title: Genistein suppresses Prevotella intermedia lipopolysaccharide-induced inflammatory response in macrophages and attenuates alveolar bone loss in ligature-induced periodontitis.
abstract: OBJECTIVE
  Genistein is a major isoflavone subclass of flavonoids found in soybean and a potent tyrosine kinase inhibitor. The present study aimed to assess the effect of genistein on the production of proinflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen associated with different forms of periodontal disease, and to evaluate its possible influence on alveolar bone loss in ligature-induced periodontitis using micro-computed tomography (micro-CT) analysis as well.
  
  
  METHODS
  LPS was isolated from P. intermedia ATCC 25611 by using the standard hot phenol-water method. Culture supernatants were analyzed for nitric oxide (NO) and interleukin-6 (IL-6). Inducible NO synthase (iNOS) protein expression was evaluated by immunoblot analysis. Real-time PCR was carried out to measure iNOS and IL-6 mRNA expression. In addition, effect of genistein on alveolar bone loss was evaluated in a rat model of experimental periodontitis using micro-CT analysis.
  
  
  RESULTS
  Genistein significantly attenuated P. intermedia LPS-induced production of iNOS-derived NO and IL-6 with attendant decrease in their mRNA expression in RAW264.7 cells. In addition, when genistein was administered to rats, decreases in alveolar bone height and bone volume fraction induced by ligature placement were significantly inhibited. Genistein administration also prevented ligature-induced alterations in the microstructural parameters of trabecular bone, including trabecular thickness, trabecular separation, bone mineral density and structure model index.
  
  
  CONCLUSIONS
  While additional studies are required, we suggest that genistein could be utilized for the therapy of human periodontitis in the future.
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Seung Han
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Ha
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Republic of Korea.
authors.forename: So-Hui
authors.initials: SH
authors.lastname: Choe
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Republic of Korea.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Hyeon
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea; Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Jeom-Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, Republic of Korea.
authors.forename: In Soon
authors.initials: IS
authors.lastname: Choi
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea; Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Gyeongsangnam-do, Republic of Korea; Institute of Translational Dental Sciences, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea. Electronic address: sungjokim@pusan.ac.kr.
authors.forename: Sung-Jo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D019833:Genistein / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D015850:Interleukin-6 / Q000096:biosynthesis; D008026:Ligation; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010518:Periodontitis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018713:Prevotella intermedia / Q000737:chemistry; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000093242:Interleukin-6 Inhibitors
chemical_list: D019833:Genistein; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C496319:NOS2 protein, human
keywords: Experimental periodontitis; Genistein; Lipopolysaccharide; Micro-computed tomography; Prevotella intermedia; Proinflammatory mediators