4‑Hexylresorcinol inhibits osteoclastogenesis by suppressing the NF‑κB signaling pathway and reverses bone loss in ovariectomized mice

Abstract

4-Hexylresorcinol (4HR) is a small organic compound that is widely used as an antiseptic and antioxidant. In the present study, its role in osteoclastogenesis was investigated. Bone marrow-derived macrophages from mice were used to examine the role of 4HR in osteogenesis. An ovariectomy (OVX) mouse model was constructed to examine the effect of 4HR in vivo, followed by hematoxylin and eosin and tartrate resistant acid phosphatase staining. In the present study, 4HR effectively suppressed receptor activator of NF-κB ligand-induced osteoclastogenesis in a dose-dependent manner. 4HR was also found to significantly suppress the expression of osteoclast (OC)-specific markers, including tartrate-resistant acid phosphatase, cathepsin K, nuclear factor of activated T-cell cytoplasmic 1 and c-Fos in the presence of RANKL in BMMs. Furthermore, 4HR inhibited osteoclastogenesis by inhibiting the activation of the NF-κB signaling pathway in BMMs. Consistent with the in vitro results, 4HR effectively ameliorated OVX-induced bone loss and markedly reduced OC number in the proximal tibia in vivo. In conclusion, the present results suggested that 4HR inhibited osteoclastogenesis in vitro and rescued bone loss in vivo, suggesting that 4HR may serve as a novel therapeutic agent for osteoporosis treatment.

4-Hexylresorcinol Inhibits Class I Histone Deacetylases in Human Umbilical Cord Endothelial Cells

“…However, 4HR might have more advantages for wound healing acceleration or treatment of metabolic disease than TSA. Recently, a Chinese team found that 4HR administration increases bone mineral density in the osteoporosis animal model [37].…”

4-Hexylresorcinol: pharmacologic chaperone and its application for wound healing

“…Thus, 4HR administration per os may be considered for the patients having osteoporosis. Recently, China team demonstrated 4HR administration per os has a therapeutic effect on osteoporosis in the animal model [ 73 ].…”

Therapeutic Potential of 4-Hexylresorcinol in Preserving Testicular Function in Streptozotocin-Induced Diabetic Rats

“…Given that both types of DM are characterized by chronic inflammation and disturbances in the immune system, inhibiting the nuclear factor kappa-light-chain-enhancer of the activated B cells (NF-κB) signaling pathway could mitigate some of the foundational processes of the disease. Since 4HR has been shown to inhibit NF-κB [24,25], its administration may offer a therapeutic strategy to alleviate the disturbances induced by DM. The administration of 4HR, through its roles in enhancing wound healing [22], exerting antioxidant effects [21], inhibiting the NF-κB pathway [24,25], and reducing serum glucose levels [23], may prove advantageous in mitigating complications in the testes induced by STZ-induced DM.…”

“…Since 4HR has been shown to inhibit NF-κB [24,25], its administration may offer a therapeutic strategy to alleviate the disturbances induced by DM. The administration of 4HR, through its roles in enhancing wound healing [22], exerting antioxidant effects [21], inhibiting the NF-κB pathway [24,25], and reducing serum glucose levels [23], may prove advantageous in mitigating complications in the testes induced by STZ-induced DM. While the administration of 4HR has been shown to lower serum testosterone levels and reduce mandibular size in growing healthy rats, indicating complex effects on testosterone dynamics [26], the implications of these findings for its therapeutic use, especially in diabetic testes, remain uncertain and warrant further investigation.…”