Curcumae Ameliorates Diethylnitrosamine-Induced Hepatocellular Carcinoma via Alteration of Oxidative Stress, Inflammation and Gut Microbiota
Yunyan Zhang, Xuelian Li, Xinghua Li
Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) increased the risk factor of hepatocellular carcinoma (HCC). NAFLD induces the hepatic-related cancer deaths mostly in middle-aged men. NAFLD enhanced the inflammatory reaction and oxidative stress in the hepatic tissue. Curcumae exhibited the anti-inflammatory and antioxidant effects. In this study, we made an attempt to scrutinize the protective effect of curcumae on obesity-induced HCC via alteration of inflammation, oxidative stress and gut microbiota. Methods: The rats used in this experiment were Wistar rats, 100 mg/kg intraperitoneal injection of diethylnitrosamine (hepatic carcinogen) was used at 2 weeks. After 6 weeks of the experimental study, the rats were randomly divided into high-fat diet (HFD) with or without curcumae-treated group rats and received the treatment for 22 weeks. Hepatic, non-hepatic, cardiac, antioxidant, pro-inflammatory and inflammatory were estimated at the end of the study. The stools of the experimental rats were collected for estimating the gut microbiota. Results: Curcumae-treated group rats exposed reduction of the hepatic nodules in hepatic tissue. Curcumae significantly (P< 0.001) diminished the level of hepatic parameters and antioxidant parameters in the serum. Curcumae significantly (P< 0.001) suppressed the pro-inflammatory cytokines level, viz. interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-7 (IL-7) and augmented the level of interleukin-10 (IL-10) in the serum and hepatic tissue. Curcumae significantly (P< 0.001) suppressed inflammatory mediators including cyclooxygenase (COX-2), prostaglandin E2 (PGE2) and nuclear factor kappa B (NF-κB) in the serum and hepatic tissue. Furthermore, curcumae increased the gut microbial diversity and richness and decreased the relative abundance of genus Mucispirillum and Clostridium , respectively. Conclusion: Curcumae prevents HFD-induced inflammation during the hepatic carcinoma by modulating the oxidative stress, inflammatory reaction and gut microbiota. Keywords: curcumae, hepatic cellular carcinoma, gut microbiota, inflammation, antioxidant