Repurposing Artrestan (Sacubitril/Valsartan), unveiling its anti-inflammatory and fibrinolytic properties in ulcerative colitis in rats
نویسندگان
1 Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2 Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
4 Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
5 Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6 Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran
7 Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
8 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
doi
10.22038/ijbms.2025.87771.18964چکیده
Objective(s): Ulcerative colitis (UC) is an inflammatory disorder that is managed with various treatments, which have varying degrees of effectiveness and side effects, highlighting the need for new and more effective alternatives. In this study, we applied Artrestan (Sacubitrol/Valsartan), which has potent anti-inflammatory properties, alone or in combination with Mesalazine, in the treatment of UC animal models. Materials and Methods: Thirty male rats were randomly divided into control, colitis, Artrestan (60 mg/kg/day), Mesalazine (100 mg/kg/day), and Artrestan plus Mesalazine groups. UC was induced by intrarectal administration of acetic acid, followed by a 5-day course of oral medication, during which the disease activity index (DAI), including diarrhea, weight loss, and rectal bleeding, was assessed daily. Macroscopic and microscopic examinations, as well as assessments of oxidant-anti-oxidant, pro-inflammatory, and pro-fibrotic factors, were performed on colonic tissue. Results: Administration of Artrestan, especially in combination with Mesalazine, significantly decreased DAI and histological lesion scores in the microscopic assessment. Moreover, Artrestan modulated oxidant-anti-oxidant balance by increasing the activities of superoxide dismutase (SOD) and catalase (CAT) and reducing malondialdehyde (MDA) in colon tissue. Expression of inflammatory markers, including Interleukin 6 (IL-6) and Tumor necrosis factor-alpha (TNF-α), was decreased in the treated groups compared to the untreated group. Artrestan also attenuated fibrosis and collagen deposition in colon tissues, which was accompanied by a reduction in the expression of Transforming growth factor beta (TGF-β).Conclusion: Our findings suggest the therapeutic potential of Artrestan in combination with Mesalazine for the treatment of UC, as it modulates clinical symptoms, improves the oxidant-anti-oxidant balance, and reduces pro-inflammatory and pro-fibrotic factors, supporting further investigations in the clinical phase.
