Cancer is a group of diseases that include uncontrolled cell division and cell migration, as well as resistance to cell death

Introduction: Cancer remains a major global health concern, with chemotherapy being a cornerstone of treatment. However, chemotherapy drugs, such as 5-fluorouracil (5-FU), are associated with severe side effects, including intestinal mucositis. Achillea millefolium, a medicinal plant with established anti-inflammatory and antioxidant properties, has been suggested as a potential protective agent against chemotherapy-induced toxicities. Objectives: This study aims to investigate the ameliorative effects of A. millefolium on 5-FU-induced intestinal mucositis. Materials and Methods: A total of 28 male Wistar rats were randomly assigned to four groups (n = 7/group). Group 1 (control) received normal saline by gavage for nine days. Group 2 received a single intraperitoneal injection of 5-FU (150 mg/kg) on day five. Group 3 was administered A. millefolium extract (250 mg/kg, gavage) for nine consecutive days. Group 4 received both A. millefolium extract (250 mg/kg, gavage) and a single intraperitoneal injection of 5-FU. The villus-to-crypt ratio, superoxide dismutase (SOD) activity, and catalase (CAT) levels were evaluated. Results: Our study showed, 5-FU administration led to significant oxidative stress and severe intestinal mucosal damage. Body weight loss was pronounced in the 5-FU/saline group. Co-administration of A. millefolium extract with 5-FU significantly reduced oxidative stress, enhanced SOD activity, and improved the villus-to-crypt ratio compared to the 5-FU group. Conclusion: The findings indicated that A. millefolium possesses protective effects against 5-FU-induced intestinal mucositis. These results suggest its potential role in mitigating chemotherapy-related side effects and enhancing patient outcomes.