AUTHOR=Ju Linjie , Hu Peipei , Chen Ping , Wu Jiejie , Li Zhuoqun , Qiu Zhixia , Cheng Jun , Huang Fang 

TITLE=Corydalis Saxicola Bunting Total Alkaloids Attenuate Walker 256-Induced Bone Pain and Osteoclastogenesis by Suppressing RANKL-Induced NF-κB and c-Fos/NFATc1 Pathways in Rats

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.609119

DOI=10.3389/fphar.2020.609119

ISSN=1663-9812

ABSTRACT=<p>Metastatic bone pain is characterized by insufferable bone pain and abnormal bone structure. A major goal of bone cancer treatment is to ameliorate osteolytic lesion induced by tumor cells. <italic>Corydalis saxicola</italic> Bunting total alkaloids (CSBTA), the alkaloid compounds extracted from the root of <italic>C. saxicola</italic> Bunting, have been shown to possess anticancer and analgesic properties<italic>.</italic> In this study, we aimed to verify whether CSBTA could relieve cancer induced bone pain and inhibit osteoclastogenesis. The <italic>in vivo</italic> results showed that CSBTA ameliorated Walker 256 induced bone pain and osteoporosis in rats. Histopathological changes also supported that CSBTA inhibited Walker 256 cell-mediated osteolysis. Further <italic>in vitro</italic> analysis confirmed that CSBTA reduced the expression of RANKL and downregulate the level of RANKL/OPG ratio in breast cancer cells. Moreover, CSBTA could inhibit osteoclastogenesis by suppressing RANKL-induced NF-κB and c-Fos/NFATc1 pathways. Collectively, this study demonstrated that CSBTA could attenuate cancer induced bone pain via a novel mechanism. Therefore, CSBTA might be a promising candidate drug for metastatic bone pain patients.</p>