Abstract
Pods of Caesalpinia ferrea, popularly used to treat inflammatory processes, were collected to obtain the polysaccharide-rich extract, presenting anti-inflammatory and antinociceptive effects in acute inflammation models. This study aimed to evaluate the anti-inflammatory, antinociceptive and healing activities of the polysaccharide-rich extract from Caesalpinia ferrea pods (PEp-Cf) in the rat model of cutaneous excisional wound. PEp-Cf (0.025–0.1%) or 0.9% NaCl was topically applied in the wounds at dorsal thoracic region (2×/day) during 21 days for measurement of clinical signs (hyperemia, inflammatory exudate, edema, nociception), wound size, histopathological/histomorphometric, oxidative/inflammatory markers and systemic toxicity. PEp-Cf at 0.1% reduced wound area and increased ulcer contraction [days 2 and 10 (21–78%)]. PEp-Cf reduced clinical signs [days 2 and 5 (2.2–2.8×)] and modulated the healing inflammatory phase via stimulation of epithelialization (days 10 and 14), and inhibition of polymorphonuclears [days 2 and 5 (71–74%)], protein leakage [days 2 and 5 (28–41%)], nitrate [days 2 and 5 (2.2–6×)] and malondialdehyde [days 2 and 5 (46–49%)]. PEp-Cf increased the number of blood vessels [days 5 and 7 (3.1–9.6×)], fibroblasts [days 5 and 7 (2.1–6.4×)] and collagen [days 5 to 14 (1.5–1.8×)]. In conclusion, the topical application of PEp-Cf at 0.1% accelerates the healing process of rat cutaneous wounds via modulation of the inflammatory and proliferative phases, being devoid of systemic alterations.
Similar content being viewed by others
Data availability
Enquiries about data availability should be directed to the authors.
References
Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8:464–478
Araujo DF, Madeira JC, Cunha AP, Ricardo NMPS, Bezerra FF, Mourão PAS, Assreuy MAS, Pereira MG et al (2021) Structural characterization of anticoagulant and antithrombotic polysaccharides isolated from Caesalpiniaferrea stem barks. Int J Biol Macromol 21:141–8130
Ayman A, Hiroshi U, Yuji U (2011) The effect of aloe vera oral administration on cutaneous wound healing in type 2 diabetic rats. J Vet Med Sci 73:583–589
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Bradley PP, Priebat DA, Christensen RD, Rothstei G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Investig Dermatol 78:206–209
Braga R (1976) Plantas do Nordeste, especialmente do Ceará. Fortaleza: Departamento Nacional de Obras Contra as Secas540
Brizeno ALS et al (2016) Delayed healing of oral mucosa in a diabetic rat model: implication of TNF-α, IL-1β and FGF-2. Life Sci 155:36–47
Carvalho JCT, Teixeira JRM, Souza PJC, Bastos JK, Santos-Filho D, Sarti SJ (1996) Preliminary studies of analgesic and anti-inflammatory properties of Caesalpiniaferrea crude extract. J Ethnopharmacol 53:175–178
Cighetti G, Debiasi S, Paroni R, Allevi P (1999) Free and total malondialdehyde assessment in biological matrices by gas chromatography-mass spectrometry: what is needed for an accurate detection. Anal Biochem 266:222–229
Da Silva PP et al (2018) The polysaccharide-rich tea of Ximeniaamericana barks prevents indomethacin-induced gastrointestinal damage via neutrophil inhibition. J Ethnopharmacol 224:195–201
Dubois M, Gilles KA, Hamilton JK, Rebers PA, Smith F (1956) Colorimetric method for determination of sugars and related substances. Anal Chem 28:350–356
Er TK, Tsai SM, Wu SH, Chiang W, Lin HC, Lin SF, Wu SH, Tsai LY, Liu TZ (2009) Antioxidant status and superoxide anion radical generation in acute myeloid leukemia. Clin Biochem 40:1015–1019
Farris AB, Catherine DA, Nicole B, Patricia ADP, Collins AB, Ellie M, Neal S, Paul CG, Robert BC (2011) Morphometric and Visual Evaluation of Fibrosis in Renal Biopsies. J Am Soc Nephrol 22:176–186
Ferreira MRA, Soares LAL (2015) Libidibiaferrea (Mart. exTul.) a review of the biological activities and phytochemical composition 9:140–150
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138
Grosu I, Kock M (2011) New concepts in acute pain management: strategies to prevent chronic postsurgical pain, opioid-induced hyperalgesia, and outcome measures. Anesthesiol Clin 29:311–327
Heng MCY (2011) Wound healing in adult skin: aiming for perfect regeneration. Int J Dermatol 50:1058–1066
Holanda BF, Freitas de Araujo D, da Silva JNR, Pereira MG, de Freitas PA, Assreuy AM (2021) Polysaccaride-rich extract of Caesalpinaferrea stem barks attenuates mice acute inflammation induced by zymosan: oxidative stress modulation. J Ethnopharmacol 267:113501
Jettanacheawchankit S, Sasithanasate S, Sangvanich P, Banlunara W, Thunyakitpisal P (2009) Acemannan stimulates gingival fibroblast proliferation; expressions of keratinocyte growth factor-1, vascular endothelial growth factor, and type I collagen and wound healing. J Pharmacol Sci 109:525–531
Katz LB, Theobald HM, Bookstaff RC, Peterson RE (1984) Characterization of the enhanced paw edema response to carrageen and dextran in 2,3,7,9-tetrachlorodibenzo-p-dioxin-treated rats. J Pharmacol Exp Ther 230:670–677
Klaumann PR, Wouk AFPF, Sillas T (2008) Pathophysiology of pain. Arch Vet Sci 13:1–12
Kobayashi YTS, Almeida VT, Bandeira T, Alcántara BN, Silva ASB, Barbosa WLR, Silva PB, Monteiro MVB, Almeida MB (2015) Avaliação fotoquímica e potencial cicatrizante do extrato etanólico dos frutos de Jucá (Libidibiaferrea) em ratos Wistar. Braz J Vet Res Anim Sci 52:34–40
Lima MFF, Araujo Silva JWS, Silva JK, Moura AHN, Lopes RLF, Cordeiro BA, Cordeiro RP, Melo AFM (2019) Avaliação toxicológica através do bioensaio com Artemia salina Leach de espécimes vegetais pertencentes à caatinga. Brazilian Journal of Health Research 2:5950–5963
Liu J, Willfo S, Xu C (2015) A review of bioactive plant polysaccharides: biological activities, functionalization and biomedical applications. Bioact Carbohydr Diet Fibre 5:31–61
Luo Y, Diao H, Xia S, Dong L, Chen J, Zhang J (2010) A physiologically active polysaccharide hydrogel promotes wound healing. J Biomed Mater Res 94:193–204
Madeira JC, da Silva GVL, Batista JJ, Saraiva GD, Santos GRC, Assreuy AMS, Mourão PAS, Pereira MG (2018) An arabinogalactan-glycoconjugate from Genipaamericana leaves present anticoagulant, antiplatelet and antithrombotic effects. Carbohyd Polym 202:554–562
Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142
Mukinda JT, Syce JA (2007) Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents. J Ethnopharmacol 112:138–144
Nakamura ES, Kurosaki F, Arisawa M, Mukainaka T, Takayasu J, Okuda M, Tokuda H, Nishino H, Pastore F (2002) Cancer chemopreventive effects of a Brazilian folk medicine, Jucá, on in vivo two stage skin carcinogenesis. J Ethnopharmacol 81:135–137
Nonato DTT, Vasconcelos SMM, Mota MRL, de Barros Silva PG, Cunha AP, Ricardo NMPS, Pereira MG, Assreuy AMS, Chaves EMC (2018) The anticonvulsant effect of a polysaccharide-rich extract from Genipaamericana leaves is mediated by GABA receptor. Biomed Pharmacother 101:181–187
Okonkwo UA, Dipietro LA (2017) Diabetes and wound angiogenesis. Int J Mol Sci 18:1419–1434
Oliveira AF, Batista JS, Paiva ES, Silva AE, Farias YJMD, Damasceno CAR, Brito PD, Queiroz SAC, Rodrigues CMF, Freitas CIA (2010) Avaliação da atividade cicatrizante do jucá (Caesalpiniaferrea Mart. exTul. var. ferrea) em lesões cutâneas de caprinos. Revista Brasileira De Plantas Medicinais 12:302–310
Pedrosa TN, Barros AO, Nogueira JR, Fruet AC, Rodrigues IC, Calcagno DQ, Smith MAC, Souza TP, Barros SBM, Vasconcellos MC (2016) Anti-wrinkle and anti-whitening effects of jucá (Libidibiaferrea Mart.) extracts. Arch Dermatol Res 308:643–654
Pereira LP, Mota MRL, Brizeno LA, Nogueira FC, Pereira MG, Assreuy AM (2016) Modulator effect of a polysaccharide-rich extract from Caesalpiniaferrea stem barks in rat cutaneous wound healing: role of TNF-α, IL-1β, NO, TGF-β. J Ethnopharmacol 187:213–223
Pereira RF, Bartolo PJ (2016) Traditional therapies for skin wound healing. Adv Wound Care 5:208–229
Pereira LP, Silva RO, Bringel PH, Silva KE, Assreuy AM, Pereira MG (2012) Polysaccharide fractions of Caesalpiniaferrea pods: potential anti-inflammatory usage. J Ethnopharmacol 139:642–648
Pickler TB, Lopes KP, Magalhães SA, Krueger CMA, Martins MM, Filho VC, Jozala AF, Grotto D, Gerenutti M (2019) Effect of Libidibiaferrea bark and seed in maternal reproductive and biochemical outcomes and fetal anomaly in rats. Birth Defects Research 111:863–871
Portou MJ, Bakera D, Abraham D, Tsui J (2015) The innate immune system, toll-like receptors and dermal wound healing: a review. Vascul Pharmacol 71:31–36
Prazeres LDKT, Aragão TP, Brito SA, Almeida CLF, Silva AD, Paula MMF, Farias JS, Vieira LD, Damasceno BPGL, Rolim LA (2019) Antioxidant and antiulcerogenic activity of the dry extract of pods of Libidibiaferrea Mart. exTul. (Fabaceae). Oxid Med Cell Longev 2019:1–23
Queiroz MLS, Justo GZ, Valadares MC, Silva FRP (2001) Evaluation of Caesalpiniaferrea extract on bone marrow hematopoiesis in the murine models of listeriosis and Ehrlich ascites tumor. Immunopharmacol Immunotoxicol 23:367–382
Ramsey DT, Pope ER, Wagner C, Berg JN, Swaim SF (1995) Effects of three occlusive dressing materials on healing of full-thickness skin wounds in dogs. Am J Vet Res 56:941–949
Romana-Souza B, Porto LC, Costa AMA (2010) Cutaneous wound healing of chronically stressed mice is improved catecholamines blockade. Exp Dermatol 19:821–829
Schirato GV, Monteiro FMFS, Carneiro AMA (2006) The polysaccharide from Anacardiumoccidentale L. in the inflammatory phase of the cutaneous wound healing. Ciência Rural 36:149–154
Shahbuddin M, Shahbuddin D, Bullock AJ, Ibrahim H, Rimmer S, Macneil S (2013) High molecular weight plant heteropolysaccharides stimulate fibroblasts but inhibit keratinocytes. Carbohyd Res 13:90–99
Shetty S, Udupa S, Udupa L, Somayaji N (2006) Wound healing activity of Ocimum sanctum Linn with supportive role of antioxidant enzymes. Indian J Physiol Pharmacol 50:163–168
Siddiqui N, Rauf A, Latif A, Mahmood Z (2017) Spectrophotometric determination of the total phenoliccontent, spectral and fluorescence study of the herbal Unanidrug Gul-eZoofa. Journal of Taibah University of Science 12:360–363
Silva F, Sales M, Sá O, Santana G, Deus M, Sousa J, Ferreira P, Peron A (2015) Potencial citotóxico, genotóxico e citoprotetor de extratos aquosos de Caesalpiniapyramidalis Tul., Caesalpiniaferrea Mart. e Caesalpiniapulcherrima Sw. Revista Brasileira Biociências 2015:101–109
Singer AJ, Cark RA (1999) Mechanism of disease: cutaneous wound healing. N Engl J Med 341:738–746
Sivamani RK, Ma BR, Wehrli LN, Maverakis E (2012) Phytochemicals and naturally derived substances for wound healing. Adv Wound Care 1:213–217
Stephen YG, Emelia K, Francis A, Kofi A, Eric W (2010) Wound healing properties and kill kinetics of Clerodendronsplendens G. Don, a Ghanaian wound healing plant. Pharmacognosy Research 2:63–68
Teo S, Stirling D, Thomas S, Hoberman A, Kiorpes A, Khetani V (2002) A 90-day oral gavage toxicity study of p-methylphenidate and d, l-methylphenidate in Sprague-Dawley rats. Toxicology 179:183–196
Wang PH et al (2018) Wound healing. J Chin Med Assoc 81:94–101
Wlascheck M, Scharffetter-Kochanek K (2005) Oxidative stress in chronic venous leg ulcers. Wound Repair Regeneration 13:452–461
Zippel J, Deters A, Hensel A (2009) Arabinogalactans from Mimosa tenuiflora (Willd.) Poiret bark as active principles for wound-healing properties: specific enhancement of dermal fibroblast activity and minor influence on HaCaT keratinocytes. J Ethnopharmacol 30:391–396
Acknowledgements
This work was supported by the Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES, finance code 001). The authors thank Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq, Fundação Cearense de Amparo a Pesquisa-FUNCAP. Assreuy AM are senior investigators of CNPq—(Process No. 308433/2017-3). Statistical review: Paulo Goberlânio de Barros Silva.
Author information
Authors and Affiliations
Contributions
Project supervision: MRLM, AMSA. Polysaccharid extraction: MGP. Execution of methodology: TVM, LPP, DQS. Review and writing: JRLCF, MRLM, AMSA, MGP, APNNA.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Mota, M.R.L., do Carmo Filho, J.R.L., Martins, T.V. et al. Polysaccharide extract of Caesalpinia ferrea (Mart) pods attenuates inflammation and enhances the proliferative phase of rat cutaneous wounds. Inflammopharmacol 30, 1799–1810 (2022). https://doi.org/10.1007/s10787-022-01024-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-022-01024-9