Nickan Research Institute Immunopathologia Persa 2423-8015 12 1 2026 01 01 Protective effects of Achillea millefolium on 5-fluorouracil-induced intestinal mucositis in a Wistar rat model e43922 e43922 10.34172/ipp.2025.43922 EN Amirabbas Gharibi https://orcid.org/0009-0001-6388-9906 Atefeh Ashtari https://orcid.org/0000-0001-8799-2417 Firoozeh Niazvand https://orcid.org/0000-0002-7929-4819 Narges Chamkouri https://orcid.org/0000-0003-1693-4505 Asma Mohammadi https://orcid.org/0000-0002-4238-5426 Nahid Moradi Gharibvandi https://orcid.org/0000-0003-3237-5520 Journal Article 10.34172/ipp.2025.43922 2025 05 09 2025 09 02 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.