Abstract
We examined the antiosteoarthritic effect of the n-hexane extract of Litsea japonica fruit flesh (LJF-HE) in a rat model of monosodium-iodoacetate- (MIA-) induced osteoarthritis. LJF-HE significantly reduced the difference in weight-bearing capabilities of the hind paws between healthy and MIA-treated rats. Histological examination of the knee joints indicated that LJF-HE suppressed cartilage and bone destruction. Additionally, there were decreases in the expression of matrix metalloproteinase-2 and metalloproteinase-9 and cyclooxygenase-2 in the joints. The serum levels of deoxypyridinoline (DPD) and osteocalcin, which are markers of bone metabolism, also decreased. Furthermore, LJF-HE significantly suppressed infiltration of inflammatory cells into the synovium and inhibited the expression of proinflammatory cytokines such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1, and IL-6 in the joints and serum. The serum levels of leukotriene B4 and lipoxygenase were also significantly lowered by LJF-HE. Finally, LJF-HE inhibited the production of nitric oxide, prostaglandin E2, IL-6, and TNF-α in lipopolysaccharide-activated macrophages, which might be associated with inhibited phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Our data suggest that LJF-HE has an anti-inflammatory effect and may have potential as an antiosteoarthritic agent.
Highlights
Osteoarthritis (OA) is a degenerative joint disease in the aging population that can cause disability
During OA progression, activated osteoblasts induce the production of matrix metalloproteinases (MMPs) by chondrocytes, which leads to cartilage degradation [3]
We have previously reported that the ethanolic extract of this fruit has a significant antiosteoarthritic effect, which is exerted via suppression of cartilage degradation and subchondral bone deformation [10]
Summary
Osteoarthritis (OA) is a degenerative joint disease in the aging population that can cause disability. The functional limitation in the affected joint, which is caused by progressive degradation of cartilage and subchondral tissue remodeling, leads to bone deformity [1]. Subchondral bone osteoblasts produce proinflammatory cytokines such as interleukin- (IL-) 1, IL-6, and tumor necrosis factor-α (TNF-α). These trigger osteoclast activity, which leads to bone resorption [4] and an imbalance in bone metabolism. It has been reported that the fruit of this plant has antioxidant [6], anti-inflammatory [7], and antidiabetic effects [8]. We have previously reported that the ethanolic extract of this fruit has a significant antiosteoarthritic effect, which is exerted via suppression of cartilage degradation and subchondral bone deformation [10]. We evaluated the in vitro and in vivo antiosteoarthritic and anti-inflammatory effects of LJFHE
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