Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism

BACKGROUND Liver fibrosis is a formidable global medical challenge,with no effective clinical treatment currently available.Yinhuang granule(YHG)is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos.It is frequently used for upper respiratory tract infections,pharyngitis,as well as acute and chronic tonsillitis.AIM To investigate the potential of YHG in alleviating carbon tetrachloride(CCl4)-induced liver fibrosis in mice.METHODS To induce a hepatic fibrosis model in mice,this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk.Meanwhile,liver fibrosis mice in the low dose of YHG(0.4 g/kg)and high dose of YHG(0.8 g/kg)groups were orally administered YHG once a day for 4 wk.Serum alanine/aspartate aminotransferase(ALT/AST)activity and liver hydroxyproline content were detected.Sirius red and Masson's trichrome staining assay were conducted.Realtime polymerase chain reaction,western-blot and enzyme-linked immunosorbent assay were conducted.Liver glutathione content,superoxide dismutase activity level,reactive oxygen species and protein carbonylation amount were detected.RESULTS The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice,as reflected by decreased serum ALT/AST activity and improved liver histological evaluation.YHG also attenuated liver fibrosis,evident through reduced liver hydroxyproline content,improvements in Sirius red and Masson's trichrome staining,and lowered serum hyaluronic acid levels.Furthermore,YHG hindered the activation of hepatic stellate cells(HSCs)and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice.YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2(Nrf2)and upregulated the expression of Nrf2-dependent downstream antioxidant genes.In addition,YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice,as demonstrated by increased liver adenosine triphosphate content,mitochondrial DNA levels,and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1.CONCLUSION YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs,reducing inflammation,alleviating liver oxidative stress damage through Nrf2 activation,and promoting liver mitochondrial biogenesis.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer,characterized by excessive deposition of the extracellular matrix.In the past,hepatic fibrosis was thought to be a static and irreversible pathological process.In recent years,with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level,more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process.Therefore,it is particularly important to find an effective,simple,and inexpensive method for its prevention and treatment.Traditional Chinese medicine(TCM)occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions,low cost,and multi-target effectiveness.A large number of research results have shown that TCM monomers,single herbal extracts,and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis.Oxidative stress(OS)is one of the key factors in the occurrence and development of hepatic fibrosis.Therefore,this article reviews the progress in the understanding of the mechanisms of TCM monomers,single herbal extracts,and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years,in order to provide a reference and basis for drug therapy of hepatic fibrosis.

Sodium selenite ameliorates dextran sulfate sodiuminduced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+)CD25(+) regulatory T-cell responses

AIM To assess the effect of sodium selenite on the severity of dextran sulfate sodium(DSS)-induced colitis in C57BL/6 mice.METHODS Mice were randomly divided into four groups(n = 10/group): normal group, selenium(Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes(LPL) of the colon, the expression of m RNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured.RESULTS Se significantly ameliorated the symptoms of colitis and histological injury(P < 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells(P < 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL(P < 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17 A, IL-21, T-bet, and RORγt(P < 0.05 each), but enhanced the expression of IL-10 and Foxp3(P < 0.05 each). CONCLUSION These results suggest that Se protects against DSSinduced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells.

Comparison of smoothness-constrained and geostatistically based cross-borehole electrical resistivity tomography for characterization of solute tracer plumes

Experiments using electrical resistivity tomography(ERT) have shown promising results in reducing the uncertainty of solute plume characteristics related to estimates based on the analysis of local point measurements only.To explore the similarities and differences between two cross-borehole ERT inversion approaches for characterizing salt tracer plumes,namely the classical smoothness-constrained inversion and a geostatistically based approach,we performed two-dimensional synthetic experiments.Simplifying assumptions about the solute transport model and the electrical forward and inverse model allowed us to study the sensitivity of the ERT inversion approaches towards a variety of basic conditions,including the number of boreholes,measurement schemes,contrast between the plume and background electrical conductivity,use of a priori knowledge,and point conditioning.The results show that geostatistically based and smoothness-constrained inversions of electrical resistance data yield plume characteristics of similar quality,which can be further improved when point measurements are incorporated and advantageous measurement schemes are chosen.As expected,an increased number of boreholes included in the ERT measurement layout can highly improve the quality of inferred plume characteristics,while in this case the benefits of point conditioning and advantageous measurement schemes diminish.Both ERT inversion approaches are similarly sensitive to the noise level of the data and the contrast between the solute plume and background electrical conductivity,and robust with regard to biased input parameters,such as mean concentration,variance,and correlation length of the plume.Although sophisticated inversion schemes have recently become available,in which flow and transport as well as electrical forward models are coupled,these schemes effectively rely on a relatively simple geometrical parameterization of the hydrogeological model.Therefore,we believe that standard uncoupled ERT inverse approaches,like the ones discussed and assessed in this paper,will continue to be important to the imaging and characterization of solute plumes in many real-world applications.