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Context: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, can develop into metabolic associated fatty liver disease (MAFLD). Gypenosides (GP), the main phytochemical component of Gynostemma pentaphylla (Thunb.) Makino (Cucurbitaceae), have been applied for treatment of metabolic diseases. Objective: We investigate how GP modulate MAFLD-related hepatic steatosis and intestinal barrier injury. Materials and methods: In cell experiments, Caco-2 cells were treated with GP (150 or 200 lmol/L, 24 h), following lipopolysaccharide (LPS) exposure (10 lg/mL, 24 h) to mimic MAFLD in vitro. In in vivo experiments, control, model and modelþGP groups were set. High fructose diet/high fat (HFD/HF)-fed (12 weeks) MAFLD rats received GP treatment (300mg/kg, 6 weeks), followed by intra-peritoneal glucose tolerance test and histopathological examination of rat liver and intestinal mucosa using haematoxylin-eosin staining. Results: GP at 200 lM significantly reversed LPS-induced decreases in transepithelial electrical resistance (TER) value (25%), protein expression of occludin (two fold) and ZO-1 (four fold), and the ratio of p-AMPK to AMPK (five fold), while partially repressing LPS-induced leakage of FD4 (50%) and LPS-induced increases in the Toll-like receptor 4 (TLR4) level (50%) and the ratio of p-p65 to p65 (55%). Compared with the model rats, rats with GP treatment presented a reduction in gain of weight and glucose tolerance. In addition, GP alleviated HFD/HF-induced histopathological abnormalities in rat liver and intestinal mucosa. Conclusions: GP attenuates hepatic steatosis and intestinal barrier injury in MAFLD rats via the AMPK and TLR4/nuclear factor kappa B (NF-jB) pathways, providing a potential treatment for MAFLD patients. [ABSTRACT FROM AUTHOR]

Inflammation contributes to acute pulmonary embolism (APE). However, the contributions of the extracellular signal-regulated protein kinases (ERK) and phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signaling pathways have not yet been elucidated. The aim of this study was to examine the effects of aspirin on ERK and PI3K/Akt signaling in a rat model of APE and evaluate the prognostic values of brain natriuretic peptide (BNP), troponin (TnT) and D-Dimer. A total of 108 Sprague-Dawley rats were assigned into the control, sham, model and low-, medium- and high-dose aspirin (150, 300 and 600 mg/kg, respectively) groups. In each group, six rats were sacrificed 6, 24 and 72 h subsequent to the induction of APE to collect the lungs and serum. Western blot analysis was used to assess ERK, PI3K and Akt expression; enzyme-linked immunosorbent assay (ELISA) was used to analyze BNP, TnT and D-Dimer levels; and changes in lung pathology were evaluated using hematoxylin and eosin (H&E) staining. The results showed that ERK and PI3K levels were decreased in the control, sham and the three aspirin groups at all time-points compared with the model group (P<0.01). The exception was in the medium-dose aspirin group at 24 h. The serum levels of BNP, TnT and D-Dimer were lower in the control and sham groups at all time-points compared with the model group (P<0.05). Furthermore, the levels of BNP, TnT and D-Dimer levels were decreased in the aspirin-treated groups (P<0.05) and markedly increased in the model group (P<0.05) at 24 h compared with the levels at 6 h. Pulmonary embolism, alveolar wall necrosis and hemorrhage were observed in the model group 6, 24 and 72 h subsequent to the induction of the model. However, congestion and inflammation were attenuated following aspirin treatment. In conclusion, aspirin reduces lung damage and improves prognosis. Decreased ERK, PI3K and Akt expression in the lungs and reduced levels of BNP, TnT and D-Dimer may be important factors in the effects observed. [ABSTRACT FROM AUTHOR]