Ginkgolide B monotherapy reverses osteoporosis by regulating oxidative stress-mediated bone homeostasis

• Published in: Free radical biology & medicine Vol. 168; pp. 234 - 246
• Main Authors: Lee, Chien-Wei, Lin, Hui-Chu, Wang, Belle Yu-Hsuan, Wang, Amanda Yu-Fan, Shin, Rita Lih-Ying, Cheung, Stella Yee Lo, Lee, Oscar Kuang-Sheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.05.2021
• Subjects: Aging; Ginkgo biloba extract; Ginkgolide B; Glucocorticoids; Osteoporosis; ROS; MPD; Glucocorticoids; Ginkgo biloba extract; Mϕ; GBE; Ginkgolide B; DEP; OVX; Osteoporosis; OB; OC; ROS; Aging; BMD; GB; MSC
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2021.03.008

Osteoporosis is characterized by reductions in bone mass, which could be attributed to the dysregulation of bone homeostasis, such as the loss of balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Elevated levels of oxidative stress increase bone resorption by promoting osteoclastogenesis and inhibiting the osteogenesis. Ginkgolide B (GB), a small natural molecule from Ginkgo biloba, has been reported to possess pharmacological activities by regulating reactive oxygen species (ROS) in aging-related degenerative diseases. Herein, we assessed the therapeutic effects of GB on the bone phenotypes of mice with osteoporosis induced by (I) aging, (II) ovariectomy, and (III) glucocorticoids. In all three animal models, oral gavage of GB significantly improved bone mass consistent with the increase in the OPG-to-RANKL ratio. In the in vitro experiments, GB promoted osteogenesis in aged mesenchymal stem cells (MSCs) and repressed osteoclastogenesis in aged macrophages by reducing ROS. The serum protein profile in GB-treated aged mice revealed moderate rejuvenating effects; signaling pathways associated with ROS were also regulated. The anabolic and anti-catabolic effects of GB were illustrated by the reduction in ROS. Our results indicate that GB is effective in treating osteoporosis. The use of GB in patients with osteoporosis is worthy of further clinical investigation. [Display omitted] •Oral gavage of GB protects bone in aging, postmenopausal, iatrogenic osteoporotic conditions and steady-state conditions.•GB regulates bone homeostasis by upregulating ROS scavengers in aged mesenchymal stem cells.•GB prevents oxidative stress-induced osteoclastogenesis in aged macrophages.