Curcumae Ameliorates Diethylnitrosamine-Induced Hepatocellular Carcinoma via Alteration of Oxidative Stress, Inflammation and Gut Microbiota

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, nonhepatic, 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 proinflammatory 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.

Redefining the hepatoprotective potential of Javanese turmeric (Curcuma xanthorrhiza) Kombucha towards the diethylnitrosamine-induced hepatotoxicity of mice

“…, 2019). These free radicals increased lipid peroxidation, suppressed antioxidant enzyme activity and increased the number of toxic metabolites such as 4-hydroxynonenal and MDA (Zhang et al. , 2021).…”

“…DEN was metabolized in the liver by P450 monooxygenase, resulting in active ethyl radicals (Mansour et al, 2019). These free radicals increased lipid peroxidation, suppressed antioxidant enzyme activity and increased the number of toxic metabolites such as 4-hydroxynonenal and MDA (Zhang et al, 2021).…”

“…Patients with early stages could undergo transplantation, abrasion or resection. However, symptoms may be hard to detect during the early stages and can lead to delayed treatment (Zhang et al, 2021). Therefore, prevention is needed at the early stages to ease the burden and arrest the expansion of the disease.…”

“…Patients with early stages could undergo transplantation, abrasion or resection. However, symptoms may be hard to detect during the early stages and can lead to delayed treatment (Zhang et al. , 2021).…”

Effect and Mechanism of Schizandrin A in the Treatment of Liver Cancer Using Network Pharmacology, Molecular Docking, and Target Validation

“…It has been reported that the levels of IL-6, TNF-α, and IL-1β in mouse serum with liver cancer are significantly higher than those in normal mice and are positively correlated with the degree of malignancy of the tumors. 27,28 Therefore, they can be used as important indicators for screening and evaluating the prognosis of liver cancer. Cell experimental results in vitro showed that SA could significantly reduce the levels of inflammatory factors (TNF-α, IL-6, IL-1β, and IFN) in HepG2 cells and increase the levels of anti-inflammatory factors (IL-10), with statistical significance ( P < .05), which was mutually supported by the results of network pharmacology.…”