title: Oral and topical boswellic acid attenuates mouse osteoarthritis.
abstract: OBJECTIVE
  Boswellic acid is a plant-derived molecule with putative anti-inflammatory effects. This study was performed to determine whether oral or topical administration of boswellic acid can attenuate joint damage in a mouse model of osteoarthritis (OA).
  
  
  METHODS
  Levels of boswellic acid were measured in the blood and synovium of mice treated with oral or topical boswellic acid. OA was generated by surgical destabilization of the medial meniscus (DMM). Therapy with oral or topical boswellic acid was initiated one day after surgery and continued for 12 weeks, when knees were harvested and scored histologically for degree of cartilage loss, osteophyte formation, and synovitis. Microdissected OA synovium was stimulated with IL-1β or lipopolysaccharide (LPS) in the presence or absence of boswellic acid and cytokine production by quantitative polymerase chain reaction (PCR) or multiplex enzyme linked immunoabsorbant assay (ELISA).
  
  
  RESULTS
  Topical treatment resulted in synovial concentrations of boswellic acid 2-6-fold higher than that measured in plasma. Cartilage loss was significantly reduced in mice treated with oral or topical boswellic acid compared with vehicle control (P < 0.01 for both oral and topical therapies). Likewise, treatment with either oral boswellic acid or boswellic acid ointment reduced of synovitis (P = 0.006 and 0.025, respectively) and osteophyte formation (P = 0.009 and 0.030, respectively). In vitro, boswellic acid was able to inhibit IL-1β and TLR4 mediated induction of several inflammatory mediators from OA synovial explant tissue.
  
  
  CONCLUSIONS
  Significant synovial concentration and therapeutic efficacy can be achieved with topical boswellic acid treatment. These findings suggest that boswellic acid has potential as a disease-modifying agent in OA.
authors.affiliation: GRECC, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Qilu Hospital, Shandong University, China.
authors.forename: X
authors.initials: X
authors.lastname: Pan
authors.affiliation: GRECC, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Wong
authors.affiliation: GRECC, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Wagner
authors.affiliation: GRECC, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Lahey
authors.affiliation: GRECC, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: wrobins@stanford.edu.
authors.forename: W H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: GRECC, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: sokolove@stanford.edu.
authors.forename: J
authors.initials: J
authors.lastname: Sokolove
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000276:immunology; D014315:Triterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C587672:IL1B protein, mouse; D018836:Inflammation Mediators; D053583:Interleukin-1beta; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014315:Triterpenes; C054625:boswellic acid
keywords: Disease modifying anti-osteoarthritis drugs; Osteoarthritis; Topical therapy