During the proliferation and metastasis, the tumor cells prefer glycolysis (Warburg effect), but its exact mechanism remains largely unknown. In this study, we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in the pathway of metabolic glycolysis. We observed a significant overexpression of PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1 expression and poor survival of hepatocellular carcinoma patients. Also, the depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis, indicating an oncogenic role of PGK1 in liver cancer progression. Further experiments showed that PGK1 played an important role in MYC-induced metabolic reprogramming, which led to an enhanced Warburg effect. Our results revealed a new effect of PGK1, which can provide a new treatment strategy for hepatocellular carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma (HCC).

The present study investigated the effects of berberine (BBR) on hepatic oxidative stress and the nuclear factor erythroid 2‑related factor 2/antioxidant response element (Nrf2/ARE) signalling pathway in rats in which non‑alcoholic fatty liver disease (NAFLD) was induced by a high‑fat diet. Rats were randomly divided into three groups: The normal control (NC), high‑fat diet (HFD) and BBR groups. The NC group received a normal diet, while the other two groups were fed a high‑fat diet. The rats in the BBR group were also fed BBR (100 mg/kg body weight) daily. A total of 8 weeks later, serum and liver lipid levels were measured. Hepatic histopathological changes were observed with haematoxylin and eosin and Oil Red O staining. Transmission electron microscopy was performed to observe the ultrastructural changes of the liver. The levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in the liver were measured. Quantitative polymerase chain reaction and western blotting were performed to investigate the expression of genes in the Nrf2/ARE signalling pathway in the liver. Histopathological results demonstrated that rats fed a high‑fat diet for 8 weeks developed NAFLD, characterized by hepatic steatosis. BBR significantly decreased the body weight and liver weight. BBR markedly reduced hepatic steatosis, and the serum and liver lipid levels. Hepatic SOD and GSH levels were increased, while MDA levels were decreased by BBR co‑administered with a high‑fat diet. Additionally, the Nrf2/ARE signalling pathway was revealed to be involved in the protective effect of BBR on rats fed a high‑fat diet. In conclusion, BBR may alleviate hepatic oxidative stress in rats with NAFLD, which may be partly attributed to the activation of the Nrf2/ARE signalling pathway.

The pathogenesis of non‐alcoholic fatty liver disease (NAFLD) is still not fully understood, and currently, no effective pharmacotherapy is available. Nuclear receptors (NRs) are important biological participants in NAFLD that exhibit great therapeutic potential. Chaihu Shugan powder (CSP) is a traditional Chinese medicine (TCM) formula that has a wide therapeutic spectrum including NAFLD, but the effective components and functional mechanisms of CSP are unclear. We adopted a network pharmacology approach using multiple databases for Gene Ontology (GO) enrichment analysis and the molecular complex detection (MCODE) method for a protein‐protein interaction (PPI) analysis, and we used molecular docking method to screen the NR targets and determine the corresponding CSP components. The screening results were validated through a NAFLD rat model that was used to explain the possible relationship between CSP and NAFLD. Finally, we screened PPARγ, FXR, PPARα, RARα and PPARδ as target genes and quercetin , kaempferol , naringenin , isorhamnetin and nobiletin as target compounds. The five components were detected through high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS), the results of which aligned with the docking experiments of PPARγ, PPARα and PPARδ. After CSP intervention, the NAFLD rat model showed ameliorated effects in terms of bodyweight, hepatic histopathology, and serum and liver lipids, and the mRNA levels of PPARγ, FXR, PPARα and RARα were significantly changed. The results from this study indicate that CSP exhibits healing effects in an NAFLD model and that the network pharmacology approach to screening NR targets and determining the corresponding CSP components is a practical strategy for explaining the mechanism by which CSP ameliorates NAFLD.

Shenling Baizhu San (SLBZS), a famous traditional Chinese medicine, has been demonstrated to exert protective effects against non-alcoholic fatty liver disease (NAFLD), but its exact mechanisms have not been well understood. The aim of this study was to investigate the mechanisms underlying the protective effects of SLBZS in a rat model of NAFLD using lipidomics and to evaluate the role of Sirtuin 1 (SIRT1) in the mechanism of SLBZS against NAFLD. The rat model of NAFLD was induced by high-fat feeding. An ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based untargeted lipidomics approach was applied to analyze hepatic lipid alterations, and the SIRT1-selective inhibitor EX 527 was used to inhibit SIRT expression in the liver. The results of body and biochemical parameters, as well as histological changes, indicated that SLBZS administration exerted protective effects against NAFLD. Lipidomic analysis showed that 30 lipid species were effectively regulated by SLBZS administration in rats fed a high-fat diet. Pathway analysis indicated that glycerophospholipid metabolism and glycerolipid metabolism were potential target pathways closely involved in the mechanism of SLBZS against NAFLD. Moreover, the beneficial effects of SLBZS on hepatic steatosis, some biochemical parameters and hepatic lipid species were partly diminished by SIRT1 inhibition. In conclusion, our results suggested that SLBZS administration could effectively alter some hepatic lipid species in rats fed a high-fat diet, which was mainly associated with the regulation of glycerophospholipid and glycerolipid metabolism. Furthermore, the beneficial effects of SLBZS on hepatic lipid metabolism may be at least partly attributed to SIRT1 activation in the liver.