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Biomed Pharmacother. 2016 Apr;79:231-40. doi: 10.1016/j.biopha.2016.02.010. Epub 2016 Mar 11.

Lupeol acetate ameliorates collagen-induced arthritis and osteoclastogenesis of mice through improvement of microenvironment.

Author information

1
Dept of Orthopedic Surgery, Changhua Christian Hospital, Changhua, Taiwan.
2
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
3
Department of Radiation Oncology, Chang-Gung Memorial Hospital, Taoyen, Taiwan.
4
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Department of Radiation Oncology, Hsinchu Branch, Mackay Memorial Hospital, Hsinchu, Taiwan.
5
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.

Abstract

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 0-80μM of LA, and assayed for TNF-α, IL-1β, 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-α and IL-1β, (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.

KEYWORDS:

Collagen-induced arthritis; Lupeol acetate; Macrophage; Osteoclastogenesis; RANKL

PMID:
27044833
DOI:
10.1016/j.biopha.2016.02.010
[Indexed for MEDLINE]

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