Morus bombycis Koidzumi extract suppresses collagen-induced arthritis by inhibiting the activation of nuclear factor-κB and activator protein-1 in mice.
BACKGROUND
Morus bombycis Koidzumi is widely distributed in Asia. In Korea, it has been used in traditional medicine because of its apparent anti-inflammatory, antioxidant, and hepatoprotective properties.


OBJECTIVE
Although the extract of Morus bombycis Koidzumi (MB) has long since been used as a traditional anti-inflammatory medicine in Korea, its effect on arthritis remains unknown. We aimed to investigate the anti-arthritis activity of MB and the mechanism underlying it.


METHODS
The anti-arthritis activity of MB was assessed by using mouse models of type II collagen-induced arthritis (CIA). The clinical arthritis index and histopathological changes were evaluated in mice. Reverse transcriptase-polymerase chain reaction (RT-PCR), electrophoretic mobility shift assay (EMSA), and other biologic approaches were used for measuring the effect of MB on arthritis and understanding the underlying mechanism.


RESULTS
MB significantly decreased the clinical arthritis index in CIA mice; this was confirmed by examining histological changes in joints. Infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw were largely suppressed by MB. The mRNA levels of matrix metalloproteinase (MMP)-1/MMP-3, inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6), and chemokines (macrophage inflammatory protein (MIP)-1, monocyte chemoattractant protein (MCP)-1, RANTES) were significantly suppressed by MB in a dose-dependent manner. The number of osteoclasts in the hind tibia was also significantly decreased. With regard to the mechanism, MB suppressed the activation of nuclear factor (NF)-κB and activator protein (AP)-1 in CIA mice.


CONCLUSIONS
MB produced an anti-arthritis effect in CIA mice by inhibiting the production of critical inflammatory mediators and osteoclasts through the downregulation of NF-κB and AP-1.
Department of Immunology and Physiology, College of Medicine, Konkuk University, Chungju, Republic of Korea.
Hyuk Soon
HS
Kim
A-Ram
AR
Kim
Hye Jin
HJ
Park
Dong Ki
DK
Park
Do Kyun
DK
Kim
Na Young
NY
Ko
Bokyung
B
Kim
Dong Kug
DK
Choi
Hyung Sik
HS
Won
Wha Sup
WS
Shin
Young Mi
YM
Kim
Wahn Soo
WS
Choi
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects; D002356:Cartilage / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia / Q000188:drug therapy; D007109:Immunity / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D031625:Morus; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018547:Plant Stems; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D018808:Transcription Factor AP-1