Chlorogenic acid attenuates 5-fluorouracil-induced intestinal mucositis in mice through SIRT1 signaling-mediated oxidative stress and inflammatory pathways

Mucositis, a common side effect of the chemotherapeutic drug 5-Fluorouracil (5-FU), causes severe and aggravating effects on mucosal cells in the oral cavity and intestine. This study in mice aimed to assess the antioxidant, anti-inflammatory, and mucosal protective properties of chlorogenic acid in mitigating 5-FU-induced intestinal mucositis. To investigate these potential protective effects, we developed a mouse model by administering an initial intraperitoneal (i.p.) injection of 5-FU, followed by daily i.p. injections of chlorogenic acid (10 and 20 mg/kg) for 10 consecutive days. Chlorogenic acid mitigated intestinal histopathological damage, reduced proinflammatory mediators and malondialdehyde (MDA) levels, and increased the glutathione (GSH) level by 5-FU. Chlorogenic acid treatment led to a significant reduction in the expression of inflammation-related proteins decreased oxidative stress-related proteins and, attenuated the expression of apoptosis and autophagy-related proteins in small intestinal tissues. Additional investigations are necessary to verify our findings and enhance our comprehension of how SIRT1 inhibition (EX-527) counteracts the anti-inflammatory effects of chlorogenic acid in intestinal tissues. In conclusion, our mice study has shown that chlorogenic acid exerts its protective effects on 5-FU-induced intestinal tissue damage, by reducing oxidative stress and inflammation through the modulation of multiple signaling pathways, including the TLR4/NF-κB/MAPK, AMPK/ SIRT1, and PI3K/AKT axis. These findings highlight the potential of chlorogenic acid as a therapeutic agent for mucositis, given its anti-inflammatory and antioxidant properties.