosterol, lupeol, and stigmasterol) isolated from the EtAc fraction in models of irritant contact dermatitis (ICD) croton oil-induced in mice. We induced skin inflammation by single (acute; 1 mg/ear) and multiple (chronic; 0.4 mg/ear) croton oil application. We topically applied C. domestica (CdE, fractions, and gel formulations) and β-sitosterol, lupeol, and stigmasterol immediately after applying croton oil. HPLC-DAD chromatography of the EtAc fraction and stability of the gel formulations were verified. HPLC-DAD of the EtAc fraction revealed the stigmasterol, lupeol, and β-sitosterol presence. CdE and EtAc fraction gels showed no organoleptic or pH changes at room temperatures. CdE and dichloromethane, n-butanol, and EtAc (1 mg/ear) fractions decreased the acute ear edema with maximum inhibition (Imax) of 97 ± 2, 86 ± 1, 81 ± 4, and 95 ± 2%, respectively. CdE and EtAc fraction gel presented similar effects, with respective Imax of 85 ± 6% (3%;15 mg/ear) and 82 ± 2% (1%;15 mg/ear). β-sitosterol (7.5 μg/ear), lupeol (10 μg/ear), and stigmasterol (5.7 μg/ear) also reduced this parameter by 46 ± 8, 51 ± 7, and 62 ± 7%, respectively. All topical treatments reduced the inflammatory cells’ infiltration in the acute ICD model. CdE reduced the ear edema by 77 ± 4% (1 mg/ear) and the inflammatory cell infiltration in the chronic ICD model. CdE’s anti-inflammatory effect was accompanied by a minimum development of adverse effects. C. domestica demonstrates a promising potential for the development of a topical anti-inflammatory agent.
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Abbreviations
- CdE:
-
Crude extract of C. domestica
- MPO:
-
Myeloperoxidase
- NF-κB:
-
Factor nuclear kappa B
- ICD:
-
Irritant contact dermatitis
- ID50 :
-
Inhibitory dose 50%
- I max :
-
Maximal inhibition
- HTAB:
-
Hexadecyltrimethylammoniumbromide
- TMB:
-
Tetramethylbenzidine
- EDTA:
-
Diaminoethanetetraacetic
- ALT:
-
Alanine aminotransferase
- AST:
-
Aspartate aminotransferase
- s.c.:
-
Subcutaneous
- SEM:
-
Standard error of the mean
- TPA:
-
12-O-Tetradecanoylphorbol-13-acetate
- PKC:
-
Protein kinase C
- PLA2 :
-
Phospholipase A2
- AP-1:
-
Activating protein-1
References
Adami M, Prudente A d S, Mendes DAGB, Horinouchi CD d S, Cabrini DA, Otuki MF (2012) Simvastatin ointment, a new treatment for skin inflammatory conditions. J Dermatol Sci 66:127–135
Akindele AJ, Unachukwu EG, Osiagwu DD (2015) 90 days toxicological assessment of hydroethanolic leaf extract of Ipomoea asarifolia (Desr.) Roem. and Schult. (Convolvulaceae) in rats. J Ethnopharmacol 174:582–594
Bangert C, Brunner PM, Stingl G (2011) Immune functions of the skin. Clin Dermatol 29:360–376
Bellik Y, Boukraâ L, Alzahrani HA, Bakhotmah BA, Abdellah F, Hammoudi SM, Iguer-Ouada M (2012) Molecular mechanism underlying anti-inflammatory and anti-allergic activities of phytochemicals: an update. Molecules 18:322–353
Boligon AA, Piana M, Kubiça TF, Mario DN, Dalmolin TV, Bonez PC, Weiblen R, Lovato L, Alves SH, Campos MMA, Athayde ML (2015) HPLC analysis and antimicrobial, antimycobacterial and antiviral activities of Tabernaemontana catharinensis A. DC. J Appl Biomed 13:7–18
Boller S, Soldi C, Marques MCA, Santos EP, Cabrini DA, Pizzolatti MG, Zampronio AR, Otuki MF (2010) Anti-inflammatory effect of crude extract and isolated compounds from Baccharis illinita DC in acute skin inflammation. J Ethnopharmacol 130:262–266
Brum TF, Camponogara C, da Silva Jesus R, Belke BV, Piana M, Boligon AA, Pires FB, Oliveira SM, da Rosa MB, de Freitas Bauermann L (2016) Ethnopharmacological study and topical anti-inflammatory activity of crude extract from Poikilacanthus glandulosus (Nees) Ariza leaves. J Ethnopharmacol 193:60–67
Cabrini DA, Moresco HH, Imazu P, Pietrovski EF, Gasparin DA, Mendes B, Prudente S, Pizzolatti MG, Brighente MC, Otuki MF (2011) Analysis of the potential topical anti-inflammatory activity of Averrhoa carambola L. in mice. Evid Based Complement Alternat Med 2011:1–7
Cai C, Chen Y, Zhong S, Ji B, Wang J, Bai X, Shi G (2014) Anti-inflammatory activity of N-butanol extract from Ipomoea stolonifera in vivo and in vitro. PLoS One 9:1–9
Chibli LA, Rodrigues KCM, Gasparetto CM, Pinto NCC, Fabri RL, Scio E, Alves MS, Del-Vechio-Vieira G, Sousa OV (2014) Anti-inflammatory effects of Bryophyllum pinnatum (lam.) Oken ethanol extract in acute and chronic cutaneous inflammation. J Ethnopharmacol 154:330–338
Choi J, Kim S (2013) Rutin suppresses atopic dermatitis and allergic contact dermatitis. Exp Biol Med 238:410–417
Cunha LC, Azeredo FS, Mendonça ACV, Vieira MS, Pucci LL, Valadares MC, Freitas HOG, Sena ÂAS, Lino RDS (2009) Avaliação da toxicidade aguda e subaguda, em ratos, do extrato etanólico das folhas e do látex de Synadenium umbellatum Pax. Rev Bras Farmacogn 19:403–411.
Di Meglio P, Perera GK, Nestle FO (2011) The multitasking organ: recent insights into skin immune function. Immunity 35:857–869
Eberting CL (2014) Irritant contact dermatitis: mechanisms to repair. J Clin Exp Dermatol Res 5:4–11
Feingold KR, Schmuth M, Elias PM (2007) The regulation of permeability barrier homeostasis. J Invest Dermatol 127:1574–1576
Fialho MFP, Brusco I, Brum S, Piana M, Boligon AA, Trevisan G, Oliveira SM (2017) Buddleja thyrsoides Lam. crude extract presents antinociceptive effect on an arthritic pain model in mice. 474, 2993–3010
Hernández-Valle E, Herrera-Ruiz M, Salgado GR, Zamilpa A, Ocampo MLA, Aparicio AJ, Tortoriello J, Jiménez-Ferrer E (2014) Anti-inflammatory effect of 3-O-[(6'-O-palmitoyl)-β-D-glucopyranosyl sitosterol] from Agave angustifolia on ear edema in mice. Molecules 19:15624–15637
Horinouchi CDDS, Mendes DAGB, Soley BDS, Pietrovski EF, Facundo VA, Santos ARS, Cabrini DA, Otuki MF (2013) Combretum leprosum Mart. (Combretaceae): potential as an antiproliferative and anti-inflammatory agent. J Ethnopharmacol 145:311–319
Hwang SJ, Kim YW, Park Y, Lee HJ, Kim KW (2014) Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm Res 63:81–90
Ibrahim B, Sowemimo A, Van Rooyen A, Van De Venter M (2012) Antiinflammatory, analgesic and antioxidant activities of Cyathula prostrata (Linn.) Blume (Amaranthaceae). J Ethnopharmacol 141:282–289
Janovik V, Boligon A, Bandeira R, Athayde M (2011) HPLC/DAD analysis, determination of total phenolic and flavonoid contents and antioxidant activity from the leaves of Cariniana domestica (Mart) Miers. Res J Phytochem 5:209–215
Janovik V, Boligon A, Athayde M (2012a) Antioxidant activities and HPLC/DAD analysis of phenolic and carotenoids from the barks of Cariniana domestica (Mart.) Miers. Res J Phytochem 6:105–112
Janovik V, Boligon AA, Frohlich JK, Schwanz TG, Pozzebon TV, Alves SH, Athayde ML (2012b) Isolation and chromatographic analysis of bioactive triterpenoids from the bark extract of Cariniana domestica (Mart) Miers. Nat Prod Res 26:66–71
Khan AQ, Khan R, Qamar W, Lateef A, Ali F, Tahir M, Rehman MU, Sultana S (2012) Caffeic acid attenuates 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced NF-κB and COX-2 expression in mouse skin: abrogation of oxidative stress, inflammatory responses and proinflammatory cytokine production. Food Chem Toxicol 50:175–183
Kumar KG, Dhamotharan R, Kulkarni NM, Mahat MYA, Gunasekaran J, Ashfaque M (2011) Embelin reduces cutaneous TNF-α level and ameliorates skin edema in acute and chronic model of skin inflammation in mice. Eur J Pharmacol 662:63–69
Lee HY, Stieger M, Yawalkar N, Kakeda M (2013) Cytokines and chemokines in irritant contact dermatitis. Mediat Inflamm 2013:1–7
Lee J, Choi YY, Kim MH, Han JM, Lee JE, Kim EH, Hong J, Kim J, Yang WM (2016) Topical application of Angelica sinensis improves pruritus and skin inflammation in mice with atopic dermatitis-like symptoms. J Med Food 19:98–105
Lim KM, Bae SJ, Koo JE, Kim ES, Bae ON, Lee JY (2015) Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester. Arch Dermatol Res 307:219–227
Lisby S, Baadsgaard O (2010) Mechanisms of irritant contact dermatitis, in: Duus, J.J., Frosch, P.J., Leppoittevin, J.P. (Eds.), Contact dermatitis pp. 69–82
Mcgrath JC, Lilley E (2015) Implementing guidelines on reporting research using animals (ARRIVE etc.): new requirements for publication in BJP. Br J Pharmacol 172:3189–3193
Medeiros R, Otuki MF, Avellar MCW, Calixto JB (2007) Mechanisms underlying the inhibitory actions of the pentacyclic triterpene α-amyrin in the mouse skin inflammation induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Eur J Pharmacol 559:227–235
Mendes DAGB, Soley BDS, Prudente ADS, Sponchiado G, Ferreira BGA, dos Santos MC, de Andrade ASM, Amorim CDM, Bresolin TMB, Meyre-Silva C, Zuffellato-Ribas KC, Assreuy J, Otuki MF, Cabrini DDA (2016) Hydroalcoholic extract of Sapium glandulatum (Vell.) Pax displays potent anti-inflammatory activities through a glucocorticoid receptor-dependent pathway. Phytomedicine 23:1610–1620
National Health Surveillance Agency (Anvisa) (2004) Guide of stability to cosmetic products, Brazil
Oliveira SM, Silva CR, Wentz AP, Paim GR, Correa MS, Bonacorso HG, Prudente AS, Otuki MF, Ferreira J (2014) Antinociceptive effect of 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole. A Celecoxib structural analog in models of pathological pain. Pharmacol Biochem Behav 124:396–404
Pandey A, Negi PS (2016) Traditional uses, phytochemistry and pharmacological properties of Neolamarckia cadamba: a review. J Ethnopharmacol 181:118–135
Passos GF, Medeiros R, Marcon R, Nascimento AFZ, Calixto JB, Pianowski LF (2013) The role of PKC/ERK1/2 signaling in the anti-inflammatory effect of tetracyclic triterpene euphol on TPA-induced skin inflammation in mice. Eur J Pharmacol 698:413–420
Phanse MA, Patil MJ, Abbulu K, Chaudhari PD, Patel B (2012) In-vivo and in-vitro screening of medicinal plants for their anti-inflammatory activity: an overview. J Appl Pharm Sci 2:19–33
Piana M, Silva MA, Trevisan G, De Brum TF, Silva CR, Boligon AA, Oliveira SM, Zadra M, Hoffmeister C, Rossato MF, Tonello R, Laporta LV, De Freitas RB, Belke BV, Da Silva Jesus R, Ferreira J, Athayde ML (2013) Antiinflammatory effects of Viola tricolor gel in a model of sunburn in rats and the gel stability study. J Ethnopharmacol 150:458–465
Piana M, Camponogara C, Boligon AA, Machado MM, De Brum TF, Oliveira SM, De Freitas Bauermann L (2016) Topical anti-inflammatory activity of Solanum corymbiflorum leaves. J Ethnopharmacol 179:16–21
Pinto NDCC, Machado DC, Da Silva JM, Conegundes JLM, Gualberto ACM, Gameiro J, Moreira Chedier L, Castañon MCMN, Scio E (2015) Pereskia aculeata miller leaves present in vivo topical anti-inflammatory activity in models of acute and chronic dermatitis. J Ethnopharmacol 173:330–337
Proksch E, Brandner JM, Jensen JM (2008) The skin: an indispensable barrier. Exp Dermatol 17:1063–1072
Santos EN, Lima JC, Noldin VF, Cechinel-Filho V, Rao VS, Lima EF, Schmeda-Hirschmann G, Sousa PT Jr, Martins DT (2011) Anti-inflammatory, antinociceptive and antipyretic effects of methanol extract of Cariniana rubra stem bark in animal models. An Acad Bras Cienc 83:557–566
Saraiva RA, Araruna MKA, Oliveira RC, Menezes KDP, Leite GO, Kerntopf MR, Costa JGM, Rocha JBT, Tomé AR, Campos AR, Menezes IRA (2011) Topical anti-inflammatory effect of Caryocar coriaceum Wittm. (Caryocaraceae) fruit pulp fixed oil on mice ear edema induced by different irritant agents. J Ethnopharmacol 136:504–510
Seyfarth F, Schliemann S, Antonov D, Elsner P (2011) Dry skin, barrier function, and irritant contact dermatitis in the elderly. Clin Dermatol 29:31–36
Shah AS, Alagawadi KR (2011) Anti-inflammatory, analgesic and antipyretic properties of Thespesia populnea Soland ex. Correa seed extracts and its fractions in animal models. J Ethnopharmacol 137:1504–1509
Siddiqui F, Naqvi S, Abidi L, Faizi S, Avesi L (2016) Opuntia dillenii cladode: opuntiol and opuntioside attenuated cytokines and eicosanoids mediated inflammation 182, 221–234
Silva MA, Trevisan G, Klafke JZ, Rossato MF, Walker CIB, Oliveira SM, Silva CR, Boligon AA, Flores FC, Silva CDB, Athayde ML, Ferreira J (2013) Antinociceptive and anti-inflammatory effects of Aloe saponaria haw on thermal injury in rats. J Ethnopharmacol 146:393–401
Simpson BS, Luo X, Costabile M, Caughey GE, Wang J, Claudie DJ, McKinnon RA, Semple SJ (2014) Polyandric acid A, a clerodane diterpenoid from the Australian medicinal plant Dodonaea polyandra, attenuates pro-inflammatory cytokine secretion in vitro and in vivo. J Nat Prod 77:85–91
Slodownik D, Lee A, Nixon R (2008) Irritant contact dermatitis: a review. Australas J Dermatol 49:1–11
Sung YY, Lee AY, Kim HK (2016) Forsythia suspensa fruit extracts and the constituent matairesinol confer anti-allergic effects in an allergic dermatitis mouse model. J Ethnopharmacol 187:49–56
Tian H, Matsuo Y, Fukunaga A, Ono R, Nishigori C, Yodoi J (2013) Thioredoxin ameliorates cutaneous inflammation by regulating the epithelial production and release of pro-inflammatory cytokines. Front Immunol 4:1–12
Trevisan G, Rossato MF, Walker CIB, Oliveira SM, Rosa F, Tonello R, Silva CR, Machado P, Boligon AA, Martins MAP, Zanatta N, Bonacorso HG, Athayde ML, Rubin MA, Calixto JB, Ferreira J (2013) A novel, potent, oral active and safe antinociceptive pyrazole targeting kappa opioid receptors. Neuropharmacology 73:261–273
Trivellatograssi L, Malheiros A, Meyre-Silva C, Da Silva Buss Z, Monguilhott ED, Fröde TS, Da Silva KABS, De Souza MM (2013) From popular use to pharmacological validation: a study of the anti-inflammatory, anti-nociceptive and healing effects of Chenopodium ambrosioides extract. J Ethnopharmacol 145:127–138
Tsang, M.S.M., Jiao, D., Chan, B.C.L., Hon, K.L., Leung, P.C., Lau, C.B.S., Wong, E.C.W., Cheng, L., Chan, C.K.M., Lam, C.W.K., Wong, C.K., 2016. Anti-inflammatory activities of pentaherbs formula, berberine, gallic acid and chlorogenic acid in atopic dermatitis-like skin inflammation. Molecules 21
Vassallo A, De Tommasi N, Merfort I, Sanogo R, Severino L, Pelin M, Della Loggia R, Tubaro A, Sosa S (2013) Steroids with anti-inflammatory activity from Vernonia nigritiana Oliv. & Hiern. Phytochemistry 96:288–298
Xiao X, Xie H, Jian D, Deng Y, Chen X, Li J (2015) Rebounding triad (severe itching, dryness and burning) after facial corticosteroid discontinuation defines a specific class of corticosteroid-dependent dermatitis. J Dermatol 42:697–702
Xu Q, Wang Y, Guo S, Shen Z, Wang Y, Yang L (2014) Anti-inflammatory and analgesic activity of aqueous extract of Flos populi. J Ethnopharmacol 152:540–545
Yeom M, Kim SH, Lee B, Han JJ, Chung GH, Choi HD, Lee H, Hahm DH (2012) Oral administration of glucosylceramide ameliorates inflammatory dry-skin condition in chronic oxazolone- induced irritant contact dermatitis in the mouse ear. J Dermatol Sci 67:101–110
Acknowledgments
We thank Professor Margareth Linde Athayde for donating the extract of C. domestica. We also thank the professor of the Program in Biological Sciences: Toxicological Biochemistry (Federal University of Santa Maria), Vera Morsh, for loaning equipment.
Funding
This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq, Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior - CAPES/PROEX (process no. 23038.005848/2018-31; grant no. 0737/2018) (Brazil), and the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul - FAPERGS and the Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (grant no. 16/2551-0000281-9) and FAPERGS (Grant no. 17/2551-0001082-5). CC is recipient of fellowship from CAPES/PROEX (process no. 88882.182152/2018-01) and SMO is recipient of fellowship from CNPq (Grant no. 307220/2017-6). We also acknowledge fellowships from CNPq and CAPES.
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Participated in research design: G.B.M, C.C., C.R.S., S.M.O.
Conducted experiments: G.B.M, C.C., C.R.S., S.M.O.
Plant material and extractions, gel preparation, accelerated stability study, data analysis, writing, and discussion of these: M.P.
Performed data analysis: C.C., C.R.S., S.M.O.
Wrote or contributed to the writing of the manuscript: G.B.M, C.C., C.R.S., S.M.O.
All the authors reviewed the manuscript.
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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution (approved by Institutional Committee for Animal Care and Use of the Federal University of Santa Maria, number process 9475221015/2015) and guidelines of Brazilian Council of Animal Experimentation—CONCEA—and of U.S. Public Health Service’s Policy on Humane Care and Use of Laboratory Animals—PHS Policy) were also followed.
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Milani, G.B., Camponogara, C., Piana, M. et al. Cariniana domestica fruit peels present topical anti-inflammatory efficacy in a mouse model of skin inflammation. Naunyn-Schmiedeberg's Arch Pharmacol 392, 513–528 (2019). https://doi.org/10.1007/s00210-018-1594-1
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DOI: https://doi.org/10.1007/s00210-018-1594-1