Silibinin Inhibits Proliferation and Migration of Human Hepatic Stellate LX-2 Cells

Abstract

Background: Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line. Methods: LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 mM). After 24 and 96 h of treatment, total cell number was determined by counting. Cytotoxicity was evaluated by trypan blue dye exclusion test. The expression profile of cMyc and peroxisome proliferator-activated receptor-g (PPAR-g) protein expressions was evaluated by Western blotting. Oxidative stress marker genes profile was quantified using qPCR. The migratory response of HSCs was observed by scrape wound healing assay. Results: SBN treatments significantly inhibit the LX-2 cell proliferation (without affecting its viability) in dose dependent manner. This treatment also retards the migration of LX-2 cells toward injured area. In Western blotting studies SBN treatment up regulated the protein expressions of PPAR-g and inhibited cMyc. Conclusion: The present study shows that SBN retards the proliferation, activation and migration of LX-2 cells without inducing cytotoxicity and oxidative stress. The profound effects could be due to cell cycle arresting potential of SBN. ( J CLIN EXP HEPATOL 2016;6:167-174)

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

“…Static HSCs are enriched for vitamin A. Once the liver stimulated by external factors, such as ethanol and Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake viruses, HSCs lose vitamin A and are activated (Ezhilarasan et al, 2016). Activated HSCs secret large amounts of liver fibrosis markers, including extracellular matrix (ECM) components such as collagen I, smooth muscle alpha-actin (α-SMA) and transforming growth factor-β (TGF-β).…”

Galewone, an Anti-Fibrotic Polyketide from Daldinia eschscholzii with an Undescribed Carbon Skeleton

“…The cell viability of CFSC-8B cells 14,15 was significantly inhibited by (−)-, (+)-, and (±)-galewone with the IC 50 values determined to be 3.73 ± 0.21, 10.10 ± 0.41, and 10.90 ± 0.62 μM, respectively (Table S1). Interestingly, (−)-galewone showed a much weaker cell viability inhibition effect on Lx-2 cells which in quiescent phase (LX-2 cells cultured 3 days as quiescent cells 1,16,17 ) with IC 50 value of 26.60 ± 3.87 μM than that in CFSC-8B cells (Fig. S1b and Table S1).…”

An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage

“…Our observation that silibinin did not promote the recovery process may also indicate that silibinin may not be involved in the regenerative mechanisms that restore normal hepatocyte function after DILI has occurred (Forbes and Newsome, 2016). However, silibinin has been shown to reduce stellate cell migration, which may reduce fibrotic activity (Ezhilarasan et al, 2016;Kim et al, 2012). Therefore, future directions to better characterise silibinin's hepatoprotection in the 2 5 case of recovery therapy may centre around the use of co-cultures, which can mimic paracrine responses.…”