AUTHOR=Lin Ze , Xiong Yuan , Hu Yiqiang , Chen Lang , Panayi Adriana C. , Xue Hang , Zhou Wu , Yan Chenchen , Hu Liangcong , Xie Xudong , Sun Yun , Mi Bobin , Liu Guohui 

TITLE=Polydatin Ameliorates Osteoporosis via Suppression of the Mitogen-Activated Protein Kinase Signaling Pathway

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.730362

DOI=10.3389/fcell.2021.730362

ISSN=2296-634X

ABSTRACT=<p><bold>Purpose:</bold> Polydatin (POL) is a natural active compound found in <italic>Polygonum multiflorum</italic> with reported anti-oxidant and antiviral effects. With the aging population there has been a stark increase in the prevalence of osteoporosis (OP), rendering it an imposing public health issue. The potential effect of POL as a therapy for OP remains unclear. Therefore, we sought to investigate the therapeutic effect of POL in OP and to elucidate the underlying signaling mechanisms in its regulatory process.</p><p><bold>Methods:</bold> The POL-targeted genes interaction network was constructed using the Search Tool for Interacting Chemicals (STITCH) database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG). Pathways involved in OP and POL-targeted genes were identified. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the osteogenic genes and the phosphorylation level in pre-osteoblastic cells. In addition, ALP and alizarin red staining was used to test the effect of POL on extracellular matrix mineralization.</p><p><bold>Results:</bold> Twenty-seven KEGG pathways shared between POL-related genes and OP were identified. <italic>MAPK</italic> signaling was identified as a potential key mechanism. <italic>In vitro</italic> results highlighted a definitive anti-OP effect of POL. The phosphorylation levels of <italic>MAPK</italic> signaling, including <italic>p38</italic>α, <italic>ERK1/2</italic>, and <italic>JNK</italic>, were significantly decreased in this regulatory process.</p><p><bold>Conclusion:</bold> Our results suggest that POL has a promising therapeutic effect in OP. <italic>MAPK</italic> signaling may be the underlying mechanism in this effect, providing a novel sight in discovering new drugs for OP.</p>