Abstract

Flavonoids, found in a wide variety of foods and plants, are considered to play an important role in the prevention and treatment of osteoporosis. Our previous studies demonstrated that Erythrina cortex extract (EC) rich in prenylated isoflavonoids exerted bone protective effects in ovariectomized (OVX) rats. The present study aimed to investigate the interactions of gut microbiota with the EC extract to explore the underlying mechanisms involved in its beneficial effects on bone. Sprague-Dawley female rats of 3-months-old were ovariectomized and treated with EC extract for 12 weeks. EC extract reversed ovariectomy-induced deterioration of bone mineral density and bone microarchitecture as well as downregulated cathepsin K (Ctsk) and upregulated runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) in the tibia of OVX rats. Its protective effects on bone were correlated with changes in microbial richness and the restorations of several genera. EC increased the serum circulating levels of acetate and propionate in OVX rats. We conclude that the bone protective effects of EC extract were associated with the changes in microbial compositions and serum short chain fatty acids (SCFAs) in OVX rats.

Highlights

  • Osteoporosis is a major health problem that affects 200 million people worldwide, and became more and more prevalent due to the increase in the aging population [1]

  • The results showed that serum calcium (S_Ca), body weight at 12 weeks (BW_12), uterus index (UI) and urine calcium (Ur_Ca) were significantly correlated with more than six genera, while bone mineral density (BMD), serum phosphorous (S_P), serum alkaline phosphatase (S_ALP) showed correlations with fewer than or equal to three genera in mature rats

  • The present study revealed that the bone anabolic effects of the prenylated isoflavonoidsrich extract (EC) from Erythrinae Cortex was directly correlated with the restorations of changes in several microbial genera induced by ovariectomy

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Summary

Introduction

Osteoporosis is a major health problem that affects 200 million people worldwide, and became more and more prevalent due to the increase in the aging population [1]. Pharmacologic agents for the treatment of osteoporosis include hormone therapy, bisphosphonates, selective estrogen-receptor modulators, calcitonin, recombinant human parathyroid hormone and monoclonal antibody to receptor activator of nuclear factor κB ligand (RANKL) [1,5,6]. These commercially available drugs are effective, most have some limitations and adverse effects that limit their long-term administration and adherence [7,8]. Numerous clinical trials and experimental studies using bone cells and ovariectomized (OVX) animal models have suggested that flavonoids [12,13,14], especially prenylated isoflavonoids [15,16], may serve as an alternative therapy for bone health [17]

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