Arecanut (Areca catechu L.) seed polyphenol improves osteoporosis via gut-serotonin mediated Wnt/β-catenin pathway in ovariectomized rats

Abstract

Arecanut (Areca catechu L.) is one of the most important industrial crops in tropical Asia and parts of east Africa. However, the arecanut industry has suffered pandemic loss caused by negative reports such as carcinogenic effect. The healthy development of arecanut industry is of great significance. Our previous study found that arecanut (Areca catechu L.) seed polyphenol (ACP) can increase bone mass in ovariectomized rats which is closely related to metabolism of tryptophan. Here, we investigated the relationship among ACP, bone metabolism and serum metabolism in ovariectomized osteoporosis rat. We observed the bone structure of femur and analyzed the LDL-receptor relater protein 5 (LRP5), 5-hydroxytryptophan initial synthetase enzyme 1 (Tph1) and gut-derived serotonin (5-HT) in the gut, bone alkaline phosphatase (BALP), osteocalcin (OCN), Runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG) and receptor activator of nuclear factor NF-κB ligand (RANKL) in serum, 5-hydroxytryptophan receptor protein (Htr1b), bone morphogenetic protein-2 (BMP2) and β-catenin expression in bone and serum metabolites. The results indicated that compared with osteoporosis rats, ACP significantly improved the damaged bone structure, increased the ratio of OPG/RANKL, Lrp5, BMP2 and β-catenin. The ACP and E2 remarkably enhanced the expression of the metabolites such as 7-Ketodeoxycholic acid, indole and 15-Deoxy-Δ12, 14-prostaglandin, which were deeply linked with 5-HT synthesis via Lrp5 and tryptophan metabolism. Altogether, these studies shown that the ACP could downregulate 5-HT, which were implicated in serum metabolism and promoted bone mass by controlling the bone resorption and formation.