Physalin B ameliorates nonalcoholic steatohepatitis by stimulating autophagy and NRF2 activation mediated improvement in oxidative stress.

Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease that may ultimately lead to cirrhosis and liver cancer, and there are few therapeutic options for its treatment. Physalin B (PB), a withanolide isolated from Physalis species (Solanaceae), exhibits a broad spectrum of biological activities, however, the potential role of PB in NASH has not been evaluated. The present study investigated the protective effects of PB against NASH and further elucidated the mechanisms of PB in hepatic autophagy and oxidative stress in vitro and in vivo. We conducted a series of experiments using methionine-choline deficient (MCD) diet induced NASH mice and cultured L02 cells. Serum markers of liver injury, morphology, and the histology of liver tissues were investigated. Western blot assays and quantitative real-time PCR were used to investigate the hepatoprotective effect of PB. PB significantly ameliorated hepatic injury, including hepatic index, transaminase activities, histology, and inflammation in MCD-induced mice. Moreover, PB markedly increased the expression of P62 and the ratio of LC3Ⅱ/Ⅰ in vitro and in vivo. Furthermore, PB promoted the interaction between endogenous KEAP1 and P62, reduced the interaction between KEAP1 and NRF2, activated the nuclear translocation of NRF2 and NRF2 target gene expression, and ultimately attenuated oxidative stress. In addition, knockdown of P62 blocked PB-mediated activation of NRF2 in L02 cells. These results clearly indicated that PB ameliorated NASH by stimulating autophagy and P62-KEAP1-NRF2 antioxidative signaling, suggesting that PB is expected to become a novel therapeutic drug for NASH.

Large rectification magnetoresistance in nonmagnetic Al/Ge/Al heterojunctions.

Magnetoresistance and rectification are two fundamental physical properties of heterojunctions and respectively have wide applications in spintronics devices. Being different from the well known various magnetoresistance effects, here we report a brand new large magnetoresistance that can be regarded as rectification magnetoresistance: the application of a pure small sinusoidal alternating-current to the nonmagnetic Al/Ge Schottky heterojunctions can generate a significant direct-current voltage, and this rectification voltage strongly varies with the external magnetic field. We find that the rectification magnetoresistance in Al/Ge Schottky heterojunctions is as large as 250% at room temperature, which is greatly enhanced as compared with the conventional magnetoresistance of 70%. The findings of rectification magnetoresistance open the way to the new nonmagnetic Ge-based spintronics devices of large rectification magnetoresistance at ambient temperature under the alternating-current due to the simultaneous implementation of the rectification and magnetoresistance in the same devices.