Comprehensive evaluation of the combined extracts of Epimedii Folium and Ligustri Lucidi Fructus for PMOP in ovariectomized rats based on MLP-ANN methods

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Drug evaluation; Icariin (PubChem CID: 5318997); Multi-layer perception; Oleanolic acid (PubChem CID: 10494); Postmenopausal osteoporosis; Rutin (PubChem CID: 5280805).