title: Brazilin isolated from Caesalpinia sappan L. inhibits rheumatoid arthritis activity in a type-II collagen induced arthritis mouse model.
abstract: BACKGROUND
  Caesalpinia sappan L. extracts exhibit great therapeutic potential, and have been shown to have analgesic and anti-inflammatory properties. This study aimed to understand the anti-rheumatoid activity of brazilin that was isolated from ethyl acetate extract of C. sappan L. The evaluations were conducted in mice with type-II collagen-induced arthritis (CIA).
  
  
  METHODS
  Brazilin was purified via preparative HPLC and identified by mass spectrometry and 1H/13C NMR analysis. DBA/1J mice were divided into four groups (n=10). Three groups of mice received intradermal injections of inducer bovine type-II collagen (BTIIC; 2 mg/ml in 0.05 ml acetic acid) and 0.1 ml of booster complete Freund's adjuvant (CFA). A second injection of BTIIC with booster incomplete Freund's adjuvant (ICFA) was given subsequently after 21 days. On 22nd day, purified brazilin (10 mg/kg body weight) or the disease-modifying anti-rheumatic drug methotrexate (3 mg/kg body weight) was administered intraperitoneally daily or every three days for 21 days, respectively to two groups of mice. At the 42nd day, mice sera were collected, and the levels of pro-inflammatory cytokines and stress enzyme markers in serum were measured using standard immunoassay methods. The microstructure and morphometric analyses of the bones were assessed using high-resolution microfocal computed tomography.
  
  
  RESULTS
  Brazilin isolated from C. sappan reduced the arthritis index score and the extent of acute inflammatory paw edema in CIA-mice. The bone mineral density was significantly (p<0.05) lower in only-CIA mice, and appeared to increase commensurate with methotrexate and brazilin administration. Brazilin prevented joint destruction, surface erosion, and enhanced bone formation as revealed by microstructural examinations. Brazilin markedly attenuated mouse CIA and reduced the serum levels of inflammatory cytokines including TNF-α, IL-1β, and IL-6.
  
  
  CONCLUSIONS
  Brazilin purified from C. sappan L. shows protective efficacy in CIA mouse, and may be useful to treat chronic inflammatory disorders including rheumatoid arthritis.
authors.affiliation: Department of Life Science and Biotechnology, Soonchunhyang University, Asan, Chungnam, 336-745, Republic of Korea. euigiljung@gmail.com.
authors.forename: Eui-Gil
authors.initials: EG
authors.lastname: Jung
authors.affiliation: Department of Life Science and Biotechnology, Soonchunhyang University, Asan, Chungnam, 336-745, Republic of Korea. n_han1017@hanmail.net.
authors.forename: Kook-Il
authors.initials: KI
authors.lastname: Han
authors.affiliation: Department of Life Science and Biotechnology, Soonchunhyang University, Asan, Chungnam, 336-745, Republic of Korea. coolsuny3@naver.com.
authors.forename: Seon Gu
authors.initials: SG
authors.lastname: Hwang
authors.affiliation: Department of Dental hygiene, Gimcheon University, 214 Daehakro, Gimcheon City Gyungbuk, 740-704, Korea. hjk621@hanmail.net.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Division of Plant Biotechnology, College of Agriculture and Life Science, Chonnam National University, Gwangju, 500-757, Republic of Korea. drbharatbhusan4@gmail.com.|School of Biotechnology, Trident Academy of Creative Technology (TACT), Bhubaneswar, 751007, Odisha, India. drbharatbhusan4@gmail.com.
authors.forename: Bharat Bhusan
authors.initials: BB
authors.lastname: Patnaik
authors.affiliation: Department of Life Science and Biotechnology, Soonchunhyang University, Asan, Chungnam, 336-745, Republic of Korea. kyh2098@nate.com.
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Life Science and Biotechnology, Soonchunhyang University, Asan, Chungnam, 336-745, Republic of Korea. mdhanpro61@gmail.com.
authors.forename: Man-Deuk
authors.initials: MD
authors.lastname: Han
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects; D029911:Caesalpinia / Q000737:chemistry*; D002417:Cattle; D024043:Collagen Type II; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids; D051379:Mice; D008811:Mice, Inbred DBA; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D001578:Benzopyrans; D024043:Collagen Type II; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D008055:Lipids; D010936:Plant Extracts; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant; C044362:brazilin