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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Autores principales:	Jiaxiao Li, Zexin Chen, Hongbo Liao, Yanting Zhong, Junying Hua, Miaoling Su, Jiahao Li, Jinrong Xu, Liao Cui, Yang Cui
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ankylosing spondylitis Danshensu network pharmacology ossification fibroblast osteoblast Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/dbecbf7ce97c4156aec51fd3ca94ae1d
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spelling	oai:doaj.org-article:dbecbf7ce97c4156aec51fd3ca94ae1d2021-12-01T01:56:46ZAnti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology1663-981210.3389/fphar.2021.772190https://doaj.org/article/dbecbf7ce97c4156aec51fd3ca94ae1d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.772190/fullhttps://doaj.org/toc/1663-9812Ankylosing 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.Jiaxiao LiJiaxiao LiZexin ChenHongbo LiaoYanting ZhongJunying HuaMiaoling SuJiahao LiJinrong XuLiao CuiYang CuiYang CuiFrontiers Media S.A.articleankylosing spondylitisDanshensunetwork pharmacologyossificationfibroblastosteoblastTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ankylosing spondylitis Danshensu network pharmacology ossification fibroblast osteoblast Therapeutics. Pharmacology RM1-950
spellingShingle	ankylosing spondylitis Danshensu network pharmacology ossification fibroblast osteoblast Therapeutics. Pharmacology RM1-950 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
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.
format	article
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
title	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_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_sort	anti-osteogenic effect of danshensu in ankylosing spondylitis: an in vitro study based on integrated network pharmacology
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/dbecbf7ce97c4156aec51fd3ca94ae1d
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Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology

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