Daidzin inhibits RANKL-induced osteoclastogenesis in vitro and prevents LPS-induced bone loss in vivo.

Osteoclasts are multinuclear giant cells responsible for bone resorption in bone loss diseases, including rheumatoid arthritis, periodontitis, and the aseptic loosening of orthopedic implants. Because of injurious side effects with currently available drugs, it is necessary to continue research novel bone-protective therapies. Daidzin, a naturally occurring isoflavone found in leguminous plants, has numerous beneficial pharmacologic effects, including anti-cancer, anti-cholesterol, and anti-angiocardiopathy, promoting osteoblasts differentiation, and even anti-osteoporosis. However, the effect of daidzin on the regulation of osteoclast activity has not yet been investigated. In this study, our study showed that daidzin significantly inhibited receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclast differentiation of bone marrow macrophages and the hydroxyapatite-resorbing activity of mature osteoclasts by inhibiting RANKL-induced NF-kB signaling pathway. In addition, daidzin could inhibit the expression of osteoclast marker genes, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene fos (c-Fos), tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK). Consistent with in vitro results, daidzin inhibited lipopolysaccharide-induced bone loss by suppressing the osteoclast differentiation. Together our data demonstrated that daidzin inhibits RANKL-induced osteoclastogenesis through suppressing NF-ĸB signaling pathway and that daidzin is a promising agent in the treatment of osteolytic diseases.

Arctigenin inhibits RANKL-induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle-induced bone loss in vivo.

Wear particle-induced bone resorption leads to prosthesis loosening, which is a major complication associated with total joint arthroplasty. Although the exact mechanism remains unclear, wear particle-induced extensive osteoclastogenesis plays a critical role in this process. Thus, a potential treatment of prosthetic loosening is focused on suppressing extensive osteoclast formation and bone resorption, which prevents wear particle-induced osteolysis. Arctigenin isolated from Arctium lappa has numerous beneficial pharmacologic effects, including anti-inflammatory, antiviral, and anticancer activities. Here, we explored the potential impact of arctigenin on titanium (Ti) particle-induced osteolysis in vivo. Our data showed that arctigenin significantly suppressed Ti particle-induced osteolysis and prevented bone destruction compared with Ti group. In addition, the number of osteoclasts reduced after treatment with arctigenin in vivo, indicating osteoclastogenesis might be inhibited by arctigenin. Next, bone marrow-derived macrophages were used to examine osteoclast differentiation, bone resorption, and activation of osteoclast-related signaling pathways. The results showed that arctigenin inhibited RANKL-induced osteoclastogenesis without any cytotoxicity and suppressed osteoclastic marker genes expression and hydroxyapatite resorption activity in a dose-dependent manner. Additionally, arctigenin suppressed receptor activator of nuclear factor κΒ (NF-κB) ligand-induced NF-κB activation, concomitant with retarded IκBɑ degradation and inhibition of p65 nuclear translocation, leading to impaired osteoclastogenesis. Collectively, our results suggest that arctigenin is a promising candidate for the treatment of osteoclast-related osteolytic diseases caused by excessive osteoclast formation.

Picroside II Attenuates CCI-Induced Neuropathic Pain in Rats by Inhibiting Spinal Reactive Astrocyte-Mediated Neuroinflammation Through the NF-κB Pathway.

Reactive astrocyte-mediated neuroinflammatory responses in the spinal dorsal horn have been reported to play a pivotal role in pathological pain. Chronic constriction injury (CCI) enhances the activation of nuclear factor kappa B (NF-κB), which is involved in neuropathic pain (NP). Picroside II (PII), a major active component of Picrorhiza scrophulariiflora, has been investigated for its anti-oxidative, anti-inflammatory, and anti-apoptotic activities. Here, we explored the analgesic effects of PII on a model of CCI-induced NP and investigated the levels of the GFAP protein and the mRNA and protein levels of pro-inflammatory cytokines in the spinal cord, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). CCI significantly induced mechanical allodynia and thermal hyperalgesia. Intraperitoneal administration of PII remarkably reversed the CCI-induced mechanical allodynia and thermal hyperalgesia and reduced the mRNA and protein levels of IL-1ß, IL-6, and TNF-α in the spinal cord. Additionally, according to the in vitro data, the PII treatment inhibited LPS-induced increases in the mRNA and protein levels of IL-1ß, IL-6, and TNF-α and suppressed the NF-κB pathway by inhibiting the phosphorylation of NF-κB/p65 and the degradation of inhibitor of NF-κB (IκB) in astrocytes without toxicity to astrocytes. Overall, the analgesic effect of PII correlated with the inhibition of spinal reactive astrocyte-mediated neuroinflammation through the NF-κB pathway in rats with NP.