Acacetin regulated the reciprocal differentiation of Th17 cells and Treg cells and mitigated the symptoms of collagen‐induced arthritis in mice

Liu, Lin; Yang, Jing; Zu, Beibei; Wang, Jingya; Sheng, Kang; Zhao, Lin; Xu, Weiwei

doi:10.1111/sji.12712

Cited by 29 publications

(16 citation statements)

References 26 publications

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“…Among these compounds, acacetin, helveticoside, lanatoside C, deferoxamine, famprofazone, tanespimycin and LY-294002 showed negative enrichment scores and thus may have the potential to perturb the development of JDM, while betonicine, felodipine, valproic acid, and sirolimus showed positive enrichment scores and might provide potentially therapeutic goals for JDM. Acacetin, an inhibitor of lipopolysaccharide-induced inflammation, can promote the expansion of Treg cells and supress the differentiation of Th17 cells in a dose-dependent manner in collagen-induced arthritis (Liu et al, 2018). Helveticoside can regulate metabolism and signaling processes as a biologically active component, but little is known in inflammatory reactions (Kim, Lee & Kim, 2015).…”

Section: Discussionmentioning

confidence: 99%

Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis

Zhong

Bai

et al. 2020

PeerJ

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Background. Juvenile dermatomyositis (JDM) is an immune-mediated disease characterized by chronic organ inflammation. The pathogenic mechanisms remain ill-defined. Methods. Raw microarray data of JDM were obtained from the gene expression omnibus (GEO) database. Based on the GSE3307 dataset with 39 samples, weighted correlation network analysis (WGCNA) was performed to identify key modules associated with pathological state. Functional enrichment analyses were conducted to identify potential mechanisms. Based on the criteria of high connectivity and module membership, candidate hub genes were selected. A protein-protein interaction network was constructed to identify hub genes. Another dataset (GSE11971) was used for the validation of real hub genes. Finally, the real hub genes were used to screen out smallmolecule compounds via the Connectivity map database. Results. Three modules were considered as key modules for the pathological state of JDM. Functional enrichment analysis indicated that responses to interferon and metabolism were dysregulated. A total of 45 candidate hub genes were selected according to the pre-established criteria, and 20 genes could differentiate JDM from normal controls by validation of another external dataset (GSE11971). These real hub genes suggested the pivotal role of mitochondrial dysfunction and interferon signature in JDM. Furthermore, drug repositioning highlighted the importance of acacetin, helveticoside, lanatoside C, deferoxamine, LY-294002, tanespimycin and L01AD from downregulated genes with the potential to perturb the development of JDM, while betonicine, felodipine, valproic acid, trichostatin A and sirolimus from upregulated genes provided potentially therapeutic goals for JDM. Conclusions. There are 20 real hub genes associated with the pathological state of JDM, suggesting the pivotal role of mitochondrial dysfunction and interferon signature in JDM. This analysis predicted several kinds of small-molecule compounds to treat JDM. Q. 2020. Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis. PeerJ 8:e8611 http://doi.Burrows FJ, Fritz LC, Feinstein DL. 2006. The heat-shock protein 90 inhibitor 17allylamino-17-demethoxygeldanamycin suppresses glial inflammatory responses and ameliorates experimental autoimmune encephalomyelitis. Journal of Neurochemistry Drinkard BE, Hicks J, Danoff J, Rider LG. 2003. Fitness as a determinant of the oxygen uptake/work rate slope in healthy children and children with inflammatory myopathy. Canadian Journal of Applied Physiology 28:888-897 DOI 10.1139/h03-063. Feldman BM, Rider LG, Reed AM, Pachman LM. 2008. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. . 2016. Vasculopathy-related clinical and pathological features are associated with severe juvenile dermatomyositis. Rheumatology 55:470-479 DOI 10.1093/rheumatology/kev359. Greenberg SA. 2010. Dermatomyositis and type 1 interferons. Current Rheumatology

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Section: Discussionmentioning

confidence: 99%

Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis

Zhong

Bai

et al. 2020

PeerJ

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“…Among these compounds, acacetin, helveticoside, lanatoside C, deferoxamine, famprofazone, tanespimycin and LY-294002 showed negative enrichment scores and thus may have the potential to perturb the development of JDM, while betonicine, felodipine, valproic acid, and sirolimus showed positive enrichment scores and might provide potentially therapeutic goals for JDM. Acacetin, an inhibitor of lipopolysaccharideinduced inflammation, can promote the expansion of Treg cells and supress the differentiation of Th17 cells in a dose-dependent manner in collagen-induced arthritis (Liu et al 2018). Helveticoside can regulate metabolism and signaling processes as a biologically active component, but little is known in inflammatory reactions (Kim et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis (v0.1)"

Golik¹

2020

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Background: Juvenile dermatomyositis (JDM) is an immune-mediated disease characterized by chronic organ inflammation. The pathogenic mechanisms remain illdefined; Methods: Raw microarray data of JDM were obtained from the gene expression omnibus (GEO) database. Based on GSE3307 dataset with 39 samples, weighted correlation network analysis (WGCNA) was performed to identify key modules associated with pathological state. Functional enrichment analyses were conducted to identify potential mechanisms. Based on the criteria of high connectivity and module membership, candidate hub genes were selected. A protein-protein interaction network was constructed to identify hub genes. Another dataset (GSE11971) was used for the validation of real hub genes. Finally, the real hub genes were used to screen out small-molecule compounds via the Connectivity map database ; Results: Three modules were considered as key modules for the pathological state of JDM. Functional enrichment analysis indicated that responses to interferon and metabolism were dysregulated. A total of 45 candidate hub genes were selected according to the pre-established criteria, and 20 genes could differentiate JDM from normal controls by validation of another external dataset (GSE11971). These real hub genes suggested the pivotal role of mitochondrial dysfunction and interferon signature in JDM. Furthermore, drug repositioning highlighted the importance of acacetin, helveticoside, lanatoside C, deferoxamine, LY-294002, tanespimycin and L01AD from downregulated genes with the potential to perturb the development of JDM, while betonicine, felodipine, valproic acid, trichostatin A and sirolimus from upregulated genes provided potentially therapeutic goals for JDM; Conclusions: There are 20 real hub genes associated with the pathological state of JDM, suggesting the pivotal role of mitochondrial dysfunction and interferon signature in JDM. This analysis predicted several kinds of smallmolecule compounds to treat JDM.

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“…More importantly, aloe-emodin has shown potential to treat hepatitis B viral infection [40], a condition that induces liver fibrosis, and to alleviate cardiac fibrosis via suppression of cardiac fibroblast activation by metastasis-associated protein 3 upregulation [41]. Functionally, acacetin has been reported to regulate the reciprocal differentiation of T helper 17 and regulatory T cells as well as the symptoms of collagen-induced arthritis in mice [42]. Additionally, it protects cardiomyocytes against hypoxia/reoxygenation injury by activating a series of intracellular signals involved in antioxidation, anti-inflammation, and antiapoptosis [43].…”

Section: Discussionmentioning

confidence: 99%

Development of A Novel Anti-Liver Fibrosis Formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis

Zhou

Cai

et al. 2020

Preprint

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Background: Liver fibrosis leads to loss of liver function. Xiaoyaosan decoction (XYS) as a classical Traditional Chinese Medicine (TCM) formula is used to treatment liver fibrosis in clinical and alleviated CCl4-induced liver fibrosis in our previous study.Xiaoyaosan decoction was composed of many ingredients, and the active ingredients is not clear. The Aim of this study is to explore the clarified compounds or compound combinations to treat liver fibrosis.Methods: Network pharmacology combined with transcriptomics analysis were used to analyze the Xiaoyaosan decoction (XYS) and liver depression and spleen deficiency syndrome liver fibrosis. This consisted constructed XYS-Syndrome-liver fibrosis network, the predict formula named LLAAF was develop from the network by topological analysis according to network stability. The anti-fibrosis effect was evaluated by in vitro and in vivo study.Results: According to the network XYS-Syndrome-liver fibrosis network, luteolin, licochalcone A, aloe-emodin, and acacetin formula (LLAAF) was predicted from 8 key compounds and 255 combinations in XYS, and LLAAF had a synergistic effect on the proliferation inhibition of hepatic stellate cells (HSCs) compared to each individual compound alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl4-induced liver fibrosis in rat. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signaling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signaling in vitro and in vivo.Conclusions: This study developed a novel anti-liver formula, LLAAF from XYS demonstrated the anti-liver fibrotic activity may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signaling.

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Acacetin regulated the reciprocal differentiation of Th17 cells and Treg cells and mitigated the symptoms of collagen‐induced arthritis in mice

Abstract: Our data demonstrated that acacetin mitigated the development of CIA and might be a potential agent for the treatment of autoimmune arthritis.

Cited by 29 publications

References 26 publications

Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis

Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis

Peer Review #2 of "Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis (v0.1)"

Development of A Novel Anti-Liver Fibrosis Formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis

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