Biomed Pharmacother. 2022 Oct;154:113529.doi: 10.1016/j.biopha.2022.113529. Epub 2022 Aug 26. (IF7.419)

Praeruptorin B inhibits osteoclastogenesis by targeting GSTP1 and impacting on the S-glutathionylation of IKKβ

Kebin Xu  1 Ziyi Chen  2 Jialong Hou  2 Chenlin Dong  2 Chengge Shi  2 Linglin Gao  2 Zhixian Huang  2 Ge Shen  2 Te Wang  3 Yan Zhou  4

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Abstract

Osteoporosis a common disease in postmenopausal women which contains significant impact on the living quality of women. With the aging of the population, the number of patients suffer from osteoporosis has shown a significant increase. Given the limitations of clinical drugs for the treatment of osteoporosis, natural extracts with small side effects have a great application prospect in the treatment of osteoporosis. Praeruptorin B (Pra-B), is one of the main components found in the roots of Peucedanum praeruptorum Dunn and exhibits anti-inflammatory effects. However, there is no research on the influence of Pra-B on osteoporosis. Here, we showed that Pra-B can dose-dependently suppress osteoclastogenesis without cytotoxicity. Receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-induced the nuclear import of P65 was inhibited by Pra-B, which indicated the suppressive effect of Pra-B on NF-κB signaling. Further, Pra-B enhanced the expression of Glutathione S-transferase Pi 1 (GSTP1) and promoted the S-glutathionylation of IKKβ to inhibit the nuclear translocation of P65. Moreover, in vivo experiments showed that Pra-B considerably attenuated the bone loss in ovariectomy (OVX)-induced mice. Collectively, our studies revealed that Pra-B suppress the NF-κB signaling targeting GSTP1 to rescued RANKL-induced osteoclastogenesis in vitro and OVX-induced bone loss in vivo, supporting the potential of Pra-B for treating osteoporosis in the future.

Keywords: GSTP1; Nuclear factor κB; Osteoclastogenesis; Osteoporosis; Praeruptorin B; Receptor activator of nuclear factor κB ligand.

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