Abstract

Rhus chinensis Mill. fruits are a kind of widely distributed edible seasoning, which have been documented to possess a variety of biological activities. However, its inhibitory effect on osteoclast formation has not been determined. The objective of this study was to evaluate the effect of the fruits on osteoclast differentiation of RAW264.7 cells, induced by receptor activator of nuclear factor-κB ligand (RANKL) and to illuminate the potential mechanisms using network pharmacology and western blots. Results showed that the extract containing two organic acids and twelve phenolic substances could effectively inhibit osteoclast differentiation in RANKL-induced RAW264.7 cells. Network pharmacology examination and western blot investigation showed that the concentrate essentially decreased the expression levels of osteoclast-specific proteins, chiefly through nuclear factor kappa-B, protein kinase B, and mitogen-activated protein kinase signaling pathways, particularly protein kinase B α and mitogen-activated protein kinase 1 targets. Moreover, the extract likewise directly down regulated the expression of cellular oncogene Fos and nuclear factor of activated T-cells cytoplasmic 1 proteins. Citric acid, quercetin, myricetin-3-O-galactoside, and quercetin-3-O-rhamnoside were considered as the predominant bioactive ingredients. Results of this work may provide a scientific basis for the development and utilization of R. chinensis fruits as a natural edible material to prevent and/or alleviate osteoporosis-related diseases.

Highlights

  • Human bones are constantly modified, and the dynamic balance of osteoblasts and osteoclasts is an important factor to maintain human bone health [1]

  • The inhibition of osteoclast differentiation has been considered as a potential therapy for the treatment and/or prevention of OP with few side effects

  • When comparing the mass data of the ethanolic extract to the mass data obtained from the literature, phytochemical standards or mass bank, 14 substances were identified, two of which were organic acids and 12 were phenols

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Summary

Introduction

Human bones are constantly modified, and the dynamic balance of osteoblasts and osteoclasts is an important factor to maintain human bone health [1]. When this homeostasis becomes imbalanced, it can induce the growth of bone-solubilizing diseases, such as osteoporosis (OP) [2,3], osteosclerosis [4], etc. The main manifestations of OP are exacerbation of bone organization microarchitecture, reduction of bone density and an increase in susceptibility to fragile fractures [5]. With the development of medical technology and the standard of living, the average life expectancy of people is increasing which is accelerating the aging of society, resulting in a higher prevalence of OP [9]. The inhibition of osteoclast differentiation has been considered as a potential therapy for the treatment and/or prevention of OP with few side effects

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