Effects of aloe-emodin on alveolar bone in Porphyromonas gingivalis-induced periodontitis rat model: a pilot study
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Aloe-emodin (AE), a natural anthraquinone abundant in aloe plants and rhubarb (Rheum rhabarbarum), has long been used to treat chronic inflammatory diseases. However, AE’s underlying mechanisms in periodontal inflammation have not been fully elucidated. Acidic mammalian chitinase (AMCase) is a potential biomarker involved in bone remodeling. This study aimed to evaluate AE’s effect on periodontitis in rats and investigate AMCase expression. Methods: Eighteen Sprague-Dawley rats were separated into the following groups: healthy (group 1), disease (group 2), vehicle (group 3), AE high-dose (group 4), and AE low-dose (group 5). Porphyromonas gingivalis ligatures were placed in rats (groups 2–5) for 7 days. Groups 4 and 5 were then treated with AE for an additional 14 days. Saliva was collected from all groups, and probing pocket depth was measured in succession. Periodontal pocket tissues were subjected to histomorphometric analysis after the rats were sacrificed. Bone marrowderived macrophages and murine macrophages were stimulated with receptor activator of nuclear factor-κB ligand (RANKL) and treated with different concentrations of AE. AMCase expression was detected from the analysis of saliva, periodontal pocket tissues, and differentiated osteoclasts. Results: Among rats with P. gingivalis-induced periodontitis, the alveolar bone resorption levels and periodontal pocket depth were significantly reduced after treatment with AE. AMCase protein expression was significantly higher in the disease group than in the healthy control (P<0.05). However, AE inhibited periodontal inflammation by downregulating AMCase expression in saliva and periodontal pocket tissue. AE significantly reduced RANKLstimulated osteoclastogenesis by modulating AMCase (P<0.05). Conclusions: AE decreases alveolar bone loss and periodontal inflammation, suggesting that this natural anthraquinone has potential value as a novel therapeutic agent against periodontal disease.
Abstract
Purpose: Aloe-emodin (AE), a natural anthraquinone abundant in aloe plants and rhubarb (Rheum rhabarbarum), has long been used to treat chronic inflammatory diseases. However, AE’s underlying mechanisms in periodontal inflammation have not been fully elucidated. Acidic mammalian chitinase (AMCase) is a potential biomarker involved in bone remodeling. This study aimed to evaluate AE’s effect on periodontitis in rats and investigate AMCase expression. Methods: Eighteen Sprague-Dawley rats were separated into the following groups: healthy (group 1), disease (group 2), vehicle (group 3), AE high-dose (group 4), and AE low-dose (group 5). Porphyromonas gingivalis ligatures were placed in rats (groups 2–5) for 7 days. Groups 4 and 5 were then treated with AE for an additional 14 days. Saliva was collected from all groups, and probing pocket depth was measured in succession. Periodontal pocket tissues were subjected to histomorphometric analysis after the rats were sacrificed. Bone marrowderived macrophages and murine macrophages were stimulated with receptor activator of nuclear factor-κB ligand (RANKL) and treated with different concentrations of AE. AMCase expression was detected from the analysis of saliva, periodontal pocket tissues, and differentiated osteoclasts. Results: Among rats with P. gingivalis-induced periodontitis, the alveolar bone resorption levels and periodontal pocket depth were significantly reduced after treatment with AE. AMCase protein expression was significantly higher in the disease group than in the healthy control (P<0.05). However, AE inhibited periodontal inflammation by downregulating AMCase expression in saliva and periodontal pocket tissue. AE significantly reduced RANKLstimulated osteoclastogenesis by modulating AMCase (P<0.05). Conclusions: AE decreases alveolar bone loss and periodontal inflammation, suggesting that this natural anthraquinone has potential value as a novel therapeutic agent against periodontal disease.
참고문헌 (36)
- Loos BG, "The role of inflammation and genetics in periodontal disease", Periodontol 2000, 83, pp.26~39 (2020)
- Haririan H, "Microbial analysis of subgingival plaque samples compared to that of whole saliva in patients with periodontitis", J Periodontol, 85, pp.819~828 (2014)
- Armingohar Z, "Polymorphisms in the interleukin-1gene locus and chronic periodontitis in patients with atherosclerotic and aortic aneurysmal vascular diseases", Scand J Immunol, 79, pp.338~345 (2014)
- Belibasakis GN, "Porphyromonas gingivalis induces RANKL in T-cells", Inflammation, 34, pp.133~138 (2011)
- Ono T, "RANKL biology: bone metabolism, the immune system, and beyond", Inflamm Regen, 40, pp.2~ (2020)
- Yang M, "Effects of omega-3 fatty acids and aspirin on Porphyromonas gingivalis-induced periodontitis in rats", J Periodontol, 90, pp.1307~1319 (2019)
- Dong X, "Aloe-emodin: a review of its pharmacology, toxicity, and pharmacokinetics", Phytother Res, 34, pp.270~281 (2020)
- Huang PH, "Emodin and aloe-emodin suppress breast cancer cell proliferation through ER α inhibition", Evid Based Complement Alternat Med, 2013, pp.376123~ (2013)
- Ipshita S, "One percent alendronate and aloe vera gel local host modulating agents in chronic periodontitis patients with class II furcation defects : a randomized, controlled clinical trial", J Investig Clin Dent, 9, pp.e12334~ (2018)
- Pradeep AR, "Adjunctive local delivery of aloe vera gel in patients with type 2diabetes and chronic periodontitis: a randomized, controlled clinical trial", J Periodontol, 87, pp.268~274 (2016)
- Bueter CL, "Innate sensing of chitin and chitosan", PLoS Pathog, 9, pp.e1003080~ (2013)
- Koch BE, "Keeping track of the growing number of biological functions of chitin and its interaction partners in biomedical research", Glycobiology, 25, pp.469~482 (2015)
- Lee CG, "Role of chitin and chitinase", chitinase-like proteins in inflammation, tissue remodeling, and injury, 2011, pp.73, 479~501
- Boot RG, "Identification of a novel acidic mammalian chitinase distinct from chitotriosidase", J Biol Chem, 276, pp.6770~6778 (2001)
- Zhu Z, "Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation", Science, 304, pp.1678~1682 (2004)
- Reese TA, "Chitin induces accumulation in tissue of innate immune cells associated with allergy", Nature, 447, pp.92~96 (2007)
- Shen CR, "The correlation between chitin and acidic mammalian chitinase in animal models of allergic asthma", Int J Mol Sci, 16, pp.27371~27377 (2015)
- Van Steijn GJ, "Chitinase in whole and glandular human salivas and in whole saliva of patients with periodontal inflammation", Eur J Oral Sci, 107, pp.328~337 (1999)
- Verhulst MJ, "A rapid, non-invasive tool for periodontitis screening in a medical care setting", BMC Oral Health, 19, pp.87~ (2019)
- Park MY, "Evaluation of aloin and aloe-emodin as anti-inflammatory agents in aloe by using murine macrophages", Biosci Biotechnol Biochem, 73, pp.828~832 (2009)
- Di Rosa M, "Chitinases as biomarkers in bone studies" (2017), Springer
- Asagiri M, "The molecular understanding of osteoclast differentiation", Bone, 40, pp.251~264 (2007)
- Teitelbaum SL, "Bone resorption by osteoclasts", Science, 289, pp.1504~1508 (2000)
- Elisia I, "Comparison of RAW264.7, human whole blood and PBMC assays to screen for immunomodulators", J Immunol Methods, 452, pp.26~31 (2018)
- Choi HJ, "Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways. Eur J Pharmacol 2010;636:28-35", Eur J Pharmacol, 636, pp.28~35 (2010)
- Dawes C, "The functions of human saliva : a review sponsored by the World Workshop on Oral Medicine VI", Arch Oral Biol, 60, pp.863~874 (2015)
- Heo SM, "Genetic relationships between respiratory pathogens isolated from dental plaque and bronchoalveolar lavage fluid from patients in the intensive care unit undergoing mechanical ventilation", Clin Infect Dis, 47, pp.1562~1570 (2008)
- Genco RJ, "Common risk factors in the management of periodontal and associated systemic diseases : the dental setting and interprofessional collaboration", J Evid Based Dent Pract, 14(Suppl), pp.4~16 (2014)
- Giannobile WV, "Salivary diagnostics: oral health and beyond!", J Dent Res, 90, pp.1153~1154 (2011)
- Öztürk VO, "Evaluation of active matrix metalloproteinase-8 (aMMP-8) chair-side test as a diagnostic biomarker in the staging of periodontal diseases", Arch Oral Biol, 124, pp.104955~ (2021)
- Tonetti MS, "Staging and grading of periodontitis: Framework and proposal of a new classification and case definition", J Clin Periodontol, 45(Suppl 20), pp.S149~S161 (2018)
- Van Steijn GJ, "Effect of periodontal treatment on the activity of chitinase in whole saliva of periodontitis patients", J Periodontal Res, 37, pp.245~249 (2002)
- Bertoldi C, "Non-bacterial protein expression in periodontal pockets by proteome analysis", J Clin Periodontol, 40, pp.573~582 (2013)
- Andryianau G, "Benzoxazepine-derived selective, orally bioavailable inhibitor of human acidic mammalian chitinase", ACS Med Chem Lett, 11, pp.1228~1235 (2020)
- Koralewski R, "Discovery of OATD-01, a first-in-class chitinase inhibitor as potential new therapeutics for idiopathic pulmonary fibrosis", J Med Chem, 63, pp.15527~15540 (2020)
- Kim Woo Jin, "Recent Advances of Therapeutic Targets for the Treatment of Periodontal Disease", Biomolecules & Therapeutics, 29(3), pp.263~267 (2021), 한국응용약물학회[DOI]
