The effect of acetylsalicylic acid and pentoxifylline in guinea pigs with non-alcoholic steatohepatitis.

Therapeutic options are urgently needed for non-alcoholic fatty liver disease (NAFLD), but development is time-consuming and costly. In contrast, drug repurposing offers the advantages of re-applying compounds that are already approved, thereby reducing cost. Acetylsalicylic acid (ASA) and pentoxifylline (PTX) have shown promise for treatment of NAFLD, but have not yet been tested in combination. Guinea pigs were fed a high-fat diet for 16 weeks and then continued on the diet while being treated with ASA, PTX or ASA+PTX for 8 weeks. Chow-fed animals served as healthy controls. Guinea pigs were CT scanned before intervention start and at intervention end. Animals without steatosis (ie NAFLD) at week 16 were excluded from the data analysis. ASA and PTX alone or in combination did not improve hepatic steatosis, ballooning, inflammation or fibrosis nor did the treatments affect liver enzymes (aminotransferases and alkaline phosphatase) or circulating lipids. Liver triglyceride levels, relative liver weight and hepatic mRNA expression of monocyte chemoattractant protein 1, interleukin 8 and platelet-derived growth factor b were nominally decreased. Thus, in the current study, treatment with ASA and PTX alone or in combination for 8 weeks did not ameliorate NASH or hepatic fibrosis in guinea pigs.

Investigation of antidiabetic potential of Phyllanthus niruri L. using assays for α-glucosidase, muscle glucose transport, liver glucose production, and adipogenesis.

Phyllanthus niruri is used in herbal medicine for treatment of diabetes. The objective of this study was to investigate the antidiabetic potential of P. niruri, using assays for α-glucosidase, muscle glucose transport, liver glucose production and adipogenesis. α-Glucosidase inhibitory activity was performed on aqueous and ethanolic extract of aerial parts of P. niruri. The aqueous and ethanolic extract of P. niruri showed α-glucosidase inhibitory activity with IC50 values of 3.7 ± 1.1 and 6.3 ± 4.8 µg/mL, respectively. HR-bioassay/HPLC-HRMS and NMR analysis was used for identification of compounds. Corilagin (1) and repandusinic acid A (2) were identified as α-glucosidase inhibitors in the water extract of P. niruri with IC50 values of 0.9 ± 0.1 and 1.9 ± 0.02 µM, respectively. In in vitro cell-based bioassays, cells were treated for 18 h with maximal non-toxic concentrations of the ethanolic extract of P. niruri, which were determined by the lactate dehydrogenase cytotoxicity assay. The ethanolic extract of P. niruri was not able to reduce glucose-6-phosphatase activity. However, the extract increased deoxyglucose uptake in C2C12 muscle cells and enhanced adipogenesis in 3T3-L1 fat cells which has been reported for the first time. The present study demonstrated that P. niruri may thus have potential application for treatment and/or management of type 2 diabetes.