Magnesium isoglycyrrhizinate promotes the activated hepatic stellate cells apoptosis via endoplasmic reticulum stress and ameliorates fibrogenesis in vitro and in vivo

Abstract

Varied pathogenetic elements have been touched upon the liver fibrosis, including inflammatory, stress, apoptosis and unfolded proteins aggregation. Magnesium Isoglycyrrhizinate (MgIG) has been accepted to be a neuroprotective effect, hepatoprotective and anti-inflammatory molecule. In our vitro researches, MgIG was considered to activate hepatic stellate cells (HSCs) apoptosis by promoting endoplasmic reticulum stress (ERS) detrimental response to a certain extent. Consequently, MgIG showed its potential therapeutic capacity in fibrogenesis and counteracted the pathogenetic aspects, which were involved in integrating current treatments correcting liver fibrosis. In addition, we further verificated the behavior and pathogenic mechanisms in the CCl -induced liver fibrosis in male mice. What surprised us was that with the treatment of MgIG caused the activation of ERS and resisted the activated HSCs in the protective effects on liver damage. We found MgIG significantly promoted the apoptosis of activated HSCs and protected the CCl -induced liver fibrosis. Main molecules came down to the unfolded protein response signaling pathway. Furthermore, MgIG inhibited the levels of the downstream inflammatory cytokines, which were triggered by CCl -induced liver fibrosis. Here, we reported that MgIG improved behavioral impairments induced by intraperitoneal injection of CCl and decreased the expression of proinflammatory factor, which indicated the preserving effects on liver fibrosis. © 2017 BioFactors, 43(6):836-846, 2017.

A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

“…TRIzol reagent was used to extract A2780 RNA according to the protocol. Real‐time PCR was executed by 7500 RT‐PCR system as described previously . The mRNA levels of the target genes were calculated and results are from triplicate experiments.…”

Magnesium Isoglycyrrhizinate Ameliorates Fibrosis and Disrupts TGF-β-Mediated SMAD Pathway in Activated Hepatic Stellate Cell Line LX2

“…Cellular senescence is defined as the lack of proliferative potential in cells with irreversible cell cycle status ( Kuilman et al, 2010 ; van Deursen, 2014 ; Fridlyanskaya et al, 2015 ). Since MgIG was previously known for its anti-proliferative effect on HSCs ( Bian et al, 2017 ), we queried if the cells could have acquired replicative senescence. Consistent with Bian et al (2017) , p27 protein expression was found to be increased with MgIG treatment ( Figure 4A ).…”

“…Since MgIG was previously known for its anti-proliferative effect on HSCs ( Bian et al, 2017 ), we queried if the cells could have acquired replicative senescence. Consistent with Bian et al (2017) , p27 protein expression was found to be increased with MgIG treatment ( Figure 4A ). However, the increase in p27 was only observable at shorter duration of 24 h, suggesting that senescence is an early process acquired by the cells upon exposure to MgIG.…”

“…Conversely, there is a lack of studies with direct focus on the effect of MgIG on the microenvironment of liver fibrosis, particularly on the HSCs. Recently, Bian et al (2017) have reported that MgIG induced cell cycle arrest and promoted apoptosis in HSC-T6 cells. In addition, they have shown that MgIG could alleviate liver fibrotic injury via the activation of endoplasmic reticulum stress signaling pathway.…”

Dihydroartemisinin attenuates alcoholic fatty liver through regulation of lipin‐1 signaling

“…Induction of ER stress and activation of mitochondrial pathways are considered to be the key mechanisms underlying hepatocyte lipoapoptosis . In the present study, we mainly addressed the role of two major protein isoforms of lipin‐1 in the inhibition of steatosis and lipoapoptosis by DHA.…”