Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways
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 osteopo...
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00331/full |
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| author | Guoju Hong Guoju Hong Lin Zhou Lin Zhou Xiaorui Han Ping Sun Zhenqiu Chen Zhenqiu Chen Wei He Wei He Jennifer Tickner Leilei Chen Leilei Chen Xuguang Shi Jiake Xu |
| author_facet | Guoju Hong Guoju Hong Lin Zhou Lin Zhou Xiaorui Han Ping Sun Zhenqiu Chen Zhenqiu Chen Wei He Wei He Jennifer Tickner Leilei Chen Leilei Chen Xuguang Shi Jiake Xu |
| author_sort | Guoju Hong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T19:24:43Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T19:24:43Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e4438c948ee84e7db8be4886525d2b852022-12-21T23:34:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-03-011110.3389/fphar.2020.00331509532Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling PathwaysGuoju Hong0Guoju Hong1Lin Zhou2Lin Zhou3Xiaorui Han4Ping Sun5Zhenqiu Chen6Zhenqiu Chen7Wei He8Wei He9Jennifer Tickner10Leilei Chen11Leilei Chen12Xuguang Shi13Jiake Xu14The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Biomedical Sciences, the University of Western Australia, Perth, WA, AustraliaSchool of Biomedical Sciences, the University of Western Australia, Perth, WA, AustraliaDepartment of Endocrinology, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Orthopedic, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaThe National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Orthopedic, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Orthopedic, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Biomedical Sciences, the University of Western Australia, Perth, WA, AustraliaThe National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Orthopedic, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaCollege of Chinese Materia Medical, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Biomedical Sciences, the University of Western Australia, Perth, WA, AustraliaAsiatic 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.https://www.frontiersin.org/article/10.3389/fphar.2020.00331/fullasiatic acidosteoclastRANKLbone resorptionosteoporosis |
| spellingShingle | Guoju Hong Guoju Hong Lin Zhou Lin Zhou Xiaorui Han Ping Sun Zhenqiu Chen Zhenqiu Chen Wei He Wei He Jennifer Tickner Leilei Chen Leilei Chen Xuguang Shi Jiake Xu Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways Frontiers in Pharmacology asiatic acid osteoclast RANKL bone resorption osteoporosis |
| title | Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways |
| title_full | Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways |
| title_fullStr | Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways |
| title_full_unstemmed | Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways |
| title_short | Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways |
| title_sort | asiatic acid inhibits ovx induced osteoporosis and osteoclastogenesis via regulating rankl mediated nf κb and nfatc1 signaling pathways |
| topic | asiatic acid osteoclast RANKL bone resorption osteoporosis |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00331/full |
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