QingYan formula extracts protect against postmenopausal osteoporosis in ovariectomized rat model via active ER-dependent MEK/ERK and PI3K/Akt signal pathways

Abstract

Ethnopharmacological relevanceQingYan Formula has been traditionally used to tonify kidney and benefit essence, and QingYan Formula 70% ethanol extracts (QYFE) showed estrogen-like effect on reproductive system in our previous studies. However, there were no reports of QYFE on bone. Aim of the studyThis study offered preliminary insight of QYFE into the pharmacodynamics and mechanism of anti-bone osteoporosis in ovariectomized rats. Materials and methodsOVX rats were orally administrated QYFE or estradiol valerate (EV) for 12 weeks. We investigated the pharmacodynamic effects of QYFE on anti-bone loss in OVX rats, and also investigated the role of QYFE in promoting osteogenesis and inhibiting osteoclast differentiation. ResultsQYFE administration significantly reduced the degree of high bone turnover, dose-dependently repaired the damaged microstructure of trabecular and cortical bone by Hematoxylin-Eosin (HE) staining and micro-computed tomography (micro-CT), and reduced the number of femur osteoclasts by TRAP staining. QYFE enhanced the proliferation and activity of alkaline phosphatase (ALP), the phosphorylation levels of extracellular regulated kinase (ERK) and Akt in MG-63 cells, which was inhibited by ICI 182 780. Moreover, in RAW264.7 cells, QYFE inhibited osteoclasts differentiation, reduced the number of osteoclasts, decreased the activity of TRAP enzyme during formation, down-regulated the protein expression of p-ERK inhibited by ICI 182 780 and p-Akt not inhibited by ICI 182 780. ConclusionThis experiment demonstrated that QYFE had a definite anti-bone loss effect and had potential effect on postmenopausal osteoporosis. The molecular mechanism was related to the activation of estrogen receptor (ER)-dependent mitogen-activated protein kinase kinase (MEK)/ERK and phosphoinositide 3-kinase (PI3K)/Akt signal pathways in osteoblast, down-regulation protein expressions of ER-dependent p-ERK and ER-independent p-Akt in osteoclast.