ABSTRACT
Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.
ABSTRACT
OBJECTIVE: To prepare and develop a GDH-2 air sampling tube for detecting 12 kinds of chlorobenzenes(CBs) in workplace air and to establish a matching detecting method. METHODS: The self-developed GDH-2 air sampling tube was filled with ion exchange resin and activated carbon, and the mass ratio was 10 ∶1. The GDH-2 air sampling tube was used to collect 12 kinds of CBs with coexistence of gaseous and aerosol in the air. After elution with toluene, they were separated on a chromatographic column and determined by microcell electron capture detector. RESULTS: The quantitative detecting range of the method was 0.51×10~(-3)-6 000.00 mg/L, with the correlation coefficients greater than 0.999 4. The minimum detection concentration was 0.02-61.99 μg/m~3, and the minimum quantitative concentration was 0.05-206.62 μg/m~3. The average desorption efficiency was 90.8%-104.0%. The within-run relative standard deviation(RSD) was 1.0%-5.7%, and the between-run RSD was 3.0%-7.3%. The samples can be stored at room temperature for at least 26 days. CONCLUSION: The self-developed GDH-2 air sampling tube and its matching measuring method can be used for the collection and determination of the 12 kinds of CBs in the air of workplace.