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, 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

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

All the experimental protocols were approved from the First People’s Hospital of Lianyungang City. All the protocols are carried out in accordance with the Institute guidelines.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All the authors declare no conflicts of interest in this work.

Additional information

Funding

The current experimental study was self-funded.