Tehran University of Medical Sciences Traditional and Integrative Medicine 2476-5104 6 3 2021 09 19 216 228 Mahtab Mohammadifard Department of Pathology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran Hossein Javdani Department of Molecular Medicine, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran Ghazaleh Khalili-Tanha Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran Ali Farahi Department of Molecular Medicine, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran Mohsen Foadoddini Department of Physiology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran Mehran Hosseini Cellular and Molecular Research Center Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran 2021 04 08 2021 06 14 Saffron (Crocus sativus L.) has long been considered a medicinal plant in Traditional Persian Medicine (TPM) due to its therapeutic properties. Despite this interest, its effects on gastrointestinal disorders have not been completely taken into consideration. Hence, this study aimed to evaluate the pharmacological activity of ethanolic extracts of saffron stigma (SS) and saffron petal (SP) in acetic acid-induced gastric ulcer in rats. The gastric ulcer model was imitated by the serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed with 100 mg/kg and 200 mg/kg of ethanolic extracts of SS or SP, omeprazole (40 mg/kg), or saline for 12 days. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. The highest anti-ulcer activity was observed in the omeprazole-treated animals with the lowest ulcer size (4.29 ± 1.78 mm2). SS could not reduce gastric ulcer size in rats. Compared to the untreated rats, SP treatment significantly decreased ulcer indices in a dose-dependent manner. The gastric levels of PGE2, VEGF, and MDA were significantly elevated in the untreated animals with gastric ulcers compared to rats in the control group. The SS extract suppressed the elevated PGE2 and VEGF levels at both doses, while SP did not have a significant influence. Both SS and SP treatments significantly ameliorated MDA levels in rats with gastric ulcers. Omeprazole treatment enhanced the PGE2 level and suppressed MDA contents, but it did not influence the VEGF level. In conclusion, our findings demonstrated that the saffron stigma has no significant effects on the gastric ulcer healing process, while its petals accelerate the process. This discrepancy can be attributed to the difference in the main secondary metabolites between saffron stigma and petals. https://jtim.tums.ac.ir/index.php/jtim/article/view/377