18alpha-Glycyrrhizin induces apoptosis and suppresses activation of rat hepatic stellate cells

Abstract

SummaryBackgroundTo investigate the potential mechanisms underlying the protective effects of 18α Glycyrrhizin (GL) on rat hepatic stellate cells (HSCs) and hepatocytes in vivo and in vitro.Material/MethodsSprague-Dawley (SD) rats were randomly divided into 5 groups: normal control group, liver fibrosis group, high-dose 18α GL group (25 mg/kg/d), intermediate-dose 18α GL group (12.5 mg/kg/d) and low-dose 18α GL group (6.25 mg/kg/d). The rat liver fibrosis model was induced by carbon tetrachloride (CCl4). The expressions of α-smooth muscle actin (αSMA) and NF-κB were determined by real-time PCR and immunohistochemistry.Results18αGL dose-dependently inhibited the CCl4-induced liver fibrosis. There were significant differences in the mRNA and protein expressions of αSMA between the fibrosis group and 18α-GL treatment groups, suggesting that 18α GL can suppress the proliferation and activation of HSCs. Few HSCs were apoptotic in the portal area and fibrous septum in the liver fibrosis group. However, the double-color staining of a-SMA and TUNEL showed that 18α-GL treatment groups increased HSC apoptosis. NF-κB was mainly found in the nucleus in the fibrosis group, while cytoplasmic expression of NF-κB was noted in the 18αGL groups. In the in vitro experiments, 18α GL promoted the proliferation of hepatocytes, but inhibited that of HSCs. HSCs were arrested in the G2/M phase following 18α GL treatment and were largely apoptotic.Conclusions18α-GL can suppress the activation of HSCs and induce the apoptosis of HSCs by blocking the translocation of NF-κB into the nucleus, which plays an important role in the protective effect of 18α-GL on liver fibrosis.

Curcumol induces HSC-T6 cell death through suppression of Bcl-2: Involvement of PI3K and NF-κB pathways

“…The mitochondrial pathway of apoptosis is regulated by members of the Bcl-2 family, such as Bcl-2, Bcl-xL, and Bax (Qu et al, 2012). Novo et al have demonstrated that activated HSCs are resistant to most proapoptotic stimuli due to Bcl-2 overexpression, which may play a key role in the progression of fibrosis in chronic liver diseases (Novo et al, 2006).…”

MicroRNA-34a Promotes Hepatic Stellate Cell Activation via Targeting ACSL1

“…Although liver fibrosis is not malignant in and of itself, the process can destroy normal tissue structure and function and can gradually develop into cirrhosis, and eventually liver cancer. Hepatic stellate cells (HSCs) are vitamin A-storing pericytes found in the space of Disse [ 5 ]. Activation and proliferation of HSCs is pivotal to the development of liver fibrosis [ 4 , 6 , 7 ].…”

Glycyrrhizin regulates CD4+T cell response during liver fibrogenesis via JNK, ERK and PI3K/AKT pathway

“…18-β GL shows an antiviral activity against a great deal of DNA and RNA viruses due to potential activation of NF-κB and induction of IL-8 secretion [35]. 18-α GL is also reported to suppress the activation of HSCs and induce the apoptosis of HSCs by blocking the translocation of NF-κB to the nucleus [36]. However, abundant basic and clinical studies are still needed to further clarify pharmacological effects of GL, before it's included in the treatment of liver fibrosis.…”