Clinical Oral Investigations

, Volume 22, Issue 3, pp 1449–1461 | Cite as

Mate tea (Ilex paraguariensis) improves bone formation in the alveolar socket healing after tooth extraction in rats

  • Matheus da Silva Brasilino
  • Camila Tami Stringhetta-Garcia
  • Camila Scacco Pereira
  • Ariana Aparecida Ferreira Pereira
  • Karina Stringhetta
  • Andréia Machado Leopoldino
  • Marcelo Macedo Crivelini
  • Edilson Ervolino
  • Rita Cássia Menegati Dornelles
  • Ana Cláudia de Melo Stevanato Nakamune
  • Antonio Hernandes Chaves-Neto
Original Article



The objective of this study was to investigate the effects of mate tea (MT) [Ilex paraguariensis] on alveolar socket healing after tooth extraction.

Materials and methods

Sixteen male rats were divided into MT and control groups. MT was administered by intragastric gavage at a dose of 20 mg/kg/day for 28 days before and 28 days after right maxillary incisor extraction. The control group received an equal volume of water. Histopathological and histometric analysis of the neoformed bone area and osteocyte density were performed, as well as immunohistochemical analysis of osteocalcin (OCN), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and manganese superoxide dismutase (MnSOD) in the alveolar socket. Calcium, phosphorus, alkaline phosphatase (ALP) activity, total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in plasma, whereas TRAP activity was determined in serum.


Histometry evidenced an increase in bone area (P < 0.0001) and osteocyte density (P < 0.0001). MT increased immunolabeling of MnSOD (P < 0.001), OCN (P < 0.0001), RANKL (P < 0.001), OPG (P < 0.0001), and TRAP (P < 0.001). Calcium and phosphorus concentrations did not differ between the groups. In addition, MT enhanced ALP (P < 0.05) and TRAP (P < 0.0001) activities. MT increased the TAC (P < 0.001), whereas it reduced MDA concentrations (P < 0.0001).


MT increases bone area and osteocyte density in the alveolar socket healing on day 28 after tooth extraction.

Clinical relevance

Regular MT ingestion improves the antioxidant defenses and bone formation, which is beneficial for alveolar socket bone healing after tooth extraction.


Ilex paraguariensis Tooth extraction Wound healing Antioxidant 



The authors would like to thank José Marcelo Tramarin, Araçatuba School of Dentistry, UNESP - Univ Estadual Paulista, Department of Pathology and Clinical Propaedeutic, Brazil, for technical assistance.


For this study, no funding was obtained.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The study was conducted according to the national (CONCEA—National Association for Animals Experiments Control: and institutional laws and it was approved by the Ethics Committee on Animal Use (CEUA), of the São Paulo State University (Unesp), School of Dentistry, Araçatuba, São Paulo, Brazil (Authorization Protocol 2013-01572). All surgery was performed under ketamine anesthesia, and all efforts were made to minimize suffering.

Informed consent

For this type of study, formal consent is not required.


  1. 1.
    Lalani Z, Wong M, Brey EM, Mikos AG, Duke PJ (2003) Spatial and temporal localization of transforming growth factor-beta1, bone morphogenetic protein-2, and platelet-derived growth factor-a in healing tooth extraction sockets in a rabbit model. J Oral Maxillofac Surg 61:1061–1072CrossRefPubMedGoogle Scholar
  2. 2.
    Pinho MN, Roriz VL, Novaes AB, Taba M, Grisi MF, de Souza SL, Palioto DB (2006) Titanium membranes in prevention of alveolar collapse after tooth extraction. Implant Dent 15:53–61. CrossRefPubMedGoogle Scholar
  3. 3.
    Chen LL, Tang Q, Yan J (2004) Therapeutic effect of aqueous-extract from a traditional Chinese medical herb Drynaria fortunei on rat experimental model of alveolar bone resorption. Zhongguo Zhong Yao Za Zhi 29:549–553PubMedGoogle Scholar
  4. 4.
    Shen CL, Yeh JK, Cao JJ, Tatum OL, Dagda RY, Wang JS (2010) Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats. Osteoporos Int 21:1841–1852. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rodan GA, Martin TJ (2000) Therapeutic approaches to bone diseases. Science 289:1508–1514CrossRefPubMedGoogle Scholar
  6. 6.
    Colli VC, Okamoto R, Spritzer PM, Dornelles RC (2012) Oxytocin promotes bone formation during the alveolar healing process in old acyclic female rats. Arch Oral Biol 57:1290–1297. CrossRefPubMedGoogle Scholar
  7. 7.
    Raymond MH, Schutte BC, Torner JC, Burns TL, Willing MC (1999) Osteocalcin: genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis. Genomics 60:210–217. CrossRefPubMedGoogle Scholar
  8. 8.
    Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536. CrossRefPubMedGoogle Scholar
  9. 9.
    Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473:139–146. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kearns AE, Khosla S, Kostenuik PJ (2008) Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 29:155–192. CrossRefPubMedGoogle Scholar
  11. 11.
    Sarsour EH, Kumar MG, Chaudhuri L, Kalen AL, Goswami PC (2009) Redox control of the cell cycle in health and disease. Antioxid Redox Signal 11:2985–3011. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sen CK, Roy S (2008) Redox signals in wound healing. Biochim Biophys Acta 1780:1348–1361. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Guo S, Dipietro LA (2010) Factors affecting wound healing. J Dent Res 89:219–229. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Yeler H, Tahtabas F, Candan F (2005) Investigation of oxidative stress during fracture healing in the rats. Cell Biochem Funct 23:137–139. CrossRefPubMedGoogle Scholar
  15. 15.
    Cutando A, Arana C, Gómez-Moreno G, Escames G, López A, Ferrera MJ, Reiter RJ, Acuña-Castroviejo D (2007) Local application of melatonin into alveolar sockets of beagle dogs reduces tooth removal-induced oxidative stress. J Periodontol 78:576–583. CrossRefPubMedGoogle Scholar
  16. 16.
    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 20:322–330. CrossRefPubMedGoogle Scholar
  17. 17.
    Battino M, Bullon P, Wilson M, Newman H (1999) Oxidative injury and inflammatory periodontal diseases: the challenge of anti-oxidants to free radicals and reactive oxygen species. Crit Rev Oral Biol Med 10:458–476CrossRefPubMedGoogle Scholar
  18. 18.
    Dias-da-Silva MA, Pereira AC, Marin MC, Salgado MA (2013) The influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction in rats. J Clin Exp Dent 5:e169–e173. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Mada EY, Santos AC, Fonseca AC, Biguetti CC, Neves FT, Saraiva PP, Matsumoto MA (2017) Effects of green tea and bisphosphonate association on dental socket repair of rats. Arch Oral Biol 75:1–7. CrossRefPubMedGoogle Scholar
  20. 20.
    Heck CI, de Mejia EG (2007) Yerba Mate Tea (Ilex paraguariensis): a comprehensive review on chemistry, health implications, and technological considerations. J Food Sci 72:R138–R151. CrossRefPubMedGoogle Scholar
  21. 21.
    de Souza LM, Dartora N, Scoparo CT, Cipriani TR, Gorin PA, Iacomini M, Sassaki GL (2011) Comprehensive analysis of maté (Ilex paraguariensis) compounds: development of chemical strategies for matesaponin analysis by mass spectrometry. J Chromatogr A 1218:7307–7315. CrossRefPubMedGoogle Scholar
  22. 22.
    de Morais EC, Stefanuto A, Klein GA, Boaventura BC, de Andrade F, Wazlawik E, Di Pietro PF, Maraschin M, da Silva EL (2009) Consumption of yerba mate ( Ilex paraguariensis ) improves serum lipid parameters in healthy dyslipidemic subjects and provides an additional LDL-cholesterol reduction in individuals on statin therapy. J Agric Food Chem 57:8316–8324. CrossRefPubMedGoogle Scholar
  23. 23.
    Silva RD, Bueno AL, Gallon CW, Gomes LF, Kaiser S, Pavei C, Ortega GG, Kucharski LC, Jahn MP (2011) The effect of aqueous extract of gross and commercial yerba mate (Ilex paraguariensis) on intra-abdominal and epididymal fat and glucose levels in male Wistar rats. Fitoterapia 82:818–826. CrossRefPubMedGoogle Scholar
  24. 24.
    Pereira AA, Tirapeli KG, Neto AH, da Silva BM, da Rocha CQ, Belló-Klein A, Llesuy SF, Dornelles RC, de Melo Stevanato Nakamune AC (2017) Ilex paraguariensis supplementation may be an effective nutritional approach to modulate oxidative stress during perimenopause. Exp Gerontol.
  25. 25.
    Dew TP, Day AJ, Morgan MR (2007) Bone mineral density, polyphenols and caffeine: a reassessment. Nutr Res Rev 20:89–105. CrossRefPubMedGoogle Scholar
  26. 26.
    Pereira CS, Stringhetta-Garcia CT, da Silva Xavier L, Tirapeli KG, Pereira AAF, Kayahara GM, Tramarim JM, Crivelini MM, Padovani KS, Leopoldino AM, Louzada MJQ, Bello-Klein A, Llesuy SF, Ervolino E, Dornelles RCM, Chaves-Neto AH, Nakamune A (2017) Ilex paraguariensis decreases oxidative stress in bone and mitigates the damage in rats during perimenopause. Exp Gerontol 98:148–152. CrossRefPubMedGoogle Scholar
  27. 27.
    Conforti AS, Gallo ME, Saraví FD (2012) Yerba mate (Ilex paraguariensis) consumption is associated with higher bone mineral density in postmenopausal women. Bone 50:9–13. CrossRefPubMedGoogle Scholar
  28. 28.
    Torres T, Farah A (2016) Coffee, maté, açaí and beans are the main contributors to the antioxidant capacity of Brazilian's diet. Eur J Nutr.
  29. 29.
    Matsumoto RL, Bastos DH, Mendonça S, Nunes VS, Bartchewsky W, Ribeiro ML, de Oliveira Carvalho P (2009) Effects of mate tea (Ilex paraguariensis) ingestion on mRNA expression of antioxidant enzymes, lipid peroxidation, and total antioxidant status in healthy young women. J Agric Food Chem 57:1775–1780. CrossRefPubMedGoogle Scholar
  30. 30.
    Matsumoto RL, Mendonca S, de Oliveira DM, Souza MF, Bastos DH (2009) Effects of mate tea intake on ex vivo LDL peroxidation induced by three different pathways. Nutrients 1:18–29. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Suzanne M, Irie K, Glise B, Agnès F, Mori E, Matsumoto K, Noselli S (1999) The drosophila p38 MAPK pathway is required during oogenesis for egg asymmetric development. Genes Dev 13:1464–1474CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Carmo LS, Rogero MM, Cortez M, Yamada M, Jacob PS, Bastos DH, Borelli P, Ambrósio Fock R (2013) The effects of yerba maté (Ilex paraguariensis) consumption on IL-1, IL-6, TNF-α and IL-10 production by bone marrow cells in wistar rats fed a high-fat diet. Int J Vitam Nutr Res 83:26–35. CrossRefPubMedGoogle Scholar
  33. 33.
    Cunha-Correia AS, Neto AH, Pereira AF, Aguiar SM, Nakamune AC (2014) Enteral nutrition feeding alters antioxidant activity in unstimulated whole saliva composition of patients with neurological disorders. Res Dev Disabil 35:1209–1215.
  34. 34.
    Brun LR, Brance ML, Lombarte M, Maher MC, Di Loreto VE, Rigalli A (2015) Effects of yerba mate (IIex paraguariensis) on histomorphometry, biomechanics, and densitometry on bones in the rat. Calcif Tissue Int 97:527–534. CrossRefPubMedGoogle Scholar
  35. 35.
    Guo T, Zhang L, Konermann A, Zhou H, Jin F, Liu W (2015) Manganese superoxide dismutase is required to maintain osteoclast differentiation and function under static force. Sci Rep 5:8016. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Chaves Neto AH, Machado D, Yano CL, Ferreira CV (2011) Antioxidant defense and apoptotic effectors in ascorbic acid and beta-glycerophosphate-induced osteoblastic differentiation. Develop Growth Differ 53:88–96. CrossRefGoogle Scholar
  37. 37.
    Chen CT, Shih YR, Kuo TK, Lee OK, Wei YH (2008) Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells 26:960–968. CrossRefPubMedGoogle Scholar
  38. 38.
    Singleton VL, Orthofer R and Lamuela-Raventós RM (1999) [14] Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Methods in Enzymology. 299 Academic Press, New York, p 152–178Google Scholar
  39. 39.
    Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal Biochem 239:70–76. CrossRefPubMedGoogle Scholar
  40. 40.
    Okamoto T, de Russo MC (1973) Wound healing following tooth extraction. Histochemical study in rats. Rev Fac Odontol Aracatuba 2:153–169PubMedGoogle Scholar
  41. 41.
    Manrique N, Pereira CC, Luvizuto ER, Sanchez Mdel P, Okamoto T, Okamoto R, Sumida DH, Antoniali C (2015) Hypertension modifies OPG, RANK, and RANKL expression during the dental socket bone healing process in spontaneously hypertensive rats. Clin Oral Investig 19:1319–1327. CrossRefPubMedGoogle Scholar
  42. 42.
    Erlebacher A, Filvaroff EH, Ye JQ, Derynck R (1998) Osteoblastic responses to TGF-beta during bone remodeling. Mol Biol Cell 9:1903–1918CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Stringhetta-Garcia CT, Singulani MP, Santos LF, Louzada MJ, Nakamune AC, Chaves-Neto AH, Rossi AC, Ervolino E, Dornelles RC (2016) The effects of strength training and raloxifene on bone health in aging ovariectomized rats. Bone 85:45–54. CrossRefPubMedGoogle Scholar
  44. 44.
    Faria PE, Okamoto R, Bonilha-Neto RM, Xavier SP, Santos AC, Salata LA (2008) Immunohistochemical, tomographic and histological study on onlay iliac grafts remodeling. Clin Oral Implants Res 19:393–401. CrossRefPubMedGoogle Scholar
  45. 45.
    Connerty HV, Briggs AR (1966) Determination of serum calcium by means of orthocresolphthalein complexone. Am J Clin Pathol 45:290–296CrossRefPubMedGoogle Scholar
  46. 46.
    Daly JA, Ertingshausen G (1972) Direct method for determining inorganic phosphate in serum with the “CentrifiChem”. Clin Chem 18:263–265PubMedGoogle Scholar
  47. 47.
    Roy AV (1970) Rapid method for determining alkaline phosphatase activity in serum with thymolphthalein monophosphate. Clin Chem 16:431–436PubMedGoogle Scholar
  48. 48.
    Granjeiro JM, Taga EM, Aoyama H (1997) Purification and characterization of a low-molecular-weight bovine kidney acid phosphatase. An Acad Bras Cienc 69:451–460PubMedGoogle Scholar
  49. 49.
    Janckila AJ, Parthasarathy RN, Parthasarathy LK, Seelan RS, Hsueh YC, Rissanen J, Alatalo SL, Halleen JM, Yam LT (2005) Properties and expression of human tartrate-resistant acid phosphatase isoform 5a by monocyte-derived cells. J Leukoc Biol 77:209–218. CrossRefPubMedGoogle Scholar
  50. 50.
    Laidler PM, Taga EM, Van Etten RL (1982) Human liver acid phosphatases: cysteine residues of the low-molecular-weight enzyme. Arch Biochem Biophys 216:512–521CrossRefPubMedGoogle Scholar
  51. 51.
    Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310CrossRefPubMedGoogle Scholar
  52. 52.
    Arçari DP, Bartchewsky W, dos Santos TW, Oliveira KA, Funck A, Pedrazzoli J, de Souza MF, Saad MJ, Bastos DH, Gambero A, Carvalho PO, Ribeiro ML (2009) Antiobesity effects of yerba maté extract (Ilex paraguariensis) in high-fat diet-induced obese mice. Obesity (Silver Spring) 17:2127–2133. CrossRefGoogle Scholar
  53. 53.
    Lima NS, Franco JG, Peixoto-Silva N, Maia LA, Kaezer A, Felzenszwalb I, de Oliveira E, de Moura EG, Lisboa PC (2014) Ilex paraguariensis (yerba mate) improves endocrine and metabolic disorders in obese rats primed by early weaning. Eur J Nutr 53:73–82. CrossRefGoogle Scholar
  54. 54.
    Scolaro B, Delwing-de Lima D, da Cruz JG, Delwing-Dal Magro D (2012) Mate tea prevents oxidative stress in the blood and hippocampus of rats with acute or chronic ethanol administration. Oxidative Med Cell Longev 2012:314758. CrossRefGoogle Scholar
  55. 55.
    de Oliveira DM, Sampaio GR, Pinto CB, Catharino RR, Bastos DH (2016) Bioavailability of chlorogenic acids in rats after acute ingestion of mate tea (Ilex paraguariensis) or 5-caffeoylquinic acid. Eur J Nutr.
  56. 56.
    Gambero A, Ribeiro ML (2015) The positive effects of yerba mate (Ilex paraguariensis) in obesity. Nutrients 7:730–750. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Arcari DP, Santos JC, Gambero A, Ribeiro ML (2013) The in vitro and in vivo effects of yerba mate (Ilex paraguariensis) extract on adipogenesis. Food Chem 141:809–815. CrossRefPubMedGoogle Scholar
  58. 58.
    Arçari DP, Bartchewsky W, dos Santos TW, Oliveira KA, DeOliveira CC, Gotardo É, Pedrazzoli J, Gambero A, Ferraz LF, Carvalho PO, Ribeiro ML (2011) Anti-inflammatory effects of yerba maté extract (Ilex paraguariensis) ameliorate insulin resistance in mice with high fat diet-induced obesity. Mol Cell Endocrinol 335:110–115. CrossRefPubMedGoogle Scholar
  59. 59.
    Al-Obaidi MM, Al-Bayaty FH, Al Batran R, Hassandarvish P, Rouhollahi E (2014) Protective effect of ellagic acid on healing alveolar bone after tooth extraction in rat—a histological and immunohistochemical study. Arch Oral Biol 59:987–999. CrossRefPubMedGoogle Scholar
  60. 60.
    Tamma R, Colaianni G, Zhu LL, DiBenedetto A, Greco G, Montemurro G, Patano N, Strippoli M, Vergari R, Mancini L, Colucci S, Grano M, Faccio R, Liu X, Li J, Usmani S, Bachar M, Bab I, Nishimori K, Young LJ, Buettner C, Iqbal J, Sun L, Zaidi M, Zallone A (2009) Oxytocin is an anabolic bone hormone. Proc Natl Acad Sci U S A 106:7149–7154. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Iida-Klein A, Zhou H, SS L, Levine LR, Ducayen-Knowles M, Dempster DW, Nieves J, Lindsay R (2002) Anabolic action of parathyroid hormone is skeletal site specific at the tissue and cellular levels in mice. J Bone Miner Res 17:808–816. CrossRefPubMedGoogle Scholar
  62. 62.
    Bixby M, Spieler L, Menini T, Gugliucci A (2005) Ilex paraguariensis extracts are potent inhibitors of nitrosative stress: a comparative study with green tea and wines using a protein nitration model and mammalian cell cytotoxicity. Life Sci 77:345–358. CrossRefPubMedGoogle Scholar
  63. 63.
    Zhang M, Hu X (2016) Mechanism of chlorogenic acid treatment on femoral head necrosis and its protection of osteoblasts. Biomed Rep 5:57–62. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Sassa S, Kikuchi T, Shinoda H, Suzuki S, Kudo H, Sakamoto S (2003) Preventive effect of ferulic acid on bone loss in ovariectomized rats. In: In Vivo, vol 17, pp 277–280Google Scholar
  65. 65.
    García-Martínez O, De Luna-Bertos E, Ramos-Torrecillas J, Ruiz C, Milia E, Lorenzo ML, Jimenez B, Sánchez-Ortiz A, Rivas A (2016) Phenolic compounds in extra virgin olive oil stimulate human osteoblastic cell proliferation. PLoS One 11:e0150045. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Ko CH, Lau KM, Choy WY, Leung PC (2009) Effects of tea catechins, epigallocatechin, gallocatechin, and gallocatechin gallate, on bone metabolism. J Agric Food Chem 57:7293–7297. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Matheus da Silva Brasilino
    • 1
  • Camila Tami Stringhetta-Garcia
    • 2
  • Camila Scacco Pereira
    • 2
  • Ariana Aparecida Ferreira Pereira
    • 2
  • Karina Stringhetta
    • 3
  • Andréia Machado Leopoldino
    • 3
  • Marcelo Macedo Crivelini
    • 4
  • Edilson Ervolino
    • 1
  • Rita Cássia Menegati Dornelles
    • 1
    • 2
  • Ana Cláudia de Melo Stevanato Nakamune
    • 1
    • 2
  • Antonio Hernandes Chaves-Neto
    • 1
    • 2
  1. 1.Department of Basic Sciences, School of DentistrySão Paulo State University (Unesp)AraçatubaBrazil
  2. 2.Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas – SBFis, School of DentistrySão Paulo State University (Unesp)AraçatubaBrazil
  3. 3.Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão PretoUniversity of São Paulo (USP)Ribeirão PretoBrazil
  4. 4.Department of Pathology and Clinical Propaedeutic, School of DentistrySão Paulo State University (Unesp)AraçatubaBrazil

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