PMID- 27044833 OWN - NLM STAT- MEDLINE DCOM- 20161226 LR - 20161230 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 79 DP - 2016 Apr TI - Lupeol acetate ameliorates collagen-induced arthritis and osteoclastogenesis of mice through improvement of microenvironment. PG - 231-40 LID - S0753-3322(15)30336-X [pii] LID - 10.1016/j.biopha.2016.02.010 [doi] AB - Lupeol has been shown with anti-inflammation and antitumor capability, however, the poor bioavailability limiting its applications in living subjects. Lupeol acetate (LA), a derivative of lupeol, shows similar biological activities as lupeol but with better bioavailability. Here RAW 264.7 cells and bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS) were treated with 0-80muM of LA, and assayed for TNF-alpha, IL-1beta, COX-2, MCP-1 using Western blotting. Moreover, osteoclatogenesis was examined with reverse transcription PCR (RT-PCR) and tartrate-resistant acid phosphatase (TRAP) staining. For in vivo study, collagen-induced arthritis (CIA)-bearing DBA/1J mice were randomly separated into three groups: vehicle, LA-treated (50mg/kg) and curcumin-treated (100mg/kg). Therapeutic efficacies were assayed by the clinical score, expression levels of serum cytokines including TNF-alpha and IL-1beta, (18)F-fluorodeoxyglucose ((18)F-FDG) microPET/CT and histopathology. The results showed that LA could inhibit the activation, migration, and formation of osteoclastogenesis of macrophages in a dose-dependent manner. In RA-bearing mice, the expressions of inflammation-related cytokines were suppressed, and clinical symptoms and bone erosion were ameliorated by LA. The accumulation of (18)F-FDG in the joints of RA-bearing mice was also significantly decreased by LA. The results indicate that LA significantly improves the symptoms of RA by down-regulating expressions of inflammatory cytokines and osteoclastogenesis. CI - Copyright (c) 2016 Elsevier Masson SAS. All rights reserved. FAU - Wang, Wei-Hsun AU - Wang WH AD - Dept of Orthopedic Surgery, Changhua Christian Hospital, Changhua, Taiwan. FAU - Chuang, Hui-Yen AU - Chuang HY AD - Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. FAU - Chen, Chien-Hui AU - Chen CH AD - Department of Radiation Oncology, Chang-Gung Memorial Hospital, Taoyen, Taiwan. FAU - Chen, Wun-Ke AU - Chen WK AD - Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Department of Radiation Oncology, Hsinchu Branch, Mackay Memorial Hospital, Hsinchu, Taiwan. FAU - Hwang, Jeng-Jong AU - Hwang JJ AD - Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, Taiwan. Electronic address: jjhwang@ym.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160311 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (Pentacyclic Triterpenes) RN - 0 (RANK Ligand) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - O268W13H3O (lupeol) SB - IM MH - Animals MH - Arthritis, Experimental/*drug therapy/*pathology MH - Bone Marrow Cells MH - Cell Differentiation/drug effects MH - Cell Movement/drug effects MH - *Cellular Microenvironment/drug effects MH - Chemokine CCL2/metabolism MH - Cyclooxygenase 2/metabolism MH - Disease Models, Animal MH - Interleukin-1beta/metabolism MH - Lipopolysaccharides MH - Macrophages/metabolism MH - Mice MH - Osteoclasts/drug effects/*pathology MH - *Osteogenesis/drug effects MH - Pentacyclic Triterpenes/pharmacology/*therapeutic use MH - RANK Ligand/pharmacology MH - RAW 264.7 Cells MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Collagen-induced arthritis OT - Lupeol acetate OT - Macrophage OT - Osteoclastogenesis OT - RANKL EDAT- 2016/04/06 06:00 MHDA- 2016/12/27 06:00 CRDT- 2016/04/06 06:00 PHST- 2015/10/30 00:00 [received] PHST- 2016/02/23 00:00 [revised] PHST- 2016/02/23 00:00 [accepted] PHST- 2016/04/06 06:00 [entrez] PHST- 2016/04/06 06:00 [pubmed] PHST- 2016/12/27 06:00 [medline] AID - S0753-3322(15)30336-X [pii] AID - 10.1016/j.biopha.2016.02.010 [doi] PST - ppublish SO - Biomed Pharmacother. 2016 Apr;79:231-40. doi: 10.1016/j.biopha.2016.02.010. Epub 2016 Mar 11.