Abstract
Erxian decoction (EXD), a traditional Chinese medicine formula, has been used for treatment of osteoporosis for many years. The purpose of this study was to investigate the pharmacological effect of EXD in preventing osteoblast apoptosis and the underlying mechanism of prevention. Putative targets of EXD were predicted by network pharmacology, and functional and pathway enrichment analyses were also performed. Evaluations of bone mineral density, serum estradiol level, trabecular area fraction, serum calcium levels, and tumor necrosis factor (TNF)-α levels in ovariectomized rats, as well as cell proliferation assays, apoptosis assays, and western blotting in MC3T3-E1 osteoblasts were performed for further experimental validation. Ninety-three active ingredients in the EXD formula and 259 potential targets were identified. Functional and pathway enrichment analyses indicated that EXD significantly influenced the PI3K-Akt signaling pathway. In vivo experiments indicated that EXD treatment attenuated bone loss and decreased TNF-α levels in rats with osteoporosis. In vitro experiments showed that EXD treatment increased cell viability markedly and decreased levels of caspase-3 and the rate of apoptosis. It also promoted phosphorylation of Akt, nuclear translocation of transcription factor NF-erythroid 2-related factor (Nrf2), and hemeoxygenase-1 (HO-1) expression in TNF-α-induced MC3T3-E1 cells. Our results suggest that EXD exerted profound anti-osteoporosis effects, at least partially by reducing production of TNF-α and attenuating osteoblast apoptosis via Akt/Nrf2/HO-1 signaling pathway.
Highlights
Osteoporosis is a skeletal disease characterized by imbalanced bone homeostasis, which leads to an increase in bone fragility and fracture risk (Liu et al, 2017)
We previously reported that some components of Erxian decoction (EXD), such as icariin, curculigoside, and berberine, displayed inhibitory effects on osteoclastic bone resorption and positive effects on osteoblast proliferation (Wang et al, 2017a; Wang et al, 2017b)
A total of 93 compounds present in EXD met the criteria for inclusion (OB ≥ 30% and DL index ≥ 0.18)
Summary
Osteoporosis is a skeletal disease characterized by imbalanced bone homeostasis, which leads to an increase in bone fragility and fracture risk (Liu et al, 2017). Development of osteoporosis is mainly due to the production of a large number of immune and hematopoietic factors in the bone microenvironment (Yu and Wang, 2016). These complex and interacting factors influence the formation and absorption of bone (Wei and Frenette, 2018). One of the most important factors in osteoporosis is tumor necrosis factor-alpha (TNF-α), which is the strongest bone resorption enhancer and inhibits bone formation (Zhou et al, 2017a; Zhou et al, 2017b). EXD has been used to treat osteoporosis for several decades (Wang et al, 2016). Potential effects of EXD on TNF-α production and TNF-αinduced bone loss have not been investigated
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