Total flavonoids extracted from Penthorum chinense Pursh inhibits oxidative stress and inflammation in liver cancer cells through the JAK2/STAT3 pathway.

BACKGROUND: Flavonoids are primary bioactive components of Penthorum chinense Pursh (PCP), which have anti-inflammatory and antioxidant effects. Previous studies have found that the pharmacological effect of PCP on liver cancer may be related to the inhibition of oxidative stress and inflammatory response in vivo. Based on the hepatoprotective effect of total flavonoids extracted from PCP (PCPTF), this study aimed to investigate the underlying mechanism by which PCPTF ameliorates liver cancer. METHODS: A nude mouse model of subcutaneous tumor formation of hepatocellular carcinoma was established. Following PCPTF treatment, the pathological changes, tumor cell proliferation and apoptosis, serum inflammatory factors and oxidative stress levels, and the levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) proteins in tumor tissues were detected. Lipopolysaccharides (LPS) was applied to construct liver cancer cell inflammation models in vitro. After treatment of PCPTF and JAK2 agonist coumermycin A1 (CA1) in the cells, protein levels, cell proliferation, inflammation, and oxidative stress were evaluated to explore the mechanism of PCPTF in improving liver cancer. RESULTS: In mice with liver cancer, PCPTF treatment inhibited tumor growth, improved the pathological changes, down-regulated interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), reactive oxygen species (ROS), up-regulated superoxide dismutase (SOD), and suppressed JAK2 and STAT3 phosphorylation. In liver cancer cells, PCPTF blocked the JAK2/STAT3 pathway, proliferation, and the release of inflammatory factors, regulated oxidative stress, and promoted apoptosis. However, CA1 reversed the effect of PCPTF on liver cancer cells. CONCLUSIONS: PCPTF suppresses the progression of liver cancer by ameliorating oxidative stress and inflammatory response, primarily through the regulation of the JAK2/STAT3 signaling pathway.