Bone destruction or osteolysis marked by excessive osteoclastic bone resorption is a very common medical condition. Identification of agents that can effectively suppress excessive osteoclast formation and function is crucial for prevention and treatment of osteolytic conditions such as periprosthetic joint infection and periprosthetic loosening. Luteoloside, a flavonoid, is a natural bioactive compound with anti-inflammation and anti-tumor properties. However, the effect of Luteoloside on inflammation-induced osteolysis is unknown. Here, we found that Luteoloside exhibited a strong inhibitory effect on lipopolysaccharide (LPS)-induced osteolysis in vivo. In addition, Luteoloside suppressed RANKL-induced osteoclast differentiation and abrogated bone resorption in a dose-dependent manner. Further, we found that the anti-osteoclastic and anti-resorptive actions of Luteoloside are mediated via blocking NFATc1 activity and the attenuation of RANKL-mediated Ca signaling as well as NF-κB and MAPK pathways. Taken together, this study shows that Luteoloside may be a potential therapeutic agent for osteolytic bone diseases associated with abnormal osteoclast formation and function in inflammatory conditions.
Spinal cord injury (SCI) is a public health problem in the world. The SCI usually triggers an excessive inflammatory response that brings about a secondary tissue wreck leading to further cellular and organ dysfunction. Hence, there is great potential of reducing inflammation for therapeutic strategies of SCI. In this study, we aim to investigate if Salidroside (SAD) exerts an anti‐inflammatory effect and promotes recovery of motor function on SCI through suppressing nuclear factor‐κB (NF‐κB) and the mitogen‐activated protein kinase (MAPK) pathways. In vitro, real‐time polymerase chain reaction (PCR) and enzyme‐linked immunosorbent assay (ELISA) were used to examine the inhibitory effect of SAD on the expression and release of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) activated by lipopolysaccharide (LPS) in astrocytes. In addition, SAD was found to inhibit NF‐κB, p38 and extracellular‐regulated protein kinases (ERK) signaling pathways by western blot analysis. Further, in vivo study showed that SAD was able to improve hind limb motor function and reduce tissue damage accompanied by the suppressed expression of inflammatory cytokines IL‐1β, IL‐6, and TNF‐α. Overall, SAD could reduce the inflammatory response and promote motor function recovery in rats after SCI by inhibiting NF‐κB, p38, and ERK signaling pathways.
The increased activation of osteoclasts is the major manifestation of several lytic bone diseases, including osteoporosis, rheumatoid arthritis, aseptic loosening of orthopedic implants, Paget disease and malignant bone diseases. One important bone‐protective therapy in these diseases focuses on the inhibition of osteoclast differentiation and resorptive function. Given that the deleterious side‐effects of currently available drugs, it is beneficial to search for effective and safe medications from natural compounds. Cepharanthine (CEP) is a compound extracted from Stephania japonica and has been found to have antioxidant and anti‐inflammatory effects. In this study, we found that CEP inhibited receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast formation and bone‐resorbing activities using osteoclastogenesis and bone resorption assay. By polymerase chain reaction, we also found that CEP inhibited the expression of osteoclast‐differentiation marker genes including Ctsk, Calcr, Atp6v0d2, Mmp9 and Nfatc1. Mechanistic analyses including Western blot and luciferase reporter assay revealed that CEP inhibited RANKL‐induced activation of NF‐κB and nuclear factor of activated T‐cell, which are essential for the formation of osteoclast. Collectively, these data suggested that CEP can potentially be used as an alternative therapy for preventing or treating osteolytic diseases.
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