Araştırma Makalesi
The Possible Relationship Between Periodontitis and Alzheimer’s Disease and the Beneficial Effects of Salvia Officinalis in an Experimental Rat Model: An İmmunohistochemical Study
Öz
Objective: The present study aimed to investigate potential correlations between Alzheimer's disease (AD) and periodontitis in laboratory rat models with inflammation, the isoform of nitric oxide synthases (iNOS), sclerostin expression, and beneficial effects of Salvia officinalis (S.officinalis).
Material and method: Eighty Wistar albino male rats were randomly divided into equal groups as controls (C), S.officinalis (S), periodontitis (P), and periodontitis+S.officinalis (PS), Alzheimer’s disease (A), Alzheimer’s disease+S.officinalis (AS), Alzheimer’s disease+periodontitis (AP), and Alzheimer’s disease+periodontitis+S.officinalis (APS) groups. While aluminum chloride (AlCl3) and d-galactose (D-gal) were intraperitoneally applied in an AD-like model, S.officinalis extract was administered by oral gavage. Sclerostin and iNOS expressions in periodontal tissues and amyloid-β (Aβ) in the hippocampus were evaluated together.
Results: Alveolar bone loss (ABL) was detected in Groups A and AS (p<0.05). There was no difference in ABL between Groups P and AP (p>0.05). iNOS and sclerostin expressions were detected in Group A. S.officinalis significantly decreased ABL, Aβ, and, in parallel, iNOS and sclerostin expressions in periodontal tissues in Groups PS and APS (p<0.05). The most marked sclerostin expression was observed in Group AP.
Conclusion: Study findings revealed that periodontitis may increase Aβ in AD. Although ABL was not higher in Group AP than in Group P, the increase in iNOS and sclerostin expression in periodontal tissues in Group AP supports the pathogenetic association of AD with periodontitis. S.officinalis may be used as an immunomodulatory aromatic plant in the pathogenetic interaction of periodontal disease and AD.
Anahtar Kelimeler
Alzheimer's disease Periodontitis Salvia Officinalis iNos Sclerostin
Etik Beyan
The present study was carried out under the ethical standards of the research committee of the institution by the 1964 Helsinki Declaration and its later amendments or comparable ethical standards, after the decision of the Süleyman Demirel University Animal Experiments Local Ethics Committee of the university (Approval number: 24/10/2019, 12/03).
Kaynakça
- 1. Gerosa L, Lombardi G. Bone-to-Brain: A round trip in the adaptation to mechanical stimuli. Front Physiol 2021;12:623893
- 2. Cappariello A, Ponzetti M, Rucci N. The “soft” side of the bone: Unveiling its endocrine functions. Horm Mol Biol Clin Investig 2016;28(1):5-20
- 3. Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007;130(3):456-469
- 4. Ross RD, Shah RC, Leurgans S, Bottiglieri T, Wilson RS, Sumner DR. Circulating Dkk1 and TRAIL are associated with cognitive decline in community-dwelling, older adults with cognitive concerns. J Gerontol A Biol Sci Med Sci 2018;73(12):1688-1694
- 5. Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 2005;280(20):19883-19887
- 6. Oliva CA, Montecinos-Oliva C, Inestrosa NC. Wnt signaling in the central nervous system: New insights in health and disease. Prog Mol Biol Transl Sci 2018;153:81-130
- 7. Bateman RJ, Aisen PS, De Strooper B, et al. Autosomal-dominant Alzheimer’s disease: A review and proposal for the prevention of Alzheimer’s disease. Alzheimer's Res Ther 2011;3(1):1
- 8. Holmer J, Eriksdotter M, Schultzberg M, Pussinen PJ, Buhlin K. Association between periodontitis and risk of Alzheimer’s disease, mild cognitive impairment, and subjective cognitive decline: A case-control study. J Clin Periodontol 2018;45(11):1287-1298
- 9. Chapple ILC, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000 2007;43(1):160-232
- 10. Lappin DF, Kjeldsen M, Sander L, Kinane DF. Inducible nitric oxide synthase expression in periodontitis. J Periodontal Res 2000;35(6):369-373
- 11. Li TJ, Wang R, Li QY, Li CY, Jiang L, Guo LS. Sclerostin regulation: A promising therapy for periodontitis by modulating alveolar bone. Chin Med J (Engl) 2020;133(12):1456-1461
- 12. Mendes FSF, Garcia LM, Moraes T da S, et al. Antibacterial activity of Salvia Officinalis L. against periodontopathogens: An in vitro study. Anaerobe 2020;63:102194
- 13. Jiang P, Li C, Xiang Z, Jiao B. Tanshinone IIA reduces the risk of Alzheimer’s disease by inhibiting iNOS, MMP 2, and NF κBp65 transcription and translation in the temporal lobes of rat models of Alzheimer’s disease. Mol Med Rep 2014;10(2):689-694
- 14. Bilgic Y, Demir EA, Bilgic N, Dogan H, Tutuk O, Tumer C. Detrimental effects of chia (Salvia hispanica L.) seeds on learning and memory in aluminum chloride-induced experimental Alzheimer's disease. Acta Neurobiol Exp (Wars) 2018;78(4):322-331. PMID:30624431
- 15. De Lima V, Bezerra MM, De Menezes Alencar VB, et al. Effects of chlorpromazine on alveolar bone loss in experimental periodontal disease in rats. Eur J Oral Sci 2000;108(2):123-129
- 16. Toker H, Yuce HB, Yildirim A, Tekin MB, Gevrek F. The effect of colchicine on alveolar bone loss in ligature-induced periodontitis. Braz Oral Res 2019;33:e001
- 17. de Molon RS, de Avila ED, Nogueira AVB, de Souza AJC, Avila-Campos MJ, de Andrade CR, Cirelli JA. Evaluation of the host response in various models of induced periodontal disease in mice. J Periodontol 2014;85(3):465-477
- 18. Toker H, Ozdemir H, Eren K, Ozer H, Sahın G. N-acetylcysteine, a thiol antioxidant, decreases alveolar bone loss in experimental periodontitis in rats. J Periodontol 2009;80(4):672-678
- 19. de Molon RS, Park CH, Jin Q, Sugai J, Cirelli JA. Characterization of ligature-induced experimental periodontitis. Microsc Res Tech 2018;81(12):1412-1421
- 20. Yiğit U, Kırzıoğlu FY, Uğuz AC, Nazıroğlu M, Özmen Ö. Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis? Arch Oral Biol 2017;81:61-68
- 21. Xiao F, Li XG, Zhang XY, et al. Combined administration of D-galactose and aluminum induces Alzheimer-like lesions in the brain. Neurosci Bull 2011;27(3):143-155
- 22. Yang W, Shi L, Chen L, et al. Protective effects of perindopril on d-galactose and aluminum trichloride induced neurotoxicity via the apoptosis of mitochondrial-mediated intrinsic pathway in the hippocampus of mice. Brain Res Bull 2014;109:46-53
- 23. Dugger BN, Dickson DW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 2017;9(7):a028035
- 24. Deture MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener 2019;14(1):32
- 25. Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJ. Inflammation and Alzheimer’s disease: Possible role of periodontal diseases. Alzheimer's Dement 2008;4(4):242-250
- 26. Chen CK, Wu YT, Chang YC. Association between chronic periodontitis and the risk of Alzheimer’s disease: A retrospective, population-based, matched cohort study. Alzheimer's Res Ther 2017;9(1):56
- 27. Kamer AR, Pirraglia E, Tsui W, et al. Periodontal disease is associated with higher brain amyloid load in normal elderly. Neurobiol Aging 2015;36(2):627-633
- 28. Kantarci A, Tognoni CM, Yaghmoor W, et al. Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease. Sci Rep 2020;10(1):18561
- 29. Ishida N, Ishihara Y, Ishida K, et al. Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice. NPJ Aging Mech Dis 2017;3(1):15
- 30. Ghorbani A, Esmaeilizadeh M. Pharmacological properties of Salvia officinalis and its components. J Tradit Complement Med 2017;7(4):433-440
- 31. Kontogianni VG, Tomic G, Nikolic I, et al. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chem 2013;136(1):120-129
- 32. Kolac UK, Ustuner MC, Tekin N, Ustuner D, Colak E, Entok E. The Anti-Inflammatory and antioxidant effects of salvia officinalis on lipopolysaccharide-induced inflammation in rats. J Med Food 2017;20(12):1193-1200 33. Kostić M, Kitić D, Petrović MB, et al. Anti-inflammatory effect of the Salvia sclarea L. ethanolic extract on lipopolysaccharide-induced periodontitis in rats. J Ethnopharmacol 2017;199:52-59
- 34. Tsai HT, Chang WL, Tu HP, Fu E, Hsieh YD, Chiang CY. Effects of Salvia miltiorrhiza ethanolic extract on lipopolysaccharide-induced dental alveolar bone resorption in rats. J Dent Sci 2016;11(1):35-40
- 35. Leitão RFC, Ribeiro RA, Chaves HV, Rocha FAC, Lima V, Brito GAC. Nitric oxide synthase inhibition prevents alveolar bone resorption in experimental periodontitis in rats. J Periodontol 2005;76(6):956-963
- 36. Pan Z, Guzeldemir E, Toygar HU, Bal N, Bulut S. Nitric oxide synthase in gingival tissues of patients with chronic periodontitis and with and without diabetes. J Periodontol 2010;81(1):109-120
- 37. Lohinai Z, Benedek P, Fehér E, et al. Protective effects of mercapto-ethyl guanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. Br J Pharmacol 1998;123(3):353-360
- 38. Steinert JR, Chernova T, Forsythe ID. Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist 2010;16(4):435-452
- 39. Haas J, Storch-Hagenlocher B, Biessmann A, Wildemann B. Inducible nitric oxide synthase and argininosuccinate synthetase: co-induction in brain tissue of patients with Alzheimer’s dementia and following stimulation with beta-amyloid 1-42 in vitro. Neurosci Lett 2002;322(2):121-125
- 40. Grancieri M, Martino HSD, Gonzalez de Mejia E. Digested total protein and protein fractions from chia seed (Salvia hispanica L. ) had high scavenging capacity and inhibited 5-LOX, COX-1-2, and iNOS enzymes. Food Chem 2019;289:204-214
- 41. Ominsky MS, Vlasseros F, Jolette J, et al. Two doses of sclerostin antibody in cynomolgus monkeys increase bone formation, bone mineral density, and bone strength. J Bone Miner Res 2010;25(5):948-959
- 42. Tamplen M, Fowler T, Markey J, Knott PD, Suva LJ, Alliston T. Treatment with anti-Sclerostin antibody to stimulate mandibular bone formation. Head Neck 2018;40(7):1453-1460
Yıl 2025,
Cilt: 32 Sayı: 2, 111 - 120, 19.06.2025
Öz
Kaynakça
- 1. Gerosa L, Lombardi G. Bone-to-Brain: A round trip in the adaptation to mechanical stimuli. Front Physiol 2021;12:623893
- 2. Cappariello A, Ponzetti M, Rucci N. The “soft” side of the bone: Unveiling its endocrine functions. Horm Mol Biol Clin Investig 2016;28(1):5-20
- 3. Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007;130(3):456-469
- 4. Ross RD, Shah RC, Leurgans S, Bottiglieri T, Wilson RS, Sumner DR. Circulating Dkk1 and TRAIL are associated with cognitive decline in community-dwelling, older adults with cognitive concerns. J Gerontol A Biol Sci Med Sci 2018;73(12):1688-1694
- 5. Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 2005;280(20):19883-19887
- 6. Oliva CA, Montecinos-Oliva C, Inestrosa NC. Wnt signaling in the central nervous system: New insights in health and disease. Prog Mol Biol Transl Sci 2018;153:81-130
- 7. Bateman RJ, Aisen PS, De Strooper B, et al. Autosomal-dominant Alzheimer’s disease: A review and proposal for the prevention of Alzheimer’s disease. Alzheimer's Res Ther 2011;3(1):1
- 8. Holmer J, Eriksdotter M, Schultzberg M, Pussinen PJ, Buhlin K. Association between periodontitis and risk of Alzheimer’s disease, mild cognitive impairment, and subjective cognitive decline: A case-control study. J Clin Periodontol 2018;45(11):1287-1298
- 9. Chapple ILC, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000 2007;43(1):160-232
- 10. Lappin DF, Kjeldsen M, Sander L, Kinane DF. Inducible nitric oxide synthase expression in periodontitis. J Periodontal Res 2000;35(6):369-373
- 11. Li TJ, Wang R, Li QY, Li CY, Jiang L, Guo LS. Sclerostin regulation: A promising therapy for periodontitis by modulating alveolar bone. Chin Med J (Engl) 2020;133(12):1456-1461
- 12. Mendes FSF, Garcia LM, Moraes T da S, et al. Antibacterial activity of Salvia Officinalis L. against periodontopathogens: An in vitro study. Anaerobe 2020;63:102194
- 13. Jiang P, Li C, Xiang Z, Jiao B. Tanshinone IIA reduces the risk of Alzheimer’s disease by inhibiting iNOS, MMP 2, and NF κBp65 transcription and translation in the temporal lobes of rat models of Alzheimer’s disease. Mol Med Rep 2014;10(2):689-694
- 14. Bilgic Y, Demir EA, Bilgic N, Dogan H, Tutuk O, Tumer C. Detrimental effects of chia (Salvia hispanica L.) seeds on learning and memory in aluminum chloride-induced experimental Alzheimer's disease. Acta Neurobiol Exp (Wars) 2018;78(4):322-331. PMID:30624431
- 15. De Lima V, Bezerra MM, De Menezes Alencar VB, et al. Effects of chlorpromazine on alveolar bone loss in experimental periodontal disease in rats. Eur J Oral Sci 2000;108(2):123-129
- 16. Toker H, Yuce HB, Yildirim A, Tekin MB, Gevrek F. The effect of colchicine on alveolar bone loss in ligature-induced periodontitis. Braz Oral Res 2019;33:e001
- 17. de Molon RS, de Avila ED, Nogueira AVB, de Souza AJC, Avila-Campos MJ, de Andrade CR, Cirelli JA. Evaluation of the host response in various models of induced periodontal disease in mice. J Periodontol 2014;85(3):465-477
- 18. Toker H, Ozdemir H, Eren K, Ozer H, Sahın G. N-acetylcysteine, a thiol antioxidant, decreases alveolar bone loss in experimental periodontitis in rats. J Periodontol 2009;80(4):672-678
- 19. de Molon RS, Park CH, Jin Q, Sugai J, Cirelli JA. Characterization of ligature-induced experimental periodontitis. Microsc Res Tech 2018;81(12):1412-1421
- 20. Yiğit U, Kırzıoğlu FY, Uğuz AC, Nazıroğlu M, Özmen Ö. Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis? Arch Oral Biol 2017;81:61-68
- 21. Xiao F, Li XG, Zhang XY, et al. Combined administration of D-galactose and aluminum induces Alzheimer-like lesions in the brain. Neurosci Bull 2011;27(3):143-155
- 22. Yang W, Shi L, Chen L, et al. Protective effects of perindopril on d-galactose and aluminum trichloride induced neurotoxicity via the apoptosis of mitochondrial-mediated intrinsic pathway in the hippocampus of mice. Brain Res Bull 2014;109:46-53
- 23. Dugger BN, Dickson DW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 2017;9(7):a028035
- 24. Deture MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener 2019;14(1):32
- 25. Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJ. Inflammation and Alzheimer’s disease: Possible role of periodontal diseases. Alzheimer's Dement 2008;4(4):242-250
- 26. Chen CK, Wu YT, Chang YC. Association between chronic periodontitis and the risk of Alzheimer’s disease: A retrospective, population-based, matched cohort study. Alzheimer's Res Ther 2017;9(1):56
- 27. Kamer AR, Pirraglia E, Tsui W, et al. Periodontal disease is associated with higher brain amyloid load in normal elderly. Neurobiol Aging 2015;36(2):627-633
- 28. Kantarci A, Tognoni CM, Yaghmoor W, et al. Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease. Sci Rep 2020;10(1):18561
- 29. Ishida N, Ishihara Y, Ishida K, et al. Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice. NPJ Aging Mech Dis 2017;3(1):15
- 30. Ghorbani A, Esmaeilizadeh M. Pharmacological properties of Salvia officinalis and its components. J Tradit Complement Med 2017;7(4):433-440
- 31. Kontogianni VG, Tomic G, Nikolic I, et al. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chem 2013;136(1):120-129
- 32. Kolac UK, Ustuner MC, Tekin N, Ustuner D, Colak E, Entok E. The Anti-Inflammatory and antioxidant effects of salvia officinalis on lipopolysaccharide-induced inflammation in rats. J Med Food 2017;20(12):1193-1200 33. Kostić M, Kitić D, Petrović MB, et al. Anti-inflammatory effect of the Salvia sclarea L. ethanolic extract on lipopolysaccharide-induced periodontitis in rats. J Ethnopharmacol 2017;199:52-59
- 34. Tsai HT, Chang WL, Tu HP, Fu E, Hsieh YD, Chiang CY. Effects of Salvia miltiorrhiza ethanolic extract on lipopolysaccharide-induced dental alveolar bone resorption in rats. J Dent Sci 2016;11(1):35-40
- 35. Leitão RFC, Ribeiro RA, Chaves HV, Rocha FAC, Lima V, Brito GAC. Nitric oxide synthase inhibition prevents alveolar bone resorption in experimental periodontitis in rats. J Periodontol 2005;76(6):956-963
- 36. Pan Z, Guzeldemir E, Toygar HU, Bal N, Bulut S. Nitric oxide synthase in gingival tissues of patients with chronic periodontitis and with and without diabetes. J Periodontol 2010;81(1):109-120
- 37. Lohinai Z, Benedek P, Fehér E, et al. Protective effects of mercapto-ethyl guanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. Br J Pharmacol 1998;123(3):353-360
- 38. Steinert JR, Chernova T, Forsythe ID. Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist 2010;16(4):435-452
- 39. Haas J, Storch-Hagenlocher B, Biessmann A, Wildemann B. Inducible nitric oxide synthase and argininosuccinate synthetase: co-induction in brain tissue of patients with Alzheimer’s dementia and following stimulation with beta-amyloid 1-42 in vitro. Neurosci Lett 2002;322(2):121-125
- 40. Grancieri M, Martino HSD, Gonzalez de Mejia E. Digested total protein and protein fractions from chia seed (Salvia hispanica L. ) had high scavenging capacity and inhibited 5-LOX, COX-1-2, and iNOS enzymes. Food Chem 2019;289:204-214
- 41. Ominsky MS, Vlasseros F, Jolette J, et al. Two doses of sclerostin antibody in cynomolgus monkeys increase bone formation, bone mineral density, and bone strength. J Bone Miner Res 2010;25(5):948-959
- 42. Tamplen M, Fowler T, Markey J, Knott PD, Suva LJ, Alliston T. Treatment with anti-Sclerostin antibody to stimulate mandibular bone formation. Head Neck 2018;40(7):1453-1460
Toplam 41 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Periodontoloji |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 19 Haziran 2025 |
| Gönderilme Tarihi | 28 Ağustos 2024 |
| Kabul Tarihi | 29 Nisan 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 32 Sayı: 2 |
Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi/Medical Journal of Süleyman Demirel University is licensed under Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International.