Protective Effect Of Asiatic Acid On Rats Knee Osteoarthritis And The Mechanism

Osteoarthritis(OA)is a degenerative joint disease that damages articular cartilage and subchondral bone,causing joint pain and functional limitations in patients.The pathological changes of osteoarthritis start from articular cartilage,activate the reconstruction of osteoclasts and subchondral bones,and gradually affect the entire joint structure.Anti-inflammatory drugs are the main means of clinical treatment of osteoarthritis,but currently the drugs used in clinical have limited effects or have large side effects.Therefore,finding the pathological process for osteoarthritis can effectively inhibit cartilage degradation at the same time.Drugs that inhibit osteoclasts differentiation and that promote osteogenic differentiation are critical for the pretreatment of the disease.Asiatic acid is a kind of ursane-type pentacyclic triterpenic acid,which is mainly derived from Centella asiatica,which has important biological and pharmacological activities such as anti-inflammatory,anti-tumor,anti-oxidation and anti-hypertensive.However,the effect of asiatic acid on osteoclasts,osteoblasts,and chondrocytes is still unclear,and the effect on osteoarthritis remain to further research.In this context,bone marrow-derived monocytes,chondrocytes are extracted,including mouse embryonic osteoblast precursor cells.Cell viability is assessed by CCK-8,and chondrocytes,osteoclast,osteoblasts induced culture in vitro,by staining,RT-PCR,western blot to detect.In vivo experiments were performed using an anterior cruciate ligament transection to establish an animal model of rat knee osteoarthritis,using Micro-CT and tissue section staining to detect.Through study of the role of asiatic acid in the formation of osteoclasts and osteoblasts in vitro,the role of IL-1β-induced inflammatory chondrocytes and the effect of osteoarthritis in vivo,the possible mechanism of action was explored.The results showed that asiatic acid inhibited the expression of RANKL-induced osteoclast differentiation markers and IL-1β-induced chondrocyte inflammatory markers,and promoted the expression of osteoblast differentiation markers,thereby inhibiting osteolysis and promoting osteogenesis.At the same time,inhibiting the inflammation of chondrocytes.The mechanism by which asiatic acid can act on osteoclasts may be through inhibiting the production of NF-κB and MAPK signals upstream,and in addition,down-regulating the NFATc1 and c-fos signaling pathways in osteoclast differentiation.Inhibition of NF-κB and MAPK signaling pathways mediates anti-inflammatory and inhibitory osteoclast effects of asiatic acid.In vivo,after treatment of rat osteoarthritis with asiatic acid,Micro-CT scan and tissue section staining showed that asiatic acid significantly inhibited osteoclastogenesis in osteoarthritis and had the effect of protecting subchondral bone loss.These findings suggest that asiatic acid may be a therapeutic drug for the pathological process of osteoarthritis and has great application prospects.