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Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways.

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资源类型：
Pubmed体系：
作者：
Hong Guoju[1,2,8] * ; Zhou Lin[2,3] * ; Han Xiaorui[4] ; Sun Ping[5] ; Chen Zhenqiu[1,6] ; He Wei[1,6] ; Tickner Jennifer[2] ; Chen Leilei[1,6] ; Shi Xuguang[7] ; Xu Jiake[2] ;
机构： [1]The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, China [2]School of Biomedical Sciences, the University of Western Australia, Perth, WA, Australia [3]Department of Endocrinology, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China [4]School of Medicine, South China University of Technology, Guangzhou, China [5]Department of Orthopedic, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China [6]Department of Orthopedic, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China [7]College of Chinese Materia Medical, Guangzhou University of Chinese Medicine, Guangzhou, China [8]Division of Orthopedic Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada
出处：
DOI： 10.3389/fphar.2020.00331
ISSN：

关键词： asiatic acid osteoclast RANKL bone resorption osteoporosis

摘要：
Asiatic acid is a triterpenoid compound extracted from a medicinal plant Centella asiatica. It has been used as a highly efficient compound for the treatment of cancer and hyperlipidemia, as well as possessing potential antiinflammatory properties. However, its effects on bone metabolism and osteoporosis haven't been reported. The purpose of our research were to reveal the biomolecular effects of asiatic acid on osteoclasts, and its underlying molecular mechanisms regulating its effects on receptor activator of NF-κB ligand (RANKL)-induced signaling pathways. We found that asiatic acid inhibited multinucleated tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast differentiation and osteoclast induced bone loss. Real time PCR showed that asiatic acid reduced the expression of down-cascade target genes including Ctsk, Nfatc1, Calcr, and Atp6v0d2. Western blot and luciferase reporter gene assays revealed that asiatic acid inhibits RANKL mediated NF-κB and NFATc1 signalings. Further, in vivo study demonstrated asiatic acid attenuates estrogen deficiency-induced bone loss in ovariectomized mice. MicroCT and histology analyses revealed that osteoclast numbers were significantly suppressed in asiatic acid treated groups. Furthermore, serum levels of TRAcP and CTX-1 were downregulated in treated groups. Taken together, our data show that asiatic acid can inhibit osteoclastic formation and reduce OVX-induced bone resorption through RANKL-activated NF-κB or NFATc1 signaling, suggesting that asiatic acid may be a potential and effective natural compound for the therapy of excessive RANKL-related osteolytic diseases. Copyright © 2020 Hong, Zhou, Han, Sun, Chen, He, Tickner, Chen, Shi and Xu.

基金：
Australian Health and Medical Research Council: APP1107828, APP1163933, APP1127156; National Natural Science Foundation of China: 81673999, 81704098; Guangdong Natural Science Funds for Distinguished Young Scholars: 2015A030306037; Science and Technology Planning Project of Guangdong Province: 2014A020221114. GH was a visiting scholar to UWA.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类 | 2 区 医学
小类 | 2 区 药学
最新[2025]版：
大类 | 3 区 医学
小类 | 3 区 药学
第一作者：
第一作者机构： [1]The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, China [2]School of Biomedical Sciences, the University of Western Australia, Perth, WA, Australia [8]Division of Orthopedic Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada
共同第一作者：
通讯作者：
通讯机构： [1]The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, China [6]Department of Orthopedic, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
推荐引用方式(GB/T 7714)：
Hong Guoju,Zhou Lin,Han Xiaorui,et al.Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways.[J].Frontiers in pharmacology.2020,11:331.doi:10.3389/fphar.2020.00331.
APA：
Hong Guoju,Zhou Lin,Han Xiaorui,Sun Ping,Chen Zhenqiu...&Xu Jiake.(2020).Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways..Frontiers in pharmacology,11,
MLA：
Hong Guoju,et al."Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways.".Frontiers in pharmacology 11.(2020):331

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