Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology
Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by abnormal bone metabolism, with few effective treatments available. Danshensu [3-(3,4-dihydroxy-phenyl) lactic acid) is a bioactive compound from traditional Chinese medicine with a variety of pharmacologic effects. In the...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.772190/full |
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| author | Jiaxiao Li Jiaxiao Li Zexin Chen Hongbo Liao Yanting Zhong Junying Hua Miaoling Su Jiahao Li Jinrong Xu Liao Cui Yang Cui Yang Cui |
| author_facet | Jiaxiao Li Jiaxiao Li Zexin Chen Hongbo Liao Yanting Zhong Junying Hua Miaoling Su Jiahao Li Jinrong Xu Liao Cui Yang Cui Yang Cui |
| author_sort | Jiaxiao Li |
| collection | DOAJ |
| description | Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by abnormal bone metabolism, with few effective treatments available. Danshensu [3-(3,4-dihydroxy-phenyl) lactic acid) is a bioactive compound from traditional Chinese medicine with a variety of pharmacologic effects. In the present study, we investigated the pharmacologic effect and molecular mechanism of Danshensu in AS. Potential targets of Danshensu were identified in four drugs-genes databases; and potential pharmacologic target genes in AS were identified in three diseases-genes databases. Differentially expressed genes related to AS were obtained from the Gene Expression Omnibus database. Overlapping targets of Danshensu and AS were determined and a disease–active ingredient–target interaction network was constructed with Cytoscape software. Enrichment analyses of the common targets were performed using Bioconductor. To test the validity of the constructed network, an in vitro model was established by treating osteoblasts from newborn rats with low concentrations of tumor necrosis factor (TNF)-α. Then, the in vitro model and AS fibroblasts were treated with Danshensu (1–10 μM). Osteogenesis was evaluated by alkaline phosphatase staining and activity assay, alizarin red staining, quantitative PCR, and western blotting. We identified 2944 AS-related genes and 406 Danshensu targets, including 47 that were common to both datasets. The main signaling pathways associated with the targets were the c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. A low concentration of TNF-α (0.01 ng/ml) promoted the differentiation of osteoblasts; this was inhibited by Danshensu, which had the same effect on AS fibroblasts but had the opposite effect on normal osteoblasts. Danshensu also decreased the phosphorylation of JNK and ERK in AS fibroblasts. There results provide evidence that Danshensu exerts an anti-osteogenic effect via suppression of JNK and ERK signaling, highlighting its therapeutic potential for the treatment of AS. |
| first_indexed | 2024-12-19T04:37:31Z |
| format | Article |
| id | doaj.art-dbecbf7ce97c4156aec51fd3ca94ae1d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T04:37:31Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-dbecbf7ce97c4156aec51fd3ca94ae1d2022-12-21T20:35:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.772190772190Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network PharmacologyJiaxiao Li0Jiaxiao Li1Zexin Chen2Hongbo Liao3Yanting Zhong4Junying Hua5Miaoling Su6Jiahao Li7Jinrong Xu8Liao Cui9Yang Cui10Yang Cui11School of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Rheumatology and Immunology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Rheumatology and Immunology, South China Hospital of Shenzhen University, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Rheumatology and Immunology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaAnkylosing spondylitis (AS) is a chronic inflammatory disease characterized by abnormal bone metabolism, with few effective treatments available. Danshensu [3-(3,4-dihydroxy-phenyl) lactic acid) is a bioactive compound from traditional Chinese medicine with a variety of pharmacologic effects. In the present study, we investigated the pharmacologic effect and molecular mechanism of Danshensu in AS. Potential targets of Danshensu were identified in four drugs-genes databases; and potential pharmacologic target genes in AS were identified in three diseases-genes databases. Differentially expressed genes related to AS were obtained from the Gene Expression Omnibus database. Overlapping targets of Danshensu and AS were determined and a disease–active ingredient–target interaction network was constructed with Cytoscape software. Enrichment analyses of the common targets were performed using Bioconductor. To test the validity of the constructed network, an in vitro model was established by treating osteoblasts from newborn rats with low concentrations of tumor necrosis factor (TNF)-α. Then, the in vitro model and AS fibroblasts were treated with Danshensu (1–10 μM). Osteogenesis was evaluated by alkaline phosphatase staining and activity assay, alizarin red staining, quantitative PCR, and western blotting. We identified 2944 AS-related genes and 406 Danshensu targets, including 47 that were common to both datasets. The main signaling pathways associated with the targets were the c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. A low concentration of TNF-α (0.01 ng/ml) promoted the differentiation of osteoblasts; this was inhibited by Danshensu, which had the same effect on AS fibroblasts but had the opposite effect on normal osteoblasts. Danshensu also decreased the phosphorylation of JNK and ERK in AS fibroblasts. There results provide evidence that Danshensu exerts an anti-osteogenic effect via suppression of JNK and ERK signaling, highlighting its therapeutic potential for the treatment of AS.https://www.frontiersin.org/articles/10.3389/fphar.2021.772190/fullankylosing spondylitisDanshensunetwork pharmacologyossificationfibroblastosteoblast |
| spellingShingle | Jiaxiao Li Jiaxiao Li Zexin Chen Hongbo Liao Yanting Zhong Junying Hua Miaoling Su Jiahao Li Jinrong Xu Liao Cui Yang Cui Yang Cui Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology Frontiers in Pharmacology ankylosing spondylitis Danshensu network pharmacology ossification fibroblast osteoblast |
| title | Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology |
| title_full | Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology |
| title_fullStr | Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology |
| title_full_unstemmed | Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology |
| title_short | Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology |
| title_sort | anti osteogenic effect of danshensu in ankylosing spondylitis an in vitro study based on integrated network pharmacology |
| topic | ankylosing spondylitis Danshensu network pharmacology ossification fibroblast osteoblast |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.772190/full |
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