Emodin, a natural anthraquinone, may help protect gastrointestinal health during chemotherapy treatment by decreasing inflammation of the gastric mucosa and preserving gut morphology

Abstract

The clinical utility of 5‐fluorouracil (5FU) chemotherapy remains hampered by hematopoietic and gastrointestinal toxicities. Emodin, a natural anthraquinone, has been shown to have anti‐inflammatory potential and may be effective as a complementary therapeutic used during chemotherapy treatments. The purpose of this study was to evaluate the efficacy of emodin on reducing the non‐specific toxicities associated with 5FU treatment. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n=5), Control + Emodin (n=5), 5FU + Vehicle (n=20), 5FU + Emodin (n=20). 5FU was administered via I.P. over 3 cycles of the following regime: 5 consecutive days of 5FU at 35mg/kg followed by 9 days of recovery. Emodin was administered via oral gavage 3x/week at 40mg/kg through the entire 3 cycles of 5FU treatment. 5FU + Emodin treated mice showed improved muscular strength (p<0.05), fun‐to‐fatigue time (P<0.05), and peripheral nociception (p<0.05) compared to 5FU + Vehicle treated mice. 5FU + Emodin treated mice did not show recovery of decreased circulating immune cells and red blood cells that is common with 5FU treatment. 5FU + Vehicle treated mice did show slightly increased splenic CD11b+ F4/80+ macrophages (6.8%) vs. control mice (4.3%), a phenotype that was not decreased in 5FU + Emodin treated mice (6.5%). 5FU treatment shows classic inflammatory damage to the gastric mucosa. 5FU + Vehicle treated mice show decreased villus length (p<0.05) compared to control mice. 5FU + Emodin treated mice showed increased villus length (p<0.05) compared to 5FU + Vehicle treated mice but remained shorter (p<0.05) than control mice. Further, small intestine tissue shows increased TNFα expression in 5FU + Vehicle treated mice which was decreased (p<0.05) in 5FU + Emodin treated mice. Similar increases in inflammatory gene expression are seen in the colon tissue of 5FU + Vehicle treated mice. 5FU + Emodin treated mice show decreased colonic TNFα expression (p<0.05) and trending decrease in MCP‐1 (p=0.052) and NOS2 (p=0.065) expression compared to 5FU + Vehicle treated mice. Taken together, Emodin treatment may contribute to improved GI health by reducing damaging inflammation which may contribute to improved overall quality of life. Future analysis will expand on the inflammatory signaling pathways involved in emodin signaling and will investigate the potential role of the gut microbiome in reducing GI inflammation in this model of 5FU treatment.Support or Funding Information1F31AT009820 to ATS.1RO1CA218578 to EAM. 1R41AT009964 to EAM. 5R21CA191966 to EAM.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.