Abstract
Baicalein has been shown to have chondroprotective potential in vitro. However, its effect on disease modification in osteoarthritis (OA) is largely unknown. The present study is aimed at determining whether baicalein could slow the progression of OA and inhibit OA-related inflammation in a rat model of destabilization of the medial meniscus (DMM) and the underlying mechanisms. The rats subjected to DMM surgery were treated with baicalein (0.8, 1.6, and 3.2 μg/L, 50 μL, once a week) by intra-articular injection for 6 weeks. Dexamethasone (0.4 mg/mL, 50 μL, once a week) was used as a positive control. Histologic grading of cartilage degeneration was performed using the Osteoarthritis Research Society International (OARSI) recommended grading system (on a scale of 0-6). The expression levels of molecules associated with cartilage homeostasis and inflammatory cytokines were analyzed; moreover, the NLRP3 inflammasome activation and cartilage oxidative stress-associated molecules were determined. Baicalein treatment reduced the OARSI score and slowed OA disease progression in a dose-dependent manner within a certain range. Compared with DMM rats, intra-articular injection of baicalein led to (1) reduced levels of inflammatory mediates such as IL-1β and TNF-α, (2) reduced immunochemical staining of MMP-13 and ADAMTS-5, (3) suppressed immunochemical staining loss of type II collagen, (4) reduced expression of cartilage degradation markers including CTX-II and COMP in urine, and (5) inhibited NLRP3 inflammasome activation rather than regulated expression of SOD, GSH, and MDA. In contrast to the administration of baicalein, dexamethasone injection showed similar effects to slow OA progression, while dexamethasone inhibited NLRP3 inflammasome partly through decreasing levels of SOD, GSH, and MDA. This study indicated that baicalein may have the potential for OA prevention and exerts anti-inflammatory effects partly via suppressing NLRP3 inflammasome activation without affecting oxidative stress-associated molecules, and inhibition of cartilage catabolism enzymes in an OA rat model.
Highlights
Osteoarthritis (OA) is the most common arthritis and degenerative disease of the articular joints involving the articular cartilage, subchondral bone, and synovium and characterized by joint dysfunction, chronic pain, and disability [1]
Baicalein has been shown to alleviate the inflammatory process by reducing the expression of inflammatory cytokines such as IL-6, IL8, and iNOS, in contrast increasing IL-10 production [13] and inhibiting degrading enzymes of the extracellular matrix such as matrix metalloproteinase-3 (MMP-3) and MMP-13 in human chondrocytes and in IL-1β- and TNF-α-treated mouse articular cartilage explants [14]
The DMMinduced OA model was considered easier to operate than the anterior cruciate ligament (ACL) transection used in our previous study [5]
Summary
Osteoarthritis (OA) is the most common arthritis and degenerative disease of the articular joints involving the articular cartilage, subchondral bone, and synovium and characterized by joint dysfunction, chronic pain, and disability [1]. A variety of plant extracts, such as curcumin [4], L-theanine [5], and resveratrol [6], have been found to exert therapeutic or preventive effects on OA progression. Evidence from several studies suggested that baicalein is effective in mitigating OA chondrocyte apoptosis and inflammation in vitro. Baicalein has been shown to alleviate the inflammatory process by reducing the expression of inflammatory cytokines such as IL-6, IL8, and iNOS, in contrast increasing IL-10 production [13] and inhibiting degrading enzymes of the extracellular matrix such as matrix metalloproteinase-3 (MMP-3) and MMP-13 in human chondrocytes and in IL-1β- and TNF-α-treated mouse articular cartilage explants [14]. Our recent in vitro study determined the effects of baicalein on IL-1βinduced primary chondrocytes of rats. Baicalein treatment significantly inhibited NF-κB signaling pathway activation and suppressed apoptosis and matrix degradation, indicating that baicalein might exert OA protective effect [15]
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