Pinocembrin-7-O-β-d-glucoside (PCBG), pinocembrin (PCB), and 5-methoxy-pinocembrin-7-O-β-d-glucoside (MPG) are three flavonones isolated from Penthorum chinense Pursh (P. chinense). The effects of the three flavonones on hepatic steatosis and their molecular mechanisms in HepG2 cells were investigated in this study for the first time. A model of hepatic steatosis in HepG2 cells was induced by free fatty acid (FFA), and co-treated with the three flavonones as mentioned. Intracellular lipid droplets were detected by Oil Red O staining. PCB, PCBG, and MPG suppressed oxidative stress by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were ameliorated. Moreover, these flavonones enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of silent mating type information regulation 2 homolog 1 (SIRT1) and peroxisome proliferator-activated receptor α (PPARα), and reduced the expression of sterol regulatory element binding protein-1c (SREBP1c) and the downstream targets fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase 1 (SCD1). Molecular docking was used to predict the interaction and combination patterns between the three flavonones and the enzymes above. The results revealed that the SIRT1/AMPK pathway is involved in the functions of the three flavonones, and the most effective flavonone against hepatic steatosis might be PCBG, followed by MPG and PCB. Therefore, the three flavonones from P. chinense were found to exert preventive effects against hepatic steatosis by regulating the SIRT1/AMPK pathway.
Penthorum chinense Pursh. is a traditional Chinese herbal medicine used for the treatment of various ailments specially related to liver. Gansu Granule, the medicine made from the extract of P. chinense, has been widely used in the clinical setting. But the information about its active ingredients is lacking. In this paper, the extract of P. chinense was analyzed by high performance liquid chromatography with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Among the 27 compounds that were identified based on their mass spectrometry data, ten were reported for the first time from P. chinense. Chromatographic fingerprints generated by high-performance liquid chromatography by analyzing 21 batches of P. chinense, displayed six common peaks. Finally, four major compounds were identified namely; gallic acid, brevifolin carboxylic acid, 2,6-dihydroxyacetophenone-4-O-β-D-glucoside, and pinocembrin-7-O-β-D-glucoside. The average content of each compound was 24.58, 109.6, 15.52, and 18.81 mg/g, respectively. In addition, this study also suggests that the qualitative liquid chromatography with mass spectrometry and the quantitative high-performance liquid chromatography analytical methods using monolithic columns are simple, rapid, accurate, and reproducible and have the potential to be used for the comprehensive quality control of P. chinense.
We aimed to further investigate mitochondrial adaptations to muscle disuse and the consequent metabolic disorders. Male rats were submitted to hindlimb unloading (HU) for three weeks. Interestingly, HU increased insulin sensitivity index (ISI) and decreased blood level of triglyceride and insulin. In skeletal muscle, HU decreased expression of pyruvate dehydrogenase kinase 4 (PDK4) and its protein level in mitochondria. HU decreased mtDNA content and mitochondrial biogenesis biomarkers. Dynamin-related protein (Drp1) in mitochondria and Mfn2 mRNA level were decreased significantly by HU. Our findings provide more extensive insight into mitochondrial adaptations to muscle disuse, involving the shift of fuel utilization towards glucose, the decreased mitochondrial biogenesis and the distorted mitochondrial dynamics.
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