Osteoarthritis is a degenerative joint disease characterized by the progressive destruction of the cartilage extracellular matrix. In healthy cartilage, a low turnover of extracellular matrix molecules occurs. Proper balance of anabolic and catabolic activities is crucial for the maintenance of cartilage tissue and for the repair of molecular damages sustained during daily usage. In osteoarthritis (OA), this balance of anabolic and catabolic activities is compromised, tissue degradation predominates over the ability of tissue repair. Eventually this results in cartilage loss in persons with osteoarthritis. Catabolic activities in osteoarthritis (OA) are related to the increased release of cartilage degrading enzymes, while anabolic activities result in the production of type II collagen and aggrecan (a protein critical for cartilage structure and the function of joints). The cartilaginous matrix, which consists mainly of collagen and proteoglycans, is produced and maintained by chondrocytes (the only cells found in healthy cartilage).
It is known that high quantities of cytokines (small proteins that are released by cells and affect the behavior of other cells) such as IL-1b and TNF-a are produced in OA cartilage. IL-1b is a pro-inflammatory cytokine released by synoviocytes, chondrocytes, and invading macrophages in inflamed joints and has an important role in the development of OA. IL-1b triggers cartilage damage by the production of other pro-inflammatory cytokines, the production of catabolic enzymes and the release of inflammatory mediators. The up-regulation by IL-1b of these cytokines expression in chondrocytes is thought to be mediated by the activation of several transcription factors such as NF-kB, AP-1, and so on which are involved in stress- or inflammation-induced signaling.
The researchers investigated honokiol as a potential treatment for OA. Honokiol is a small-molecule purified from the bark of Magnolia officinalis, a plant used in traditional Chinese medicine without notable side effects for many years. It has been reported that honokiol for example down-regulates inflammatory responses. The researchers investigated in-vitro the effect of honokiol on the expression of various inflammatory factors and catabolic and anabolic factors in IL-1b-stimulated chondrocytes.
The data showed firstly that IL-1b markedly stimulated the expressions of iNOS and COX-2 and the productions of NO, PGE2, and IL-6 which are all part of a cascade of cartilage damage events. Secondly administration of honokiol significantly reversed this. Honokiol could also suppress the IL-1b-triggered activation of the IKK/IkBa/NF-kB signaling pathway. Moreover, honokiol significantly inhibited the IL-1b-induced MMP-13 enzyme production and collagen II reduction.
Taken together, this study suggests that honokiol may also have a chondroprotective effect in-vivo in humans and may be a potential therapeutic choice in the treatment of osteoarthritis patients.
The research report can be found here.