Abstract
Purpose: To investigate the fracture-healing effect of boeravinone B in ovariectomy-induced (OVX) osteoporotic rats.
 Methods: Adult female Wistar rats (n = 30) were ovariectomized and after three months, the unilateral cross-tibial fractures were fixed with intramedullary nails. The rats were then randomly assigned to three groups of 10 rats each: normal control group, OVX group and 100 mg/kg body weight boeravinone B group. Boeravinone B was orally administered for a period of 5 weeks. The effect of boeravinone B on indices of bone formation and resorption was assessed. Levels of inflammatory cytokines including tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the expression levels of NF-κB p65, IкB-α and SIRT1 proteins.
 Results: There were significant increases in the activities of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP), and collagen type I fragment (CTX) level and serum osteocalcin (OC) of OVX group, when compared with normal control group (p < 0.05). However, treatment with boeravinone B significantly reduced the activities and levels of these parameters, relative to OVX group (p < 0.05). The levels of TNF-α and IL-1β significantly increased in OVX group, relative normal control group, but were significantly lower following treatment with boeravinone B (p < 0.05). Bone mineral content (BMC) was not significantly altered in OVX and boeravinone B-treated groups, when compared with normal control group (p > 0.05). There was significant reduction in bone mineral density (BMD) of OVX group relative to normal control group (p < 0.05). However, treatment with boeravinone B significantly increased the BMD, when compared with OVX group (p < 0.05). After Week 5 of treatment, boeravinone B significantly enhanced bone remodeling and formation of callus. Treatment with boeravinone B significantly reduced the expression levels of NF-κB p65 and IκB-α proteins, and significantly upregulated the expression of SIRT-1 (p < 0.05).
 Conclusion: The results obtained in this study suggest that boeravinone B promotes the healing of fracture caused by osteoporosis via a mechanism involving NF-κB p65/IκB-α/SIRT-1 signaling pathway.
Highlights
Osteoporosis is a bone disorder characterized by loss of bone mass which leads to increased susceptibility to fractures and bone frailty due to disturbance in the micro-architecture of bone tissue [1]
Menopause is regulated by hormone replacement therapy (HRT), but HRT is limited by several factors and promotes ovarian, breast and endometrial cancers [5]
The present study investigated the fracture-healing effect of boeravinone B in ovariectomy-induced osteoporotic rats
Summary
Osteoporosis is a bone disorder characterized by loss of bone mass which leads to increased susceptibility to fractures and bone frailty due to disturbance in the micro-architecture of bone tissue [1]. Belongs to Nyctaginaceae family and grows in various parts of Asia, Africa and south America [7] It is traditionally used for the treatment of inflammation, stress, convulsion, dyspepsia and jaundice [8]. The present study investigated the fracture-healing effect of boeravinone B in ovariectomy-induced osteoporotic rats. The rats were housed in iron cages under optimum conditions: 12 h day/12 h night cycle, 24 °C and 60 - 65 % humidity. The blood was centrifuged at 3000 rpm for 10 min to obtain serum which was used for biochemical analysis. The X-ray analysis of rat tibia was performed after 3rd and 5th weeks of treatment to assess remodeling of bone and formation of callus. The resultant lysate was centrifuged at 12, 000 rpm for 10 min at 4 °C, and the protein concentration of the supernatant was determined using BCA assay kit. Groups were compared using Dunnett’s post hoc test, and values of p < 0.05 were considered statistically significant
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