Novel RAS inhibitor 25-O-methylalisol F attenuates epithelial-to-mesenchymal transition and tubulo-interstitial fibrosis by selectively inhibiting TGF-β-mediated Smad3 phosphorylation

Chen, Hua; Yang, Tian; Wang, Minchang; Chen, Dan-Qian; Yang, Yang; Zhao, Ying-Yong

doi:10.1016/j.phymed.2018.03.034

Cited by 83 publications

(65 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…25-O-methylalisol F is a new tetracyclic triterpenoid compound isolated from the AR. Our study found that 25-O-methylalisol F suppressed EMT by inhibiting Smad3 phosphorylation and promoting Smad7 expression in TGF-β/ Smad-dependent pathway and it has an important effect on crosstalk between TGF-β/Smad and Wnt/β-catenin pathway in EMT process by activation of RAS [110].…”

Section: Targeting Tgf-β1/smad Signaling By Isolated Compoundsmentioning

confidence: 53%

New insights into TGF-β/Smad signaling in tissue fibrosis

Chen

Wang

et al. 2018

Chemico-Biological Interactions

Self Cite

737

480

View full text Add to dashboard Cite

Transforming growth factor-β1 (TGF-β1) is considered as a crucial mediator in tissue fibrosis and causes tissue scarring largely by activating its downstream small mother against decapentaplegic (Smad) signaling. Different TGF-β signalings play different roles in fibrogenesis. TGF-β1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-β1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-β1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-β1/Smad pathway thereby protects against TGF-β1-mediated fibrosis. This review presents an overview of the molecular mechanisms of TGF-β/Smad signaling pathway in renal, hepatic, pulmonary and cardiac fibrosis, followed by an in-depth discussion of their molecular mechanisms of intervention effects both in vitro and in vivo. The role of TGF-β/Smad signaling pathway in tumor or cancer is also discussed. Additionally, the current advances also highlight targeting TGF-β/Smad signaling pathway for the prevention of tissue fibrosis. The review reveals comprehensive pathophysiological mechanisms of tissue fibrosis. Particular challenges are presented and placed within the context of future applications against tissue fibrosis.

show abstract

Section: Targeting Tgf-β1/smad Signaling By Isolated Compoundsmentioning

confidence: 53%

New insights into TGF-β/Smad signaling in tissue fibrosis

Chen

Wang

et al. 2018

Chemico-Biological Interactions

Self Cite

737

480

View full text Add to dashboard Cite

show abstract

“…Juzep, exhibited diuretic, antihyperlipidemic, and renoprotective effects that were also confirmed by our previous studies . Our recent study demonstrated that triterpenoid was the main component of AR, and further study showed that the novel tetracyclic triterpenoid 25‐O‐methylalisol F inhibited EMT by suppressing the Wnt/β‐catenin signaling pathway as well as the phosphorylation of Smad3 signaling in both NRK‐52E and NRK‐49F cells (Figure and Table ). Additionally, it was also observed that ergone inhibited extracellular matrix accumulation in HK‐2 cells and attenuated podocyte injury through inhibiting the activation of the Wnt/β‐catenin signaling pathway induced by angiotensin II .…”

Section: Small Molecules Against Emtmentioning

confidence: 99%

“…Juzep, exhibited diuretic, antihyperlipidemic, and renoprotective effects 163 that were also confirmed by our previous studies. [164][165][166][167] Our recent study demonstrated that triterpenoid was the main component of AR, 30 and further study showed that the novel tetracyclic triterpenoid 25-O-methylalisol F inhibited EMT by suppressing the Wnt/β-catenin signaling pathway as well as the phosphorylation of Smad3 signaling in both NRK-52E and NRK-49F cells 30 (Figure 2 and Table 1).…”

Section: Wnt Signaling Pathwaymentioning

confidence: 99%

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Feng

Chen

Vaziri

et al. 2019

Medicinal Research Reviews

100

View full text Add to dashboard Cite

Tissue fibrosis and cancer both lead to high morbidity and mortality worldwide; thus, effective therapeutic strategies are urgently needed. Because drug resistance has been widely reported in fibrotic tissue and cancer, developing a strategy to discover novel targets for targeted drug intervention is necessary for the effective treatment of fibrosis and cancer. Although many factors lead to fibrosis and cancer, pathophysiological analysis has demonstrated that tissue fibrosis and cancer share a common process of epithelial‐mesenchymal transition (EMT). EMT is associated with many mediators, including transcription factors (Snail, zinc‐finger E‐box‐binding protein and signal transducer and activator of transcription 3), signaling pathways (transforming growth factor‐β1, RAC‐α serine/threonine‐protein kinase, Wnt, nuclear factor‐kappa B, peroxisome proliferator‐activated receptor, Notch, and RAS), RNA‐binding proteins (ESRP1 and ESRP2) and microRNAs. Therefore, drugs targeting EMT may be a promising therapy against both fibrosis and tumors. A large number of compounds that are synthesized or derived from natural products and their derivatives suppress the EMT by targeting these mediators in fibrosis and cancer. By targeting EMT, these compounds exhibited anticancer effects in multiple cancer types, and some of them also showed antifibrotic effects. Therefore, drugs targeting EMT not only have both antifibrotic and anticancer effects but also exert effective therapeutic effects on multiorgan fibrosis and cancer, which provides effective therapy against fibrosis and cancer. Taken together, the results highlighted in this review provide new concepts for discovering new antifibrotic and antitumor drugs.

show abstract

“…Natural products have been widely used for treatment of CKD in clinic (Zhao 2013;Tian et al 2014;Chen, Yang, et al 2018;Wang et al 2018;. Treatment with ergone (Zhao et al 2011(Zhao et al , 2012Zhao, Zhang, et al 2013), Rhubarb ) and the surface layer of Poria cocos (Zhao, Lei, et al 2013;Zhao, Li, et al 2013;Chen, Cao, et al 2019) could improve myriad diseases such as cancer, cardiovascular disease and kidney diseases.…”

Section: The Mechanism Of Ahr Ligands As Anticancer Drugsmentioning

confidence: 99%