RESUMO
BACKGROUND: Osteoporosis(OP) is a bone disease under research. Iron overload is a significant risk factor. Iron balance is crucial for bone metabolism and biochemical processes. When there is an excess of iron in the body, it tends to produce reactive oxygen species (ROS) which can cause oxidative damage to cells. The flavonoid compound, Cardamonin (CAR), possesses potent anti-inflammatory and anti-iron overload properties that can be beneficial in mitigating the risk of OP. PURPOSE: This study investigates the potential therapeutic interventions and underlying mechanisms of CAR for treating OP in individuals with iron overload. METHODS: The model of iron-overloaded mice was established by intraperitoneally injecting iron dextran(ID) into the mice. OP severity was evaluated with micro-CT and Hematoxylin-Eosin (HE) staining in vivo. In vitro, the iron-overloaded osteoblast model was induced by ferric ammonium citrate. Cell counting kit 8 assay to evaluate cell viability, Annexin V-FITC/PI assay to detect cell apoptosis. A range of cellular markers were detected, including the variation in mitochondrial membrane potential (MMP), levels of malondialdehyde (MDA), ROS, and lipid hydroperoxide (LPO). RESULTS: CAR can reverse bone loss in iron overload-induced OP mouse models in vivo. CAR attenuates the impairment of iron overload on the activity and apoptosis of MC3T3-E1 cells as well as the accumulation of ROS and LPO activation via HIF-1α/ROS pathways. CONCLUSION: CAR downregulating HIF-1α pathways prevents inhibition of iron overload-induced osteoblasts dysfunctional by attenuating ROS accumulation, reducing oxidative stress, promotes bone formation, and alleviates OP.
RESUMO
Knee Osteoarthritis (KOA) is an age-related progressive degenerative joint disease, which is featured with pain, joint deformity, and disability. Accumulating evidence indicated oxidative stress plays a crucial role in the occurrence and development of KOA. Curcumin is a polyphenolic compound with significant antioxidant activity among various diseases while catalase (CAT) is an enzyme degrading hydrogen peroxide in treating oxidative diseases. We previously showed that the expression of CAT was low in cartilage. However, the combination of curcumin and CAT in KOA is still elusive. In this study, we demonstrated that the combination of curcumin and CAT has the potential to inhibit the IL1ß-induced chondrocyte apoptosis without cytotoxicity in vitro. Mechanistically, we found that the synergistic application curcumin and CAT not only promotes curcumin's regulation of the NRF2/HO-1 signaling pathway to enhance antioxidant enzyme expression to remove superoxide radicals, but also CAT can further remove downstream hydrogen peroxide which enhances the ability to scavenge reactive oxygen species (ROS). In vivo, studies revealed that combination of curcumin and catalase could better inhibit oxidative stress-induced chondrocyte injury by promoting the expression of ROS scavenging enzymes. In sum, the combination of curcumin and catalase can be used to treat KOA. Thus, combination of curcumin and catalase may act as a novel therapeutic agent to manage KOA and our research gives a rationale for their combined use in the therapeutic of KOA.