Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis
BackgroundOsteoporosis (OP), as the prevalent systemic metabolic bone disease worldwide, progresses insidiously and slowly. The clinical discomfort and complications associated with OP impose a significant burden on patients. Therefore, finding more effective treatments for OP remains an urgent chal...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1466057/full |
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| author | Kai Tang Kai Tang Kai Tang Wei Deng Wei Deng Wei Deng Wei Deng Zhiying Huang Zhiying Huang Zhiying Huang Simin Chen Simin Chen Simin Chen Zilin Zhu Zilin Zhu Shukun Lin Shukun Lin Lubin Zhong Lubin Zhong Quanxin Zheng Quanxin Zheng Wenhua Zhao Wenhua Zhao Zhida Zhang Zhida Zhang Ling Mo Ling Mo Ling Mo |
| author_facet | Kai Tang Kai Tang Kai Tang Wei Deng Wei Deng Wei Deng Wei Deng Zhiying Huang Zhiying Huang Zhiying Huang Simin Chen Simin Chen Simin Chen Zilin Zhu Zilin Zhu Shukun Lin Shukun Lin Lubin Zhong Lubin Zhong Quanxin Zheng Quanxin Zheng Wenhua Zhao Wenhua Zhao Zhida Zhang Zhida Zhang Ling Mo Ling Mo Ling Mo |
| author_sort | Kai Tang |
| collection | DOAJ |
| description | BackgroundOsteoporosis (OP), as the prevalent systemic metabolic bone disease worldwide, progresses insidiously and slowly. The clinical discomfort and complications associated with OP impose a significant burden on patients. Therefore, finding more effective treatments for OP remains an urgent challenge.MethodWe first conducted in vitro experiments to determine whether Neoandrographolide (NEO) exhibits cytotoxic or proliferative effects on bone marrow macrophages (BMMs) and to explore the specific timeframe during which NEO exerts its inhibitory action on osteoclast (OC) differentiation. Through Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot analysis, we examined the relative expression levels of genes and proteins associated with OC differentiation like CTSK,c-Fos,MMP9,NFATc1, and verified the underlying mechanisms. Finally, we performed in vivo experiments to further investigate the inflammation.ResultsNEO exhibits no significant cytotoxic effects on BMMs at concentrations less than or equal to 30 μM while exerting inhibitory effects on OC differentiation during its early and middle stages. RT-PCR and Western blot results reveal that NEO suppresses the expression of genes and proteins including CTSK,c-Fos,MMP9,NFATc1. Western blot findings also indicate that NEO inhibits the phosphorylation of ERK, P38, JNK, and P65 but does not reverse the degradation of IκB-α. Additionally, NEO affects the phosphorylation of proteins in the PI3K/AKT, GSK3β, and PPARγ signaling pathways, demonstrating that NEO can inhibit OC formation through multiple pathways and targets. In vivo experiments further validated the in vitro findings by constructing an OP model, showing that NEO can mitigate bone loss induced by OC differentiation.ConclusionNEO has the potential to serve as a therapeutic agent for OP by targeting multiple sites and inhibiting the formation of mature OC through various signaling pathways. |
| format | Article |
| id | doaj-art-1a909c88051247038b39cecd1c13552e |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-1a909c88051247038b39cecd1c13552e2025-02-11T11:29:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-02-011610.3389/fphar.2025.14660571466057Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosisKai Tang0Kai Tang1Kai Tang2Wei Deng3Wei Deng4Wei Deng5Wei Deng6Zhiying Huang7Zhiying Huang8Zhiying Huang9Simin Chen10Simin Chen11Simin Chen12Zilin Zhu13Zilin Zhu14Shukun Lin15Shukun Lin16Lubin Zhong17Lubin Zhong18Quanxin Zheng19Quanxin Zheng20Wenhua Zhao21Wenhua Zhao22Zhida Zhang23Zhida Zhang24Ling Mo25Ling Mo26Ling Mo27Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaFirst Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaFirst Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Eighth School of Clinical Medicine of Guangzhou University of Chinese Medicine, Foshan, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaFirst Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Spine Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaGuangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Spine Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaGuangzhou Medical University, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, Guangdong, ChinaBackgroundOsteoporosis (OP), as the prevalent systemic metabolic bone disease worldwide, progresses insidiously and slowly. The clinical discomfort and complications associated with OP impose a significant burden on patients. Therefore, finding more effective treatments for OP remains an urgent challenge.MethodWe first conducted in vitro experiments to determine whether Neoandrographolide (NEO) exhibits cytotoxic or proliferative effects on bone marrow macrophages (BMMs) and to explore the specific timeframe during which NEO exerts its inhibitory action on osteoclast (OC) differentiation. Through Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot analysis, we examined the relative expression levels of genes and proteins associated with OC differentiation like CTSK,c-Fos,MMP9,NFATc1, and verified the underlying mechanisms. Finally, we performed in vivo experiments to further investigate the inflammation.ResultsNEO exhibits no significant cytotoxic effects on BMMs at concentrations less than or equal to 30 μM while exerting inhibitory effects on OC differentiation during its early and middle stages. RT-PCR and Western blot results reveal that NEO suppresses the expression of genes and proteins including CTSK,c-Fos,MMP9,NFATc1. Western blot findings also indicate that NEO inhibits the phosphorylation of ERK, P38, JNK, and P65 but does not reverse the degradation of IκB-α. Additionally, NEO affects the phosphorylation of proteins in the PI3K/AKT, GSK3β, and PPARγ signaling pathways, demonstrating that NEO can inhibit OC formation through multiple pathways and targets. In vivo experiments further validated the in vitro findings by constructing an OP model, showing that NEO can mitigate bone loss induced by OC differentiation.ConclusionNEO has the potential to serve as a therapeutic agent for OP by targeting multiple sites and inhibiting the formation of mature OC through various signaling pathways.https://www.frontiersin.org/articles/10.3389/fphar.2025.1466057/fullneoandrographolideosteoclastogenesisMAPKNF-κBPI3K/AKTPPARγ |
| spellingShingle | Kai Tang Kai Tang Kai Tang Wei Deng Wei Deng Wei Deng Wei Deng Zhiying Huang Zhiying Huang Zhiying Huang Simin Chen Simin Chen Simin Chen Zilin Zhu Zilin Zhu Shukun Lin Shukun Lin Lubin Zhong Lubin Zhong Quanxin Zheng Quanxin Zheng Wenhua Zhao Wenhua Zhao Zhida Zhang Zhida Zhang Ling Mo Ling Mo Ling Mo Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis Frontiers in Pharmacology neoandrographolide osteoclastogenesis MAPK NF-κB PI3K/AKT PPARγ |
| title | Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis |
| title_full | Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis |
| title_fullStr | Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis |
| title_full_unstemmed | Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis |
| title_short | Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis |
| title_sort | neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis |
| topic | neoandrographolide osteoclastogenesis MAPK NF-κB PI3K/AKT PPARγ |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1466057/full |
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