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Abstract
BackgroundOsteoporosis is one of the world’s major medical burdens in the twenty-first century. Pharmaceutical intervention currently focusses on decelerating bone loss, but phytochemicals such as baicalein, which is a lipoxygenase inhibitor, may rescue bone loss. Studies evaluating the effect of baicalein in vivo are rare.MethodsWe administered baicalein to sixty-one three-month-old female Sprague-Dawley rats. They were divided into five groups, four of which were ovariectomized (OVX) and one non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, bilateral tibial osteotomy with plate osteosynthesis was performed and bone formation quantified. Baicalein was administered subcutaneously using three doses (C1: 1 mg/kg BW; C2: 10 mg/kg BW; and C3: 100 mg/kg BW) eight weeks after ovariectomy for four weeks. Finally, femora and tibiae were collected. Biomechanical tests, micro-CT, ashing, histological and gene expression analyses were performed.ResultsBiomechanical properties were unchanged in tibiae and reduced in femora. In tibiae, C1 treatment enhanced callus density and cortical width and decreased callus area. In the C3 group, callus formation was reduced during the first 3 weeks after osteotomy, correlating to a higher mRNA expression of Osteocalcin, Tartrate-resistant acid phosphatase and Rankl. In femora, baicalein treatments did not alter bone parameters.ConclusionsBaicalein enhanced callus density and cortical width but impaired early callus formation in tibiae. In femora, it diminished the biomechanical properties and calcium-to-phosphate ratio. Thus, it is not advisable to apply baicalein to treat early bone fractures. To determine the exact effects on bone healing, further studies in which baicalein treatments are started at different stages of healing are needed.
Highlights
Osteoporosis is one of the world’s major medical burdens in the twenty-first century
We showed that baicalein improved cortical bone in lumbar vertebrae, increased the bone formation rate by an enhancing serum alkaline phosphatase and had a favourable effect on skeletal muscle structure [19, 20]
We found that OVX delayed bone healing, whereas baicalein seemed to outweigh this OVX-induced effect partially because the occurrence of the osseous bridges was higher, especially in the C2 group, and the first bridging was seen earlier in baicalein-treated groups compared to the OVX group, but without leading to significant results due to the low number of tibiae analysed
Summary
Osteoporosis is one of the world’s major medical burdens in the twenty-first century. Further studies have revealed inhibition of the NF-κB signalling by baicalein. Through this pathway, baicalein (2019) 16:4 suppresses the function of TNFα, IL-6 and IL-1β, which are mediators of inflammation cascades [13]. The bone resorptive activity of osteoclasts was inhibited by baicalein by inhibiting osteoclast differentiation and promoting osteoclast apoptosis [17] In addition to these primary inflammation-based activities, baicalein was found to activate alkaline phosphatase by the mammalian target of rapamycin complex 1 (mTORC1) pathway and induce osteoblast differentiation markers and increase distinct bone parameters in the distal femur [18]
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