Emodin alleviates cardiac fibrosis by suppressing activation of cardiac fibroblasts via upregulating metastasis associated protein 3

Xiao, Dan; Zhang, Yue; Wang, Rui; Fu, Yujie; Zhou, Tong; Diao, Hongtao; Wang, Zhixia; Yuan, Lin; Li, Zhange; Wen, Lin; Kang, Xujuan; Kopylov, F. Yu.; Shchekochikhin, Dmitri; Zhang, Yong; Yang, Baofeng

doi:10.1016/j.apsb.2019.04.003

Cited by 40 publications

(35 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, MTA3 also has anti-fibrosis effect (Qin et al, 2015). Xiao et al (2019) further demonstrated that the upregulation of MTA3 may be molecular mechanisms of emodin inhibiting cardiac fibrosis.…”

Section: Mta3mentioning

confidence: 91%

“…Emodin treatment in H9c2 cells with myocarditis Anti-apoptosis (Liu et al, 2013) caspase-3↓, Bcl-2↑ Emodin treatment in BALB/c mice and HEp-2 cells with viral myocarditis (Zhang et al, 2019) miR-138↑, MLK3↓, p53 and p21↓, cyclin D1↑, caspase-3 and caspase-9↓Sirt1/AKT, and Wnt/b-catenin pathways activated, Emodin treatment in H9c2 cells with myocardial ischemia (Huang et al, 2019) miR-26a↓, survivin↑, caspase-3, and caspase-9↓, JAK1/STAT3 signal activated Emodin treatment in H9c2 cells with myocardial ischemia (Ye et al, 2019) GSDMD-N↓, IL-1b↓, TLR4/MyD88/NF-kB/NLRP3 inhibited Emodin treatment in Sprague-Dawley rats cardiomyocytes with ischemia/reperfusion injury Anti-myocardial fibrosis (Xiao et al, 2019) MTA3↑, COL1A2, and a-SMA↓ Emodin treatment in mouse model of pathological cardiac hypertrophy with excess fibrosis Anti-cardiac hypertrophy (Evans et al, 2020) I HDAC and II HDAC activity inhibited, histone acetylation in cardiomyocytes↑, ERK phosphorylation inhibited Emodin treatment in C57BL/6 mice with cardiac hypertrophy (transverse aortic constriction-induced) and fibrosis (AngII-induced) (Gao et al, 2020) SIRT3↑, modulation of mitochondrial SIRT3 and its downstream signaling pathway…”

Section: References Finding Methodologymentioning

confidence: 99%

“…Emodin can improve multi-tissue fibrosis (Guan et al, 2016;Wang et al, 2016). Therefore, Xiao et al (2019) evaluated the beneficial effects and potential mechanisms of emodin on cardiac fibrosis. Firstly, it was observed that emodin can reduce cardiac fibrosis by TAC-induced and cardiac fibroblast activation by AngII-induced.…”

Section: Mta3mentioning

confidence: 99%

See 2 more Smart Citations

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Gao

Pang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Emodin is a natural occurring anthraquinone derivative isolated from roots and barks of numerous plants, molds, and lichens. It is found to be an active ingredient in different Chinese herbs including Rheum palmatum and Polygonam multiflorum, and it is a pleiotropic molecule with diuretic, vasorelaxant, anti-bacterial, anti-viral, antiulcerogenic, anti-inflammatory, and anti-cancer effects. Moreover, emodin has also been shown to have a wide activity of anti-cardiovascular diseases. It is mainly involved in multiple molecular targets such as inflammatory, anti-apoptosis, anti-hypertrophy, antifibrosis, anti-oxidative damage, abnormal, and excessive proliferation of smooth muscle cells in cardiovascular diseases. As a new type of cardiovascular disease treatment drug, emodin has broad application prospects. However, a large amount of evidences detailing the effect of emodin on many signaling pathways and cellular functions in cardiovascular disease, the overall understanding of its mechanisms of action remains elusive. In addition, by describing the evidence of the effects of emodin in detail, the toxicity and poor oral bioavailability of mice have been continuously discovered. This review aims to describe a timely overview of emodin related to the treatment of cardiovascular disease. The emphasis is to summarize the pharmacological effects of emodin as an anticardiovascular drug, as well as the targets and its potential mechanisms. Furthermore, the treatment of emodin compared with conventional cardiovascular drugs or target inhibitors, the toxicity, pharmacokinetics and derivatives of emodin were discussed.

show abstract

Section: Mta3mentioning

confidence: 91%

Section: References Finding Methodologymentioning

confidence: 99%

See 1 more Smart Citation

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Gao

Pang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…1D , the mRNA expression levels of the fibrotic markers, Col1α1, Col3α1, Ctgf and Fn , were notably upregulated in response to miR-375 inhibition. Increased expression levels of α-SMA and periostin in response to TGF-β are known to be hallmarks of myofibroblast transdifferentiation ( 41 ). Consistently, miR-375 inhibition was observed to exacerbate TGF-β-induced upregulation of α-SMA and periostin ( Fig.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‑375 prevents TGF‑β‑dependent transdifferentiation of lung fibroblasts via the MAP2K6/P38 pathway

et al. 2020

View full text Add to dashboard Cite

Transdifferentiation of lung fibroblasts to myofibroblasts is a crucial pathophysiological process in pulmonary fibrosis. MicroRNA-375 ( miR-375 ) was initially identified as a tumor-suppressive factor, and its expression was negatively associated with the severity of lung cancer; however, its role and potential mechanism in myofibroblast transdifferentiation and pulmonary fibrosis remain unclear. In the present study, human lung fibroblasts were stimulated with transforming growth factor-β (TGF-β) to induce myofibroblast transdifferentiation. A mimic and inhibitor of miR-375 , and their negative controls, were used to overexpress or suppress miR-375 in lung fibroblasts, respectively. The mRNA expression levels of fibrotic markers, and protein expression of α-smooth muscle actin and periostin, were subsequently detected by reverse transcription-quantitative PCR and western blotting, to assess myofibroblast transdifferentiation. miR-375 was markedly upregulated in human lung fibroblasts after TGF-β stimulation. The miR-375 mimic alleviated, whereas the miR-375 inhibitor aggravated TGF-β-dependent transdifferentiation of lung fibroblasts. Mechanistically, miR-375 prevented myofibroblast transdifferentiation and collagen synthesis by blocking the P38 mitogen-activated protein kinases (P38) pathway, and P38 suppression abrogated the deleterious effect of the miR-375 inhibitor on myofibroblast transdifferentiation. Furthermore, the present study revealed that mitogen-activated protein kinase kinase 6 was involved in P38 inactivation by miR-375 . In conclusion, miR-375 was implicated in modulating TGF-β-dependent transdifferentiation of lung fibroblasts, and targeting miR-375 expression may help to develop therapeutic approaches for treating pulmonary fibrosis.

show abstract

“…It also inhibits monolayer growth and anchorage-independent growth of androgen refractory prostate cancer PC3 cells by targeting the mTOR complex II [39]. 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].…”

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

View full text Add to dashboard Cite

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.

show abstract

Emodin alleviates cardiac fibrosis by suppressing activation of cardiac fibroblasts via upregulating metastasis associated protein 3

Cited by 40 publications

References 36 publications

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

MicroRNA‑375 prevents TGF‑β‑dependent transdifferentiation of lung fibroblasts via the MAP2K6/P38 pathway

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

Contact Info

Product

Resources

About