Enhanced anti-fibrogenic effects of novel oridonin derivative CYD0692 in hepatic stellate cells

Molecular and Cellular Biochemistry
Fredrick J BohanonRavi S Radhakrishnan

Abstract

Oridonin, isolated from Rabdosia rubescens, has been proven to possess various anti-neoplastic and anti-inflammatory properties. Previously, we reported the anti-fibrogenic effects of oridonin for liver in vitro. In the present study, we investigated the effects of a newly designed analog CYD0692 in vitro. Cell viability was measured by Alamar Blue assay. Cell apoptosis was assessed by Cell Death ELISA and Yo-Pro-1 staining. Western blots were performed for cellular proteins. Flow cytometry was used to measure cell cycle regulation. CYD0692 significantly inhibited LX-2 cells proliferation in a dose- and time-dependent manner with an IC50 value of ~0.7 μM for 48 h, ~tenfold greater potency than oridonin. Similar results were observed in HSC-T6 cells. In contrast, on the human hepatocyte cell line C3A, only 12 % of the cell growth was inhibited with 5 μM of CYD0692 treatment for 48 h, while 30 % inhibited at 10 μM. After CYD0692 treatment on LX-2 cells, apoptosis and S-phase cell cycle arrest were induced; cleaved-PARP, p21, and p53 were activated while cyclin-B1 levels declined. In addition, α-smooth muscle actin, type I Collagen, and fibronectin (FN) were markedly down regulated. Transforming growth factor β1 (TGF β1) has been ...Continue Reading

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Citations

Feb 23, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jimin XuJia Zhou
Jan 6, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Qing-Kun ShenZhe-Shan Quan
Apr 21, 2017·Mini Reviews in Medicinal Chemistry·Weiyan ChengXiaojian Zhang
Aug 27, 2016·International Journal of Molecular Sciences·Dahong LiJinyi Xu
Jan 29, 2019·BioMed Research International·Claire B CumminsRavi S Radhakrishnan
Nov 23, 2018·The Journal of Surgical Research·Claire B CumminsRavi S Radhakrishnan

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