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New bone-generative effect of Salvia officinalis L. in the expanded midpalatal suture

An in vivo and in vitro study

Knochenneubildende Wirkung von Salvia officinalis L. in der erweiterten prämaxillären Naht

Eine In-vivo- und In-vitro-Studie

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Abstract

Purpose

The aims of this study were to evaluate the effects of systemic administration of Salvia officinalis Linnaeus (L.) leaf extract on new bone formation in the expanded premaxillary suture in rats in vivo and to examine the antioxidant effects and phenolic profile of Salvia officinalis (SO) leaf and root extracts in vitro.

Methods

Fourteen male Sprague Dawley rats were allocated to two groups: SO group (n = 7) and control group (n = 7). An open-loop spring was attached to the upper incisors of each rat to expand the premaxillae. A 5-day expansion period followed by a 12-day retention period was observed. The rats in the SO group received systemic administration of 20 mg SO/kg/day via the orogastric route for 17 days. Histomorphometric examinations were carried out to examine the amount of new bone formation, number of capillaries, and intensity of inflammatory cell response. Immunohistochemical analysis was conducted to examine the number of osteoblasts and osteoclasts. Leaf and root extracts of SO were also analyzed for antioxidant activity and phenolic compounds in vitro.

Results

Statistical analysis showed that the following were higher in the SO group than in the control group: new bone formation, number of osteoblasts and osteoclasts, intensity of inflammatory cell response (neutrophils, lymphocytes, and macrophages), and number of capillaries. The major compound identified in SO leaf extract was rosmarinic acid, while luteolin derivatives, salvianolic acid F, and medioresinol were also present.

Conclusions

Salvia officinalis L. from leaf extract provided antioxidant effects and stimulated enhanced new bone formation in the expanded midpalatal suture after maxillary expansion in rats.

Zusammenfassung

Zielsetzung

Ziele dieser Studie waren die Bewertung der Auswirkungen einer systemischen Verabreichung von Salvia officinalis Linnaeus (L.) auf die Knochenneubildung in der erweiterten prämaxillären Naht bei Ratten unter In-vivo-Bedingungen sowie die Untersuchung der antioxidativen Wirkungen und des phenolischen Profils von Salvia officinalis(SO)-Extrakten unter In-vitro-Bedingungen.

Methoden

Vierzehn männliche Sprague-Dawley-Ratten wurden 2 Gruppen zugeordnet: SO- (n = 7) und Kontrollgruppe (n = 7). An den oberen Schneidezähnen jeder Ratte wurde eine offene Feder zur prämaxillären Erweiterung angebracht. Untersucht wurden eine 5‑tägige Expansionsperiode, gefolgt von einer 12-tägigen Retentionsdauer. Den Ratten in der SO-Gruppe wurde 17 Tage lang 20 mg SO/kg/Tag über eine orogastrale Sonde verabreicht. Histomorphometrische Untersuchungen wurden durchgeführt, um die Menge der Knochenneubildung, die Anzahl der Kapillaren und die Intensität der Entzündungszellen zu ermitteln, ferner eine immunhistochemische Analyse, um die Anzahl der Osteoblasten und Osteoklasten zu bestimmen. Blatt- und Wurzelextrakte von SO wurden zudem in vitro auf antioxidative Aktivität und phenolische Verbindungen analysiert.

Ergebnisse

Die statistische Analyse hat gezeigt, dass die Knochenneubildung, die Anzahl der Osteoblasten und Osteoklasten, die Intensität der Entzündungszellen sowie die Anzahl der Kapillaren in der SO-Gruppe höher waren als in der Kontrollgruppe. Die wichtigste im SO-Blattextrakt identifizierte Verbindung war Rosmarinsäure, zusätzlich waren Luteolinderivate, Salvianolsäure F und Medioresinol nachweisbar.

Schlussfolgerung

Der Salvia-officinalis-L.-Blattextrakt hatte antioxidative Wirkungen und stimulierte die erhöhte Knochenneubildung in der erweiterten mittleren Gaumennaht nach Expansion des Oberkiefers bei Ratten.

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Abbreviations

ABTS:

2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)

BHT:

Butylated hydroxytoluene

DPPH:

2,2-diphenyl-1-picrylhydrazyl

EDTA:

Ethylenediamine tetra-acetic acid

HPLC:

High-performance liquid chromatography

IC50 :

50% inhibitory concentration

LC-MS/MS:

Liquid chromatography with tandem mass spectrometry

RME:

Rapid maxillary expansion

SO:

Salvia officinalis

TEAC:

Trolox equivalent antioxidant capacity

References

  1. Bishara SE, Staley RN (1987) Maxillary expansion: clinical implications. Am J Orthod Dentofacial Orthop 91:3–14

    Article  PubMed  Google Scholar 

  2. Altan BA, Kara IM, Nalcaci R, Ozan F, Erdogan SM, Ozkut MM et al (2013) Systemic propolis stimulates new bone formation at the expanded suture: a histomorphometric study. Angle Orthod 83:286–291

    Article  PubMed  Google Scholar 

  3. Kara MI, Altan AB, Sezer U, Erdogan MS, Inan S, Ozkut M et al (2012) Effects of Ginkgo biloba on experimental rapid maxillary expansion model: a histomorphometric study. Oral Surg Oral Med Oral Pathol Oral Radiol 114:712–718

    Article  PubMed  Google Scholar 

  4. Kara MI, Erciyas K, Altan AB, Ozkut M, Ay S, Inan S (2012) Thymoquinone accelerates new bone formation in the rapid maxillary expansion procedure. Arch Oral Biol 57:357–363

    Article  PubMed  Google Scholar 

  5. Uysal T, Amasyali M, Olmez H, Enhos S, Karslioglu Y, Gunhan O (2011) Effect of vitamin C on bone formation in the expanded inter-premaxillary suture. Early bone changes. J Orofac Orthop 72:290–300

    Article  PubMed  Google Scholar 

  6. Uysal T, Gorgulu S, Yagci A, Karslioglu Y, Gunhan O, Sagdic D (2011) Effect of resveratrol on bone formation in the expanded inter-premaxillary suture: early bone changes. Orthod Craniofac Res 14:80–87

    Article  PubMed  Google Scholar 

  7. Halicioglu K, Corekci B, Akkas I, Irgin C, Ozan F, Yilmaz F et al (2015) Effect of St John’s wort on bone formation in the orthopaedically expanded premaxillary suture in rats: a histological study. Eur J Orthod 37:164–169

    Article  PubMed  Google Scholar 

  8. Kazancioglu HO, Aksakalli S, Ezirganli S, Birlik M, Esrefoglu M, Acar AH (2015) Effect of caffeic acid phenethyl ester on bone formation in the expanded inter-premaxillary suture. Drug Des Devel Ther 9:6483–6488

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cheng Y, Lv C, Li T, Zhang C, Li R, Tao G et al (2020) Palatal expansion and relapse in rats: a histologic and immunohistochemical study. Am J Orthod Dentofacial Orthop 157:783–791

    Article  PubMed  Google Scholar 

  10. Gibon E, Lu LY, Nathan K, Goodman SB (2017) Inflammation, ageing, and bone regeneration. J Orthop Translat 10:28–35

    Article  PubMed  PubMed Central  Google Scholar 

  11. Giannoudis PV, Hak D, Sanders D, Donohoe E, Tosounidis T, Bahney C (2015) Inflammation, bone healing, and anti-inflammatory drugs: an update. J Orthop Trauma 29(12):S6–9

    Article  PubMed  Google Scholar 

  12. Hamidpour M, Hamidpour R, Hamidpour S, Shahlari M (2014) Chemistry, pharmacology, and medicinal property of sage (salvia) to prevent and cure illnesses such as obesity, diabetes, depression, dementia, lupus, autism, heart disease, and cancer. J Tradit Complement Med 4:82–88

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kot B, Wierzchowska K, Piechota M, Czerniewicz P, Chrzanowski G (2019) Antimicrobial activity of five essential oils from lamiaceae against multidrug-resistant staphylococcus aureus. Nat Prod Res 33:3587–3591

    Article  PubMed  Google Scholar 

  14. Miura K, Kikuzaki H, Nakatani N (2002) Antioxidant activity of chemical components from sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.) measured by the oil stability index method. J Agric Food Chem 50:1845–1851

    Article  PubMed  Google Scholar 

  15. Matsingou TC, Petrakis N, Kapsokefalou M, Salifoglou A (2003) Antioxidant activity of organic extracts from aqueous infusions of sage. J Agric Food Chem 51:6696–6701

    Article  PubMed  Google Scholar 

  16. Park JB (2011) Identification and quantification of a major anti-oxidant and anti-inflammatory phenolic compound found in basil, lemon thyme, mint, oregano, rosemary, sage, and thyme. Int J Food Sci Nutr 62:577–584

    Article  PubMed  Google Scholar 

  17. Bakota EL, Winkler-Moser JK, Berhow MA, Eller FJ, Vaughn SF (2015) Antioxidant activity and sensory evaluation of a rosmarinic acid-enriched extract of Salvia officinalis. J Food Sci 80:C711–7

    Article  PubMed  Google Scholar 

  18. Shi W, Fu S, Du N (2000) Effect of effective fraction of Radix Salviae Miltiorrhizae on procollagen gene expression in fracture healing. Zhongguo Zhong Xi Yi Jie He Za Zhi 20:269–271

    PubMed  Google Scholar 

  19. Muhlbauer RC, Lozano A, Palacio S, Reinli A, Felix R (2003) Common herbs, essential oils, and monoterpenes potently modulate bone metabolism. Bone 32:372–380

    Article  PubMed  Google Scholar 

  20. Putnam SE, Scutt AM, Bicknell K, Priestley CM, Williamson EM (2007) Natural products as alternative treatments for metabolic bone disorders and for maintenance of bone health. Phytother Res 21:99–112

    Article  PubMed  Google Scholar 

  21. He X, Shen Q (2014) Salvianolic acid B promotes bone formation by increasing activity of alkaline phosphatase in a rat tibia fracture model: a pilot study. BMC Complement Altern Med 14:493

    Article  PubMed  PubMed Central  Google Scholar 

  22. Spiridonov NA, Arkhipov VV, Foigel AG, Shipulina LD, Fomkina MG (2003) Protonophoric and uncoupling activity of royleanones from Salvia officinalis and euvimals from Eucalyptus viminalis. Phytother Res 17:1228–1230

    Article  PubMed  Google Scholar 

  23. Davis PH, Cullen J, Coode MJE (1965) Flora of Turkey and the East Aegean Islands. University Press, Edinburgh

    Google Scholar 

  24. Singleton VL, Orthofer R, Lamuela-Raventós RM (1999) Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent methods in enzymology. Elsevier, pp 152–178

    Google Scholar 

  25. Brand-Williams W, Cuvelier M‑E, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT - Food Sci Technol 28:25–30

    Article  Google Scholar 

  26. Velioglu Y, Mazza G, Gao L, Oomah BD (1998) Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. J Agric Food Chem 46:4113–4117

    Article  Google Scholar 

  27. Papandreou MA, Kanakis CD, Polissiou MG, Efthimiopoulos S, Cordopatis P, Margarity M et al (2006) Inhibitory activity on amyloid‑β aggregation and antioxidant properties of crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem 54:8762–8768

    Article  PubMed  Google Scholar 

  28. Deynek GT, Ramoglu SI (2019) Effects of different settings for 940 nm diode laser on expanded suture in rats. Angle Orthod 89:446–454

    Article  Google Scholar 

  29. Sawada M, Shimizu N (1996) Stimulation of bone formation in the expanding mid-palatal suture by transforming growth factor-beta 1 in the rat. Eur J Orthod 18:169–179

    PubMed  Google Scholar 

  30. Birlik M, Babacan H, Cevit R, Gurler B (2016) Effect of sex steroids on bone formation in an orthopedically expanded suture in rats : an immunohistochemical and computed tomography study. J Orofac Orthop 77:94–103

    Article  PubMed  Google Scholar 

  31. Nascimento MF, Almeida BM, Cunha JL, Valois RB, Pinheiro JC, Ribeiro MA et al (2015) Improvement of bone repair in diabetic rats subjected to 780 nm low-level laser therapy. Acta Cir Bras 30:660–667

    Article  PubMed  Google Scholar 

  32. Chen H, Zhang Q, Wang XM, Yang J, Wang Q (2011) Qualitative analysis and simultaneous quantification of phenolic compounds in the aerial parts of salvia miltiorrhiza by HPLC-DAD and ESI/Msn. Phytochem Anal 22:247–257

    Article  PubMed  Google Scholar 

  33. Kontogianni VG, Tomic G, Nikolic I, Nerantzaki AA, Sayyad N, Stosic-Grujicic S et al (2013) Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chem 136:120–129

    Article  PubMed  Google Scholar 

  34. Cvetkovikj I, Stefkov G, Acevska J, Stanoeva JP, Karapandzova M, Stefova M et al (2013) Polyphenolic characterization and chromatographic methods for fast assessment of culinary Salvia species from South East Europe. J Chromatogr A 1282:38–45

    Article  PubMed  Google Scholar 

  35. Mena P, Cirlini M, Tassotti M, Herrlinger KA, Dall’Asta C, Del Rio D (2016) Phytochemical profiling of flavonoids, phenolic acids, terpenoids, and volatile fraction of a rosemary (Rosmarinus officinalis L.) extract. Molecules 21:1576

    Article  PubMed Central  Google Scholar 

  36. Irgin C, Corekci B, Ozan F, Halicioglu K, Toptas O, Birinci Yildirim A et al (2016) Does stinging nettle (Urtica dioica) have an effect on bone formation in the expanded inter-premaxillary suture? Arch Oral Biol 69:13–18

    Article  PubMed  Google Scholar 

  37. Cheng Y, Sun J, Zhou Z, Pan J, Zou S, Chen J (2018) Effects of lactoferrin on bone resorption of midpalatal suture during rapid expansion in rats. Am J Orthod Dentofacial Orthop 154:115–127

    Article  PubMed  Google Scholar 

  38. Fitts DA (2011) Ethics and animal numbers: informal analyses, uncertain sample sizes, inefficient replications, and type I errors. J Am Assoc Lab Anim Sci 50:445–453

    PubMed  PubMed Central  Google Scholar 

  39. Elkomy MM, Elsaid FG (2015) Anti-osteoporotic effect of medical herbs and calcium supplementation on ovariectomized rats. J Basic Appl Zool 72:81–88

    Article  Google Scholar 

  40. Azmy Abd El-Motelp B, Tarek Ebrahim M, Khairy Mohamed H (2021) Salvia officinalis extract and 17beta-estradiol suppresses ovariectomy induced osteoporosis in female rats. Pak J Biol Sci 24:434–444

    Article  PubMed  Google Scholar 

  41. Boyce BF, Yao Z, Xing L (2009) Osteoclasts have multiple roles in bone in addition to bone resorption. Crit Rev Eukaryot Gene Expr 19:171–180

    Article  PubMed  PubMed Central  Google Scholar 

  42. Azevedo MI, Pereira AF, Nogueira RB, Rolim FE, Brito GA, Wong DV et al (2013) The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy. Mol Pain 9:53

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lee JW, Asai M, Jeon SK, Iimura T, Yonezawa T, Cha BY et al (2015) Rosmarinic acid exerts an antiosteoporotic effect in the RANKL-induced mouse model of bone loss by promotion of osteoblastic differentiation and inhibition of osteoclastic differentiation. Mol Nutr Food Res 59:386–400

    Article  PubMed  Google Scholar 

  44. Kim MY, Bo HH, Choi EO, Kwon DH, Kim HJ, Ahn KI et al (2018) Induction of apoptosis by citrus unshiu peel in human breast cancer MCF‑7 cells: involvement of ROS-dependent activation of AMPK. Biol Pharm Bull 41:713–721

    Article  PubMed  Google Scholar 

  45. Xu Y, Jiang Z, Ji G, Liu J (2010) Inhibition of bone metastasis from breast carcinoma by rosmarinic acid. Planta Med 76:956–962

    Article  PubMed  Google Scholar 

  46. Jeong MJ, Lim DS, Kim SO, Park C, Choi YH, Jeong SJ (2021) Effect of rosmarinic acid on differentiation and mineralization of MC3T3-E1 osteoblastic cells on titanium surface. Anim Cells Syst (Seoul) 25:46–55

    Article  Google Scholar 

  47. Kim TH, Jung JW, Ha BG, Hong JM, Park EK, Kim HJ et al (2011) The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss. J Nutr Biochem 22:8–15

    Article  PubMed  Google Scholar 

  48. Xagorari A, Papapetropoulos A, Mauromatis A, Economou M, Fotsis T, Roussos C (2001) Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Ther 296:181–187

    PubMed  Google Scholar 

  49. Choi EM (2007) Modulatory effects of luteolin on osteoblastic function and inflammatory mediators in osteoblastic MC3T3-E1 cells. Cell Biol Int 31:870–877

    Article  PubMed  Google Scholar 

  50. Zhang J, Ahn MJ, Sun QS, Kim KY, Hwang YH, Ryu JM et al (2008) Inhibitors of bone resorption from Halenia corniculata. Arch Pharm Res 31:850–855

    Article  PubMed  Google Scholar 

  51. Dias MI, Barros L, Alves RC, Oliveira MBP, Santos-Buelga C, Ferreira IC. (2014). Nutritional composition, antioxidant activity and phenolic compounds of wild Taraxacum sect. Ruderalia. Food Res Int 56:266–271

    Article  Google Scholar 

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Funding

This study was supported by the Scientific Research Projects Commission (BAP) of Anadolu University (Eskisehir, Turkey; project number 1701S029).

Author information

Authors and Affiliations

  1. Department of Orthodontics, Faculty of Dentistry, Istanbul Aydin University, 34295, Florya, Istanbul, Turkey

    Emre Kayalar PhD, DDS, MPharm

  2. Discipline of Orthodontics and Paediatric Dentistry, School of Dentistry, The University of Sydney, Sydney Dental Hospital, Surry Hills, Australia

    Emre Kayalar PhD, DDS, MPharm

  3. Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey

    Fatih Goger PhD, MPharm

  4. Private Practice, Istanbul, Turkey

    Gul Tas Deynek PhD, DDS

  5. Department of Histology and Embryology, Faculty of Medicine, Regenerative and Restorative Medicine Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey

    Olgu Enis Tok PhD

  6. Department of Pharmaceutical Botany, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey

    Emre Kayalar PhD, DDS, MPharm &  Sevim Kucuk PhD, MPharm

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  1. Emre Kayalar PhD, DDS, MPharm
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  2. Fatih Goger PhD, MPharm
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  3. Gul Tas Deynek PhD, DDS
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All authors read and approved the submitted version.

Corresponding author

Correspondence to Emre Kayalar PhD, DDS, MPharm.

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Conflict of interest

E. Kayalar, F. Goger, G. Tas Deynek, O.E. Tok and S. Kucuk declare that they have no competing interests.

Ethical standards

The animal experimental protocol in this study was approved by the Bezmialem Foundation University Institutional Review Board and Animal Use Committee (protocol no.: 2016/110). Consent for publication: Not applicable. Consent to participate: Not applicable.

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Kayalar, E., Goger, F., Tas Deynek, G. et al. New bone-generative effect of Salvia officinalis L. in the expanded midpalatal suture. J Orofac Orthop 83 (Suppl 1), 85–95 (2022). https://doi.org/10.1007/s00056-021-00366-3

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