Abstract
Objectives
Studies have documented the anti-inflammatory effects of spices, which may be related to treatment of chronic diseases. The purpose of this study was to evaluate the influence of curcumin and piperine and their association on experimental periodontal repair in rats.
Materials and methods
Periodontitis was induced via the installation of a ligature around the first molar. After 15 days, the ligatures were removed, and the rats were separated into groups (12 animals per group): (i) curcumin, (ii) piperine, (iii) curcumin+piperine, (iv) corn oil vehicle, and (v) control group (animals had ligature-induced periodontitis but were not treated). The compounds were administered daily, for 15 days by oral gavage. Animals were euthanized at 5 and 15 days, and hemimaxillae and gingival tissues were harvested. Bone repair was assessed by μCT (microcomputer tomography). Histological sections were stained with hematoxylin/eosin (H/E) for the assessment of cellular infiltrate or picrosirius red for quantification of collagen content, and subjected to immunohistochemistry for detecting NF-ĸB. Gingival tissues were used to evaluate levels of TGF-β and IL-10 (ELISA).
Results
Curcumin and piperine increased the TGF-β level, significantly improved the collagen repair, and decreased the cellularity and activation of NF-ĸB in the periodontal tissues, but only curcumin caused a significant increase in early bone repair.
Conclusion
Curcumin and piperine promoted a substantive effect on tissue repair; however, there was not synergistic effect of compounds administered in combination.
Clinical relevance
Curcumin and piperine stimulates the tissue repair and may be potential candidates for the treatment of periodontal disease.
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References
Shah A, Amini-Nik S (2017) The role of phytochemicals in the inflammatory phase of wound healing. Int J Mol Sci 18(5):1068.29
Banerjee M, Tripathi LM, Srivastava VM, Puri A, Shukla R (2003) Modulation of inflammatory mediators by ibuprofen and curcumin treatment during chronic inflammation in rat. Immunopharmacol Immunotoxicol 25(2):213–224
Jagetia GC, Aggarwal BB (2007) “Spicing up” of the immune system by curcumin. J Clin Immunol 27(1):19–35
Guimaraes MR, Coimbra LS, de Aquino SG, Spolidorio LC, Kirkwood KL, Rossa C Jr (2011) Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo. J Periodontal Res 46(2):269–279
Guimaraes MR, de Aquino SG, Coimbra LS, Spolidorio LC, Kirkwood KL, Rossa C Jr (2012) Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats. Innate Immun 18(1):155–163
Abdollahi E, Momtazi AA, Johnston TP, Sahebkar A (2018) Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: a nature-made jack-of-all-trades? J Cell Physiol 233(2):830–848
Kant V, Kumar D, Prasad R, Gopal A, Pathak NN, Kumar P, Tandan SK (2017) Combined effect of substance P and curcumin on cutaneous wound healing in diabetic rats. J Surg Res 212:130–145
Kant V, Gopal A, Pathak NN, Kumar P, Tandan SK, Kumar D (2014) Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats. Int Immunopharmacol 20(2):322–330
Kant V, Gopal A, Kumar D, Pathak NN, Ram M, Jangir BL, Tandan SK, Kumar D (2015) Curcumin-induced angiogenesis hastens wound healing in diabetic rats. J Surg Res 193(2):978–988
Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB (2017) Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol 174(11):1325–1348
Shehzad A, Wahid F, Lee YS (2010) Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm (Weinheim) 343(9):489–499
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4(6):807–818
Sehgal A, Kumar M, Jain M, Dhawan DK (2011) Combined effects of curcumin and piperine in ameliorating benzo(a)pyrene induced DNA damage. Food Chem Toxicol 49(11):3002–3006
Elburki MS, Rossa C Jr, Guimaraes-Stabili MR, Lee HM, Curylofo-Zotti FA, Johnson F et al (2017) A chemically modified curcumin (CMC 2.24) inhibits nuclear factor kappaB activation and inflammatory bone loss in murine models of LPS-induced experimental periodontitis and diabetes-associated natural periodontitis. Inflammation 40(4):1436–1449
Zhao S, Ma L, Cao C, Yu Q, Chen L, Liu J (2017) Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy. Int J Nanomedicine 12:2489–2504
Bonferoni MC, Rossi S, Sandri G, Ferrari F (2017) Nanoparticle formulations to enhance tumor targeting of poorly soluble polyphenols with potential anticancer properties. Semin Cancer Biol 46:205–214
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64(4):353–356
Bae GS, Kim MS, Jeong J, Lee HY, Park KC, Koo BS, Kim BJ, Kim TH, Lee SH, Hwang SY, Shin YK, Song HJ, Park SJ (2011) Piperine ameliorates the severity of cerulein-induced acute pancreatitis by inhibiting the activation of mitogen activated protein kinases. Biochem Biophys Res Commun 410(3):382–388
Bhalekar MR, Madgulkar AR, Desale PS, Marium G (2017) Formulation of piperine solid lipid nanoparticles (SLN) for treatment of rheumatoid arthritis. Drug Dev Ind Pharm 43(6):1003–1010
Umar S, Golam Sarwar AH, Umar K, Ahmad N, Sajad M, Ahmad S et al (2013) Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis. Cell Immunol 284(1–2):51–59
Correa MG, Pires PR, Ribeiro FV, Pimentel SZ, Casarin RC, Cirano FR et al (2017) Systemic treatment with resveratrol and/or curcumin reduces the progression of experimental periodontitis in rats. J Periodontal Res 52(2):201–209
Zhou T, Chen D, Li Q, Sun X, Song Y, Wang C (2013) Curcumin inhibits inflammatory response and bone loss during experimental periodontitis in rats. Acta Odontol Scand 71(2):349–356
Steffens JP, Santana LCL, Pitombo JCP, Ribeiro DO, Albaricci MCC, Warnavin S et al (2018) The role of androgens on periodontal repair in female rats. J Periodontol 89(4):486–495
Coimbra LS, Steffens JP, Rossa C Jr, Graves DT, Spolidorio LC (2014) Clopidogrel enhances periodontal repair in rats through decreased inflammation. J Clin Periodontol 41(3):295–302
Coimbra LS, Rossa C Jr, Guimaraes MR, Gerlach RF, Muscara MN, Spolidorio DM et al (2011) Influence of antiplatelet drugs in the pathogenesis of experimental periodontitis and periodontal repair in rats. J Periodontol 82(5):767–777
Hie M, Yamazaki M, Tsukamoto I (2009) Curcumin suppresses increased bone resorption by inhibiting osteoclastogenesis in rats with streptozotocin-induced diabetes. Eur J Pharmacol 621(1–3):1–9
Suresh D, Srinivasan K (2010) Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats. Indian J Med Res 131:682–691
Koshimizu JY, Beltrame FL, de Pizzol JP Jr, Cerri PS, Caneguim BH, Sasso-Cerri E (2013) NF-kB overexpression and decreased immunoexpression of AR in the muscular layer is related to structural damages and apoptosis in cimetidine-treated rat vas deferens. Reprod Biol Endocrinol 11:29
Nguyen DH, Zhou T, Shu J, Mao JH (2013) Quantifying chromogen intensity in immunohistochemistry via reciprocal intensity. Cancer InCytes 2:e. https://doi.org/10.1038/protex.2013.097
Cabrera Ortega AA, Goncalves Vde P, Guimaraes MR, Rossa Junior C, Spolidorio LC (2016) Overexpression of Bcl-2, SOCS 1, 3 and Cdh 1, 2 are associated with the early neoplasic changes in modified 4-nitroquinoline 1-oxide-induced murine oral cancer model. J Oral Pathol Med 45(8):573–580
Mohanty C, Das M, Sahoo SK (2012) Sustained wound healing activity of curcumin loaded oleic acid based polymeric bandage in a rat model. Mol Pharm 9(10):2801–2811
Dinh T, Tecilazich F, Kafanas A, Doupis J, Gnardellis C, Leal E, Tellechea A, Pradhan L, Lyons TE, Giurini JM, Veves A (2012) Mechanisms involved in the development and healing of diabetic foot ulceration. Diabetes 61(11):2937–2947
Kulac M, Aktas C, Tulubas F, Uygur R, Kanter M, Erboga M, Ceber M, Topcu B, Ozen OA (2013) The effects of topical treatment with curcumin on burn wound healing in rats. J Mol Histol 44(1):83–90
Sidhu GS, Singh AK, Thaloor D, Banaudha KK, Patnaik GK, Srimal RC, Maheshwari RK (1998) Enhancement of wound healing by curcumin in animals. Wound Repair Regen 6(2):167–177
Dong Y, Huihui Z, Li C (2015) Piperine inhibit inflammation, alveolar bone loss and collagen fibers breakdown in a rat periodontitis model. J Periodontal Res 50(6):758–765
Marek A, Brodzicki J, Liberek A, Korzon M (2002) TGF-beta (transforming growth factor-beta) in chronic inflammatory conditions—a new diagnostic and prognostic marker? Med Sci Monit 8(7):RA145–RA151
Kuru L, Griffiths GS, Petrie A, Olsen I (2004) Changes in transforming growth factor-beta1 in gingival crevicular fluid following periodontal surgery. J Clin Periodontol 31(7):527–533
Trindade SC, Olczak T, Gomes-Filho IS, Moura-Costa LF, Cerqueira EM, Galdino-Neto M et al (2012) Induction of interleukin (IL)-1beta, IL-10, IL-8 and immunoglobulin G by Porphyromonas gingivalis HmuY in humans. J Periodontal Res 47(1):27–32
Theodoro LH, Ferro-Alves ML, Longo M, Nuernberg MAA, Ferreira RP, Andreati A, Ervolino E, Duque C, Garcia VG (2017) Curcumin photodynamic effect in the treatment of the induced periodontitis in rats. Lasers Med Sci 32(8):1783–1791
Hassumi JS, Mulinari-Santos G, Fabris A, Jacob RGM, Goncalves A, Rossi AC et al (2018) Alveolar bone healing in rats: micro-CT, immunohistochemical and molecular analysis. J Appl Oral Sci 26:e20170326
Vieira AE, Repeke CE, Ferreira Junior Sde B, Colavite PM, Biguetti CC, Oliveira RC et al (2015) Intramembranous bone healing process subsequent to tooth extraction in mice: micro-computed tomography, histomorphometric and molecular characterization. PLoS One 10(5):e0128021
Okamoto T, de Russo MC (1973) Wound healing following tooth extraction. Histochemical study in rats. Rev Fac Odontol Aracatuba 2(2):153–169
Funding
The work was supported by FAPESP (São Paulo Research Foundation) 2010/19660-2 and 2010/20091-2.
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The authors declare that they have no conflict of interest.
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All the experimental protocols were approved by the Ethical Committee for Animal Use (CEUA) of the School of Dentistry at Araraquara – UNESP and performed in accordance with the guidelines from the Brazilian College for Animal Experimentation (COBEA). The reported data conforms to the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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Guimaraes-Stabili, M.R., de Aquino, S.G., de Almeida Curylofo, F. et al. Systemic administration of curcumin or piperine enhances the periodontal repair: a preliminary study in rats. Clin Oral Invest 23, 3297–3306 (2019). https://doi.org/10.1007/s00784-018-2755-9
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DOI: https://doi.org/10.1007/s00784-018-2755-9