22 December 2011
18alpha-Glycyrrhizin induces apoptosis and suppresses activation of rat hepatic stellate cells
Ying QuBCE, Wei-Hua ChenB, Lei ZongD, Ming-Yi XuF, Lun-Gen LuAGDOI: 10.12659/MSM.882196
Med Sci Monit 2012; 18(1): BR24-32
Abstract
Background: To investigate the potential mechanisms underlying the protective effects of 18alpha Glycyrrhizin (GL) on rat hepatic stellate cells (HSCs) and hepatocytes in vivo and in vitro.
Material/Methods: Sprague-Dawley (SD) rats were randomly divided into 5 groups: normal control group, liver fibrosis group, high-dose 18alpha GL group (25 mg/ kg/d), intermediate-dose 18alpha GL group (12.5 mg/kg/d) and low-dose 18alpha GL group (6.25 mg/ kg/d). The rat liver fibrosis model was induced by carbon tetrachloride (CCl4). The expressions of alpha-smooth muscle actin (alphaSMA) and NF-kappaB were determined by real-time PCR and immunohistochemistry.
Results: 18alphaGL dose-dependently inhibited the CCl4-induced liver fibrosis. There were significant differences in the mRNA and protein expressions of alphaSMA between the fibrosis group and 18alpha-GL treatment groups, suggesting that 18alpha 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 18alpha-GL treatment groups increased HSC apoptosis. NF-kappaB was mainly found in the nucleus in the fibrosis group, while cytoplasmic expression of NF-kappaB was noted in the 18alphaGL groups. In the in vitro experiments, 18alpha GL promoted the proliferation of hepatocytes, but inhibited that of HSCs. HSCs were arrested in the G2/M phase following 18alpha GL treatment and were largely apoptotic.
Conclusions: 18alpha-GL can suppress the activation of HSCs and induce the apoptosis of HSCs by blocking the translocation of NF-kappaB into the nucleus, which plays an important role in the protective effect of 18alpha-GL on liver fibrosis.
Keywords: Liver Cirrhosis - drug therapy, In Situ Nick-End Labeling, Hepatic Stellate Cells - drug effects, Glycyrrhizic Acid - therapeutic use, Dose-Response Relationship, Drug, Cell Proliferation - drug effects, Carbon Tetrachloride - toxicity, Real-Time Polymerase Chain Reaction
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
08 Mar 2024 : Laboratory Research
Evaluation of Retentive Strength of 50 Endodontically-Treated Single-Rooted Mandibular Second Premolars Res...Med Sci Monit In Press; DOI: 10.12659/MSM.944110
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952