Effects of Armepavine Against Hepatic Fibrosis Induced by Thioacetamide in Rats

Abstract

The aim of this study was to investigate if armepavine (Arm, C₁₉H₂₃O₃N) could exert inhibitory effects against hepatic fibrosis in rats. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with tumour necrosis factor-α (TNF-α) to evaluate the inhibitory effects of Arm. Rats were injected with thioacetamide (TAA; 300 mg/kg, intraperitoneally) thrice a week for 4 weeks to induce hepatic fibrosis, with Arm (3 or 10 mg/kg) given by gavage twice a day. Liver sections were taken for western blotting, fibrosis scoring and immunofluorescence staining. Arm (1-10 µm) concentration-dependently attenuated TNF-α-stimulated: (i) protein expressions of α-smooth muscle actin (α-SMA), collagen type I and angiopoietin-1; (ii) H₂O₂ production; and (iii) NF-κB, JunD and C/EBPß (cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding protein-ß (EBPß)) nuclear translocations in HSC-T6 cells. In vivo Arm treatment significantly reduced plasma aspartate transaminase and alanine transaminase levels, hepatic α-SMA expression and collagen contents, and fibrosis scores of TAA-injected rats. Moreover, Arm treatment decreased α-SMA- and NF-κB-positive cells in immunohistochemical staining, and mRNA expression levels of IL-6, TGF-ß1, TIMP-1, col1α2, iNOS and ICAM-1 genes, but up-regulated the metallothionein gene in the livers of TAA-injected rats. Our results indicated that Arm exerted both in vitro and in vivo antifibrotic effects in rats, with inhibition of NF-κB, JunD and C/EBPß pathways.

Conophylline suppresses hepatic stellate cells and attenuates thioacetamide‐induced liver fibrosis in rats

“…We showed that CnP markedly reduced the fibrosis in the rat liver. Previous reports showed that liver fibrosis induced by CCl 4 or TAA was suppressed by armepavine (29), follistatin (30), salvianolic acids (31) and other agents (32)(33)(34)(35)(36)(37). Compared to these compounds, suppression of liver fibrosis by CnP was much more significant; indeed, the effect of CnP was visible on the surface of the liver.…”

Inhibitory Effect of Tanshinone IIA on Rat Hepatic Stellate Cells

“…After culturing for 24 hr, serum-starved cells were pretreated with Tan IIA (10 µM) or Sal B (200 µM) for 1 hr, then exposed to LPS for 15 min for harvesting NF-κB-p65 and MAPKs (ERK, JNK and p38), and exposed to LPS for 24 hr for harvesting α-SMA. Nuclear extracts of HSCs for NFκB-p65 translocation were prepared according to our previous study [29]. Whole cell protein extracts for measurement of ERK, JNK, p38 and α-SMA proteins were harvested with RIPA buffer.…”

A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera: Potential for Drug Development

“…In another study, armepavine from N. nucifera has been found to be effective against hepatic fibrosis induced by thioacetamide in rats. The treatment of armepavine inhibited protein expression of α-smooth muscle actin, collagen type I and angiopoietin-1, H 2 O 2 production and nuclear translocation of NF-κB, JunD and C/EBPβ in TNF-α stimulated hepatic stellate cells (HSC-T6) (Weng et al, 2012).…”

“…Grienke et al, 2015) 4 (s)-armepavine Auto-immune(Ka et al, 2010) (Liu et al, 2007), hepatic fibrosis(Weng et al, 2012), Cell cycle arrest(Liu et al, 2004), SLE(Liu et al, 2006), Anti-melanogenesis(Morikawa et al, 2016) 5 …”