Effects of the combined Herba Epimedii and Fructus Ligustri Lucidi on bone turnover and TGF-β1/Smads pathway in GIOP rats.
Kidney deficiency is the main pathogenesis of osteoporosis based on the theory of "kidney governing bones" in traditional Chinese medicine (TCM). Combined Herba Epimedii and Fructus Ligustri Lucidi, based on traditional Chinese formula Er-Zhi pills, were frequently used in TCM formulas that were prescribed for kidney tonifying and bone strengthening. However, it is unclear whether the combination of the two herbs may have a protective influence on glucocorticoid-induced osteoporosis (GIOP). The objective of this study was to evaluate the therapeutic effects and the underlying molecular mechanism of the decoction and the active fractions of the combined herbs in GIOP rats.
Male Sprague-Dawley rats were divided into seven groups, including the normal control (NC), GIOP model (MO), active fractions low (100mg/kg, LAF), active fractions high (200mg/kg, HAF), decoction low (3.5g/kg, LD), decoction high (7g/kg, HD) and Calcium with Vitamin D3 (0.2773g/kg, CaD)-treated group. The GIOP model was established by intramuscular injection of dexamethasone (1mg/kg) twice a week for 8 weeks. Different kinds of indicators were measured, including bone mineral density (BMD), bone biomechanical properties, serum bone alkaline phosphatase (b-ALP), serum bone γ-carboxyglutamic acid-containing protein (BGP), serum bone morphogenetic protein-2 (BMP-2), serum tartrate-resistant acid phosphatase (TRACP) and serum carboxy terminal cross linked telopeptide of typeⅠcollagen (ICTP), bone mineral content (BMC) and bone structured histomorphometry. The protein and mRNA expression of TGF-β1, Smad2, Smad3, Smad4 and Smad7 were detected by Western blotting (WB) and quantitative real time polymerase chain reaction (qRT-PCR), respectively.
Administration of combined Herba Epimedii and Fructus Ligustri Lucidi decoction and combined active fractions could significantly prevent GC-induced bone loss by increasing the contents of serum b-ALP, BGP and BMP-2 as the markers of bone formation, reducing the serum TRACP and ICTP contents to inhibit bone resorption and enhancing BMC. They could also attenuate biomechanical properties and BMD reduction, deterioration of trabecular architecture in MO rats. The mRNA and protein expressions of TGF-β1, smad2, smad3 and smad4 were up-regulated, and the mRNA and protein expression of Smad7 was down-regulated following combined Herba Epimedii and Fructus Ligustri Lucidi treatment.
Combination of Herba Epimedii and Fructus Ligustri Lucidi exhibited protective effects on promoting bone formation and precluding bone resorption. The underlying mechanism may be attributed to its regulations on TGF-β1/Smads pathway. The substance bases of the combined herbs on anti-osteoporosis were total flavonoids of Herba Epimedii, total iridoids and flavonoids of Fructus Ligustri Lucidi.
Yang Y
，Nian H
，Tang X
，Wang X
，Liu R
... -
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Comprehensive evaluation of the combined extracts of Epimedii Folium and Ligustri Lucidi Fructus for PMOP in ovariectomized rats based on MLP-ANN methods.
Kidney deficiency is the main pathogenesis of osteoporosis based on the theory of "kidney governing bones" in traditional Chinese medicine (TCM). Osteoporosis is a systemic disease; kidney deficiency influences the growth, aging and reproduction of human body, reflecting in endocrine, nerve, immunity, metabolism and other functions. Multi-target drugs composed of natural non-toxic products from kidney-reinforcing herbs, are being investigated for the treatment of osteoporosis. Therefore, it is necessary and imperative to develop an objective and comprehensive method to evaluate and compare the effects of herbs with listed drugs.
This study was designed to evaluate and compare the therapeutic effects and the underlying molecular mechanism of the combined extracts of Epimedii Folium and Ligustri Lucidi Fructus (EL) with Raloxifene hydrochloride (RH) in ovariectomy (OVX)-induced postmenopausal osteoporosis (PMOP) rats based on the multi-layer perception (MLP)-artificial neural network (ANN) model.
Female SD rats were subjected to either sham surgery (n = 8) or bilateral OVX (n = 48). One week after recovering from surgery, the OVX-induced rats were randomly divided into three groups: OVX model group (n = 32, every 8 rats were killed at the end of the 5th, 9th, 11th or 13th week after OVX), EL group (treated with EL 0.35 g/kg, n = 8), and RH group (treated with RH 6.25 mg/kg, n = 8). The rats in the treatment groups were administrated once a day for 12 weeks, then sacrificed. We observed bone mass and quality, bone remodeling, the function of estrogen and TGF-β1/Smads pathway in all rats.
Both EL and RH could increase bone mineral density, enhance bone strength, relieve bone micro-structure degeneration, re-balance bone remodeling, regulate estrogen dysfunction, and up-regulate TGF-β1 expression. The evaluation of the MLP-ANN model showed that EL and RH had markedly anti-PMOP effects, and there was no significant difference in the comprehensive evaluation of anti-osteoporosis between the two drugs. However, RH had better effects on bone mass and quality and TGF-β1/Smads pathway than EL; EL had better effects on estrogen function than RH.
Combined extracts of Epimedii Folium and Ligustri Lucidi Fructus (EL) exhibited bone-protective effects on PMOP. The MLP-ANN method evaluated the efficacy of drugs more comprehensively, which provided a new direction for the evaluation and comparison of drugs.
Ma Z
，Li X
，Chen Y
，Tang X
，Gao Y
，Wang H
，Liu R
... -
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